Archives of neurology and psychiatry from the Pathological Laboratory of the London County Asylums 4.1909

ARCHIVES OF NEUROLOGY

11

ANl> PSYCHIATRY

THE PATHOLOGICAL LABORATORV

LONDON COUNTY ASYLUMS
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ARCHIVES OF NEUROLOGY

AND PSYCHIATRY

Introducturif Paper bij Dr. llenri/ Mandslci/).

FKOM TJIK

PATHOLOGICAL LABORATORY

OK THE

LONDON COUNTY ASYLUMS,

CLAYIUJIIY, KSSEX.

ia)ITKI) BY

FREDERICK WALKER MOTT, M.l)., F.R.S., F.R.C.l\,

Direrior of the Jjahandonj a/ud J^otholot/lst to the Ijoiuttni CiniD fif Asi/hnns;
Plufsirian toChonnij Cross Jlospital; Fnllervin. Vrofessitr, Uitijiil ivslitution ;
CorrespoiuliiKj Memher of the Soeiete de Vsifchiatrie de Paris;

Forciyn. Associate of the i^ociete Clfniyv.e de Mrdcciito Menlale.

VOL. IV.—1909.

Pkinti;!) foi: tiik LONDON COUNTY COUNCIL,

And may be jnirtdiased, eitlier directly or through any Bookseller, from

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^{(fCiifs for the S(de iJtr I*tdtUrtiiinns nf the Jjomhni (■(ojuty (Uoim d,

1 -

PREFACE.

lx tlie preiace of volume 111. of tlie Aicliives of Neurology 1
veutuied to express a liope tliat the London County Council at some
future date would establisli in London an acute hospital for the investi¬
gation and treatment of cui-able mental cases. I also pointed out that
witli the establishment of such a hospital a psychiatrical clinic might be
looked for, on the basis of the Munich institution with its associated
laboratories for clinical and pathological research. The Asylums Com¬
mittee has long been in sympathy with the removal of the l^athological
Laboratory to a more central situation, w^hereby it could be utilized not
only by all the olhcers in the service if they so desired, but also by
students and medical practitioners interested in the study of brain
diseases. The piesent laboratory, although admirably equipped, is so
far distant that it is not available to the majority of the officers and
students interested in the study of the pathology of mental diseases.
Economic reasons doubtless prevented the Council from giving effect
to a recommendation of the Pathological Sub-Committee of the
desirability of removing the laboratory to London. The London County
Council having accepted the munificent donation of Ur. Henry Maudsley,
there is every reason to hope that a hospital for the treatment and
study of acute mental diseases with a psychiatrical clinic and associate<l
pathological and clinical laboratories will now^ be established in London.

In that same preface I further sUited that if suitable post-graduate
training in medico-psychology and nemo-pathology were established,
doubtless the Universities and licensing bodies might be induced to grant
a diploma very much on the lines of the Diploma of Public Health
which has so largely contributed to raise the science of Public Health to
the high position it now' holds, thus conferring an inestimable benefit on
the nation.

The object, scope, and utility of a hospital in London for acute mental
diseases are admirably set forth by Dr. Maudsley himself in his valuable
introduction to this volume, and I am quite sure that it will be of in¬
estimable value to all who are interested in the progress of the science of
psychiatry, for it lays dow^n the broad principles of research and the
necessity of co-operation of certain branches of science which are requisite
for the successful investigation of such a complex subject as Mind and
its various disorders. The advice of a distinguished alienist physician

IV.

ARClin KS

of long and extensive experience whose writings and leaching on the
pathology of mind have been so lucid and luminous, and who has given
also such practical support to research, cannot fail to furtlier stimulate
the officers of the London County Asylums and all who are interested
in the pix)gi^s of our knowledge of mental diseases, and I am sure 1
am voicing the opinion of the Asylums Committee in expressing grati¬
tude for this valuable contribution to the volume; and in view of indica-
iioijs that 111 the future medical otiiccrs in the service will he more ready
to contribute scientific papers bearing upon tJie causation, treatment, and
pathology of insanity, I have considered the advisability of making an
addition to the title, and it will henceforth bear the name, “ Archives
of iNeurology and Psychiatry.'’ It is hoped and expected that a sufficient
number of papers wdll be forthcoming to keep up its annual publication.

In this volume there are two communications from distinguished
foreigners; in neither case has the work been done in the Pathological
Laboratory at Claybuiy, but there are good reasons that these valuable
papers should appear in the Archives. The paper that l)r. Ariens Kappeis,
Director of the Neurological Institute, Amsterdam, lias contnbuted on
“ The Phylogenesis of the Palseo-Cortex and Archi-Cortex compared with
the Evolution of the Visual Neo-Cortex’' was voluntarily otieied by this
distinguished neuix>logist for the reason that his researches on the evolu¬
tion of the smell area in veiiebrates coiTesj)onded with my researches
(published in the last volume) ou the evolution of the visual area in
mammals. He therefore considered the Archives a very suitable place
for this publication. Again, Dr. Giacomo Pigliini, of Reggio Emilia,
having heard of the researches which have been curried on by Dr.
Waldemar Koch and my assistant, Mr. Sydney Munii, upon “ The Chemi¬
cal Study of the Brain in Healthy and Diseased Conditions, with especial
reference to Dementia Prsecox,” oiiered a pajier on “ The Organic Meta¬
bolism in Dementia Pra^cox,” which in a measure supports some of the
conclusions arrived at from the work carried on in this laborator}\

The papers published in this volume do not represent nearly all tlie
work which has been carried on in the laboratory. Three papers have*
been read at the Royal Society and have been published in the Pro-
ceeilings, but as they had no direct bearing upon mental diseases and
a selection for this volume had to be made, it was thought better to
circulate reprints of these and of some other papers— e.g,, Dr. Schusters
valuable paper on the examination of three Chinese brains, published
in the Journal of Anatomy and Physiology, and several ix>cent communi¬
cations to the Royal Society of Medicine, in particular one by Dr.
Rondoni “ On Some Hereditary Sypliilitic Affections of the Nervous
System.”

PREFACE

V.

In conclusion, 1 wish lu tluuik my assistant, i)r. Candler, for tlio great
help which he has aftorded me in carrying out the researches on syphilis
and tuberculosis, and for the careful investigations ho has made relating
to general paralysis and its causation.

My assistant, Mr. Mann, has given me invaluable assistance in pre¬
paring this volume for the press and in the preparation of the statistics
on tuberculosis. All the microscopic preparations and photo-micrc^raphs
have been made bv mv assistant, Mr. Gearv, and to him I am indebted
f(»r liis valuable help.

FRED''’ W. MOTT.

CONTENTS.

PAftE

Introductory Pji[)er.—“A Mciitiil Hospital—Its Aims and Hses.” By Henry

Maudsley, M.D. . ... ... ... ... ... ... 1

The Pathology of Syphilis of the Nervous System in the Light of Modern

Kesearch (Morison Lectures, By F. W. Mott, M.D., F.R.S., F.R.C.P. lo

A Case of Gummatous Meningitis in a Congenital Syphilitic. By F. W. Mott.

M.D., F.R.S., F.R.C.P. . 58

A Case of Localised Syphilitic Pachymeningitis Cereijri, with Speech Affection.

By F. \V. Mott, M.D., F.R.S., F.R.C.P. . . f>:i

Tuberculosis in the London County Asylums. By F. VV. Mott, M.D., F.R.S.,

F.R.C.P. 70

Exarniiiation of the Nervous System in a Case of Chronic Lead Encephalitis.

By F. W. Mott, M.D., F.'R.S., F.R.C.P. With Clinical Notes by F. H.
Stewart, M.D. ... ... ... ... ... ... ... 117

A Case of Embolism of the Anterior Division of the Left Middle Cerebral

Artery. By F. W. Mott, M.D., F.R.S., F.R.C.P. . Idl

A Bacteriological Investigation of General Paralysis. By J. P. Candler, M.A.,

M.D. (Cantab.), D.P.H. . ". 1:18

Two Cases of Hmmorrhage into the Suprarenal Ca|)sule. By J. P. Candler, M.A.,

M.D. (Cantab.), D.P.H. . 155

The Phylogenesis of the Pala;o-Cortex and Archi-Curtex, compared with the

Evolution of the Visual Neo-Cortex. By Dr. C. U. Ariens Kappers .. J61

A Chemical Study of the Brain in Healthy and Diseased Conditions, with
especial reference to Dementia Praicox. By Wahlemar Koch and Sydney
A. Mann ... ... .. ... ... ... ... . . 171

The Organic Metabolism in Dementia Pnecox. By Dr. Giacomo Pighini ... 220

A Bacteriological Examination of the Cerel)rospinal Fluid in Dementia Pra*cox.

By G. H. Har})er Smith, B.A., B.C. ("Cantab.), M.R.C.S., L.R.C.P., and
Rae Gibson, M.B., Ch.B., M.R.C.P.E. 211

Notes and Observations on Forty Cases of New Gro>vth, including Eighteen

Intracranial Tumours. By Helen G. Stew'art, M.D. ... ... ... 217

A Description of the Brain of an Epile})tic Imbecile, showing extensive

Heterotopia of the Grey Matter. By Helen G. Ste^vart, M.D. ... 280

A Preliminary Note on Brain AVeights and Measurements in the Insane. By

Helen G. Stewart, M.D.... ... ... ... ... ... ... 207

Some Observations on a Case with Impulsive Obsessions of Suicide and Auto¬
mutilation. By H. Devine, M.B., B.S. (Loud.), M.R.C.P. ... ... 30o

A Short Account of the Incidence of Dysentery at Long Grove Asylum from its

Ojening (June 18th, 1007, to October 31st, 1008). By Geoffrey Clarke, M.D. oil

Statistics Relating to the Percentage Incidence of Intracerebral and Subdural
Hiemorrhage and Deposit in the Insane. By F. W. Mott, M.D., F.R.S.,
F.R.C.P.320

LIST OF ILLUSTRATIONS.

TAGF

Tiie Pathology of Syphilis of the Nervous System iti the Lii^ht of iModern

Keseareh. Plates I., II., 111. 1 and *J ... ... ‘J4, 25, 2d, 2S, :J2

A f’ase of (Jmnmatous Meningitis in a Congenital Syphilitic. Plate IV.

Fig. d ... .. ... ... ... ... ... ... .V.). d2

A (’ase of Localised Syphilitic Pachymeningitis Cerebri, with Speech Affection.

Figs, d an<l 5. Plate V.

...

dd.

d7, dd

'I’ulierculosis in the London (^ounty Asylums. V

lates I., IL, Ill.

lid

Examination of the Nervou.s System in a Case

of Chronic Lead

Enceplialit is.

Figs. I and 2. Plate I.

118, PJ

Id, ld(»

A Case of Embolism of the Anterior Division

of the Left Middle

Cerebral

Artery. Plate L

Idd

\ Bacteriological Investigation of General Paraly

sis. Plates L. IL,

, Ill

., IV. ...

LM

Hiemorrhage into the Suprarenal Capsule. Plate

I.

Ido

'Fhe Phylogenesis of the Palmo-Cortex and A?*ci

lii-Cort ex, com par

•ed with tlie

Evolution of the Visual Neo-Cortex. Plates

1., 11., 111., JV.

172

A Chemical Study of the Brain in Healthy and Diseased Condition.s, with

esjHjcial reference to Dementia Pra^cox. Plate I., Figs. 1 and 2 iSd. Is7

The Organic Metabolism in Dementia Pra cox. Figs. 1— d ... 2d:i, 2d!»

Notes and Observations on Forty Cases of New Growth, including Kighft‘en

Intracranial Tumours. Plates I., Jl., III., IV. ... ... 2S6, 2H7, 2S8

Description of the Brain of an Epileptic Imb<H*ile, showing extensive Hetero¬
topia of the Grey Matter, Plate.s 1., II., 111., IV., \L, VI., VH I. 2d0, 2tB.

21i2, 29d, 2\n

ARCHIVES OF NEUROLOGY AND PSYCHIATRY OF THE
PATHOLOGICAL LABORATORY

OF THE

LONDON COUNTY ASYLUMS.

“ A MENTAL HOSPITAL.—ITS AIMS AND USES.”
Hy henry maudsley, m.u.

For a great while the study of mental functions was divided between
three kinds of inquirers who, going their separate ways, never imagined
that their studies were anywise related. The metaphysical psychologist
peered into the recesses of his own mind with the zeal and sense of
superiority which have always distinguished him, and with the ).’esult for
the most part of saying the same thing over and over again, although
in sometimes different language; the physiologist pursued his patient
researches into the structure and functions of the brain and nervous
system without the least regard to the mental functions which they sub¬
serve; and the student of mental disorders, wholly concerned with them,
dreamed not of bringing the lessons of mental pathology to bear upon
the problems of normal psychology. Three classes of persons worked
diligently to elucidate the same subject without ever a word to say to each
other!

Things have changed and are steadily changing now. Although the
metaphysician still takes his lofty flights in regions of transcendental
thought, regardless of the concrete which alone gives vital meaning to
the abstract, the positive psychologist begins to take perfunctory account
of the facts of mental physiology and of the experimental results of
psycho-physical investigation. But with small profit hitherto, because,
lacking the vital appreciation of them which a thorough anatomical and
physiological training can alone give, he a])propriates partially and
superficially, without assimilating vitally, a few facts which he vitiates,
if not eviscerates, by translation into the terms of his traditional vocabu¬
lary. For the most part he fails to realise what organic life is and what

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a vital organisation signifies, and expects a successful exposition of life
in mind, and of mind in life, without a fundamental knowledge of life.
Psychology is expected to blossom as the crowning development ol biology
without the least regard to biology.

Although mind is a word in familiar use tlie usual conceptiou of it
is nowise clear and distinct, nor the use of the word constant and definite.
Wliatever it be in its essence—even if an incorporeal entity working
through corporeal organs—mind in its eveiy function implies a complex
organisation of the supreme cerebral centres, a definite mental organisa¬
tion there, which it does not precede and form, but is informed by,
depends upon, and is the function of. Such as it is now it nevc'r could
have been but for the progressive development of cer(*bral structure
through the ages of animal evolution on earth. -If the distinct conception
of an exquisitely delicate and complex organisation of finest nervous
structure in definite patterns or plexuses, intimately associated, be grasped
and held fast, it becomes easier to realise the manner of its disorg misation
when its mechanism is damaged, or falls out of gear, or wears out by
natural decay; all which effects are constantly happening in the univeisal
flux of things. Substitute the definite notion of a mental organisation
for the indefinite notion of mind when thinking and speaking of it,
and thought becomes less obscure and confused, more clear and distinct,
more positively scientific. As in truth would all thought when men
think, or think they think, were they at the pains to substitute mentally
the exact definition for the vague word.

Life being a process of conflict and communion between tln^ organism
and the external world in the endeavour to maintain a stable equilibrium
of growing being to its environment—a succession of transitoiy equili¬
briums of elements and of the whole between opposing forces—it is
obvious that when the equilibrium between a person and his circum¬
stances is so upset as to issue in a mental derangement two factors co¬
operate, namely, the innate constitutional strength of the mental organi¬
sation and the circumstances of the stress to which it is exposed. When
the internal factor is weak, circumstances do such hurt as they could not
do to a sound and strong nature, which on its part steadily and success¬
fully encounters all strains and stresses, itself strengthened structurally
by the contest and the conquest. Some well-built minds we may be sure
that all calamities rudest shocks could not confound. When the disease
befalls which is madness the infirmiiy within con.spires with the hostile
action without.

Of the two factors the internal, which is a basic inheritance from the
family stock, is the most important. Appreciating the share which
bacterial toxins and morbid ferments have in the causation of insanity,

‘‘a MEMAL HOSiMTAL its AIMS AXD L SES 'S

it is still right not to underrate the fundamental value of the individual
constitution. The delirium of typhoid fever, pneumonia, or other acute
disease is not due to the height of the bodily temj)orature; one person is
delirious with a low temperature while another with a high temperature
is not delirious; it is due to a native weakness of his mental organisation
which search into his ancestral lineage may explain. So, likewise, when
a small dose of alcohol easily intoxicates one person, or a larger dose
causes an attack of transitory mania instead of an ordinary intoxication,
the result is due to an inherited instability of mental organisation; when
it is not due, as it may be, to a brain that has been accidentally hurt
by a fracture or other injuiry to the skull rendering the person thence¬
forth extremely irritable and prone to outbursts of such passionate fury
as to be temporary madness. In its elements as in the whole organism
ro be weak is to invite and suffer hurt.

Surrounded by thousands of hostile agencies—open and secret, mighty
and minute—the organism keeps itself in health and strength by virtue
of its native strength of vital resistance, possessing which in full measure
it triumphantly defies the perilous bacterium and other dangers and
adversities of its mortal life. When therefore one mind succumbs to
hostile influences which another successfully withstands, the reaction
which it makes to its surroundings is not fitly regurated motion along
orderly lines of adaptive function but disorderly motion of disintegration.
Between the worst and the best minds there are innumerable differences
of strength to withstand and of frailty to succumb to hostile attack. A
strange theory it was, albeit supported by no less distinguished a philoso¬
pher than Locke, that all persons were born with equal mental capacities,
the differences of development being due to education. Minds, like
bodies, are born constitutionally different; and as nobody is born perfect,
everybody presumably has his weak organ, the spot of less resistance in
him, which suffers first and most when overstrained or otherwise hurt.
The misfortune is when that organ is the brain.

Gross defects or deformities of cerebral structure are visible enough
in some cases of idiocy and imbecility. Short of such gross defects,
however, there are minute and subtile defects not even microscopically
visible or yet otherwise detectable by sense, however powerful its arti¬
ficial aids. These invisible defects are presumably of two kinds, namely,
material disintegration and federal dissociation; the former a positive
deterioration or destruction of nervous elements, the latter a disunion
of organised parts which ought to act together in integrate union. When
the nervous element itself from some cause or other lacks vital force and
ensily succumbs to overstrain or toxic agencies the damage is positively
material, just as it is when motor function is enfeebled or paralysed by

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injury to motor nerve centres. When, however, tlie organisation of
federal parts which ought to act together in associated function is
impaired the result is dissociated and almost independent action, not
otherwise than as when associated movements are dissociated in spasms
or convulsions. In the performance of ideas as in the performance of
movements ataxic disorder sometimes occurs, a mental not unlike a motor
ataxia.

Accordingly the varieties of insanity fall naturally into two
principal classes. Wlien the material element is damaged either by
direct injury or by toxins introduced into the body, or engendered in it
by some mishap in the processes of metabolism, its disordered energies
are displayed in the utter incoherencies of delirium and acute delirious
mania. Remembering in what furious fashion the virulent bacilli of
tetanus and hydrophobia act perniciously on the parts of the nervous
system which select them or they select, and thereupon imagining a
toxin to select and affect the supreme cerebral centres with a like virulent
energy, it is not difficult to conceive the production of an acute delirious
insanity. There is then no system or method in the madness, no organisa¬
tion of disorder, at any rate during the acute stage, albeit more or less
colierent organisations of disorder take place when things become chronic.
Could we dive into the turbid recesses of the acutely melancholic mind
and realise what goes on there we should discover a condition of things
in which the formal apprehensions of outward impressions are dissolved
and they grossly misinterpreted in consequence; sights, sounds, touch, and
odour being translated into threats, signs, omens of hurt. It is strange
to see how completely the sufferer then misinterprets innocent words and
gestures, seeing in them hidden symbols of danger, mistakes the identities
of familiar persons about him, fights against tendered help as if it were
a deadly assault. His relations are not with the external world of
realities, they are with the illusions into which these are translated by
his disordered mental activities. Like as every sane person does sanelv,
so he creates his own external world, a world of turbulent turmoil, in¬
sanely. Low vitality of nerve element is naturally and necessarily
accompanied by low spirits; its gravely menaced life, then unable to
receive and react fitly, reacts convulsively at random.

In the other class of cases the forma of thought are not entirely
disintegrated; the disorder showing itself rather in a dissociation of the

federal tracts or centres and in the steady organisation of disorder_in an

organised insanity. For instance, the victim of a mania of persecution,
rational in other respects, believes himself to be subject to all sorts of
impossible persecutions in all sorts of impossible ways, and cannot be
brought to doubt the evidence of his own consciousness by the concurrent

A MKNTAL ITOSTMTAL- ITS AIMS AND I SKST)

and consistent testimony of all those wlio come in contact with him. In
the further devolopment of his mental disorder, vexed and perplexed to
account for so strange and persistent a hostility, which he has nowise
deserved, he grows into the settled conviction that he is not the person
he has hitherto been thought and thought himself to be, but really a
person of distinguished, perhai)s royal, parentage kept out of his natural
rights by a secret conspiracy. Such an amazing system of a so powerfully
organised and all-pervading a persecution must have an extraordinary
meaning. Given the truth of his premises what other or otherlike con¬
clusion could reason come to^ When all is said, reason is always an
inevitable machine-like deduction from the premises, which can never be
exactly the same in different persons, and at best for a finite being in
an infinite universe must necessarily always be incomplete and arbitrary.
Take, again, the victim of a jealous and unreasonable suspicion of his wife’s
secret infidelity who, constantly on the watch indoors and out-of-doors,
through windows and keyholes, to discover proofs of her unchaste mis¬
deeds, finds it in the most trivial and perfectly innocent circumstances,
translating them into the terms of his dominant mood. He, too, a rational
man for the most part in all other respects, all the while perhaps doing
fairly his daily work in his business. Side by side in his mind, if not in
amity at any rate without open hostility, dwell sound reason and utter
unreason; the insane delusion apparently no alien but quite at home
there. As in truth it well may be seeing that it is then probably ingraft
in the stock and marks an insane inheritance.

In such cases, the normal unions of federal tracts being disjointed, a
pathological organisation of disordered activity takes effect. Thus it is
that a class of organised insanities differ in symptoms, pathology and
mode of causation from the insanities of positive nervous deterioration.
In them the question is not so much a question of material injury to
nerve element as of morbid growth—of the steady development of a mor¬
bid character from the root of a bad constitutional inheritance : an extreme
instance indeed of the bad mental growth by which narrow and fixed
prejudice blinds the ill-constructed mind to truth, be it never so plain.
Nursed passion or prejudice ripens into bad habit of thinking and feeling,
and bad habit grows into organised disorder. As in dreams temporarily,
so in insanities, organisation of disorder is a constant and natural process.
Part of the work in a well-organised mental hospital might not unfitly
be a systematic instruction in mental lij’^giene in its wddest sense; instruc¬
tion based positively on demonstration by actual examples of the natural
and necessary effects of bad habits of thought and feeling.

As there are two different classes of insanity so there are two different
orders of inquiry: First, a pathological inquiry is concerned with the

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minute inveatigaiion ot liie pliysical and chemical causes of the derange¬
ment and with the morbid changes ot structure; for which purpose a
well-equipped pathological laboratory in the hospital is indispensable.
Secondly, a more general inquiry ought to be made into the individual
character, the hereditary inhuences which have wrought in its constitu¬
tion, the sort of education which it has undergone, and the circumstances
of life which have att'ected its development. These ehects are more or less
legible in the mental complexion of everybody had we only the insight
to discern them; for as the various features of a countenance are woven
together in its whole complexion or physiognomy, so the moods of feeling
and habits of thought are represented in the individual’s mental com¬
plexion and declare his character. However that be, the problems of a
positive scientific study concern the material constituting the mental
fabric and the physico-chemical causes of hurt to it, on the one hand;
and, on the other hand, the character of the fabric and its edification.

The latter inquiry is not only a legitimate part of a scientific study
of mental pathology, it has also important practical bearings. Obviously
it is not sufficient to consider the organism only as a physiological
machine liable to be deranged by subtile toxic matters; it is incumbent
to study the individual also as a social being. Mental organisation being
effected by progressive adaptation to the social as well as the physical
environment, tradition, custom and convention constitute a social
medium which is ingraft in the individual’s nature and to which he must
conform outwardly if he is to live and function as a social unit in it.
Broadly speaking, insanity is such derangement of mind as prevents its
victim from discharging his normal functions in the social body of w hich
he is a member; therefore the nature of the social medium and his
relations to it must ahvays be well considered in a true exposition of its
causation and character. The feelings, thought and conduct befitting one
society or even one station of life in the same society are notoriously
quite unsuitable to a different society or to another station in life; so
alien from it indeed as to alienate the individual and thus to be a mental
alienation. Were a Prime Minister or an Archbishop to do openly in
the public street what a savage does indifferently among his huts, or to
go about town in his shirt sleeves with a short pipe in his mouth, he
would be pretty sure to be counted a person of unsound mind and a proper
person to be put under care and treatment. Or were anybody, like an
inspired ^fahdi, to go about the city proclaiming the immediate end
of the world and urging everybody to go down on his knees in instant
prayer he would no doubt be sent to a lunatic asylum. So essentially
does the special social medium enter into the constitution of the individual
mental structure, and so necessary is it fo take strict account of the

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"a mental hospital—ITS AIMS AND I'SES

character of both and their relations in deciding what is and what is not
insanity; and that especially when it is a serious question of medical
certificates and legal restraint.

Alike in the interests of medical men who certify and are liable to
an action at law for what they do, and of those who are liable to be
certified and may afterwards be socially prejudiced thereby, it is evidently
most desirable that medical students should be taught carefully what is
a good and sufficient certificate of insanity, what cei'tificJ'ation involves,
and in what cases it is justified. At present it would hardly be an
exaggeration to say that more than half the certificates signed are sent
back by the superintendents of asylums for correction or amendment. A
well-staffed mental hospital will supply effective means of clinical in¬
struction to students tilting them for their work when they go into
medical practice; it will also supply a succession of trained medical men,
interested in the special study and imbued with a scientific spirit, avail¬
able to take office in the county asylums.

Many interesting and important questions, it is needless to say, still
await the satisfactory answers which systematic study of insanity in a well-
organised mental hospital may be expected to give in due time. What is
the quality of the family stock, and what are the natural developments
of it, good or bad, under similar and under different conditions of life?
It is not sufficient to inquire whether a parent or other near relative was
insane, it is necessary to trace out the fortunes of other members of the
family who were or were not insane—how they lived and how they died.
How is it that, as sometimes happens, one child of the same family
becomes insane or commits suicide, another grows to high intellectual
eminence, and the third is a hopeless castaw^ay or actual criminal?
Certain it is that a congenital moral imbecile, endowed the while perhaps
with a singularly acute cunning, yet destitute of the very elements of
moral feeling, will be usually found to own an insane inheritance. In
what ways, if at all, do the thoughts, feelings and doings of one genera¬
tion affect the natures of succeeding generations? Is it so certain, as
nowadays so confidently assumed, that acquired characters of mind and
body are never inherited? What are the periods of physiological
d;^velopment and decline most dangerous to a weak or unstable nature,
what the varieties of insanities most likely then to occur, and what the
measures—intellectual, moral and physical—best suited to counteract the
danger in a particular case ? Here, as elsewhere, an individual psycho¬
logy is the special want. What diseases in the parents other than
insanities are most liable in breeding to conduce to mental derangement
in the offspring? The effects of inter-breeding of different disease-
tendencies is a subject which yet calls for and may be expected to repay

ARCIIIVKS

systematic study. Wlien the intellectual and moral nature oi the indi-
v^idual is viewed as a natural process of organic development, the inevit¬
able product of the nature within and the nature without him, the
absolute and artificial division between the physical and moral must
needs disappear and the essential unity of mind and body be reflected in
one fruitful mental science.

Eecognising the unity of body and mind, and viewing mind in its
mortal manifes'tations as the supreme and, so to speak, subliminated
expression of vital function, it plainly appears* that the study of its
unsound manifestations can only become fruitful by means of a thorough
a.nd complete observation of all the bodily functions and of all their
manifold disorders. Old writers, not without a dim notion of this unity
of organic being, set forth the special effects which they supposed the
several internal organs to exeii upon the moods of mind, enumerating
tlie various so-called morbid humours engendered by them; insomuch
that each organ was believed to have its special animal spirit. Which,
iif ter all, perhaps, it has in some sort seeing that, besides its specific bio¬
chemical function, it may exert its specific organic rhythm. It is
certainly not inconceivable that a special organ, thrilling with infinitely
subtile motions through every element of it, does radiate fine rhythmical
tlirills to other special organs in intimate vital sympathy with it. Black
bilt? was the supposed cause of melancholy, as a liver out of order is still
the cause of a gloomy depression of spirits. Thus the passions were
located in different viscera: courage in the liver, a coward being wdiite-
livered, spleen in the spleen, compassion in the bowels, good or bad
feeling in the heart. Translate the crude notions into the more positive
but still largely conjectural notions of the present day, and they point
to the subtile matters of the so-called internal secretions which, directly
or indirecfly, act upon the brain; not only physiologically in the consti¬
tution of the emotions when functions are sound but also pathologically
when things go wrong. Courage may not reside in the liver, but when
tlie liver is disordered its representation in the brain where the emotion is
kindled and felt answers to the local disturbance; the liver may not have
its special animal spirit, but it has its special effect on the animal spirits;
may not engender its owm “ morbid humour,” but certainly engenders
matters which morbidly affect the mood or humour of mind. These old
writers, after all, conceived the general notion of an organism in whicli
all members are members of one body and members one of another; a
notion which is apt to be lost sight of nowadays when special physical
and chemical researches are pursued witli such diligent minuteness and
almost expected to explain its mysteries.

Indispensable, however, these minute researches certainly are, and

A MENTAL HOSPITAL—ITS AIMS AND USES

9

»>

indispensable the means and appliances of suitable laboratories to carry
them out. Into every mental act bodily functions enter, and every
bodily function is affected mentally. Exalt the glory and grandeur of
mind as we may, the rude fact remains that it is not always either grand
or glorious and that its tenure at best is precarious; a defective thyroid
notably weakening and almost extinguishing it, and a poison generated
by a mishap to one or another of the subtile metabolic processes inflaming
it into a delirious mania or precipitating it into a profound melancholia.
A complete clinical and pathological study of insanity cannot therefore
be made without an adequate knowledge of all the diseases treated in
general hospitals and of the morbid effects discovered in their patho¬
logical laboratories. That indeed is strong reason why a mental hospital
should be near to and in close and constant touch with the medical
work and thought of the general hospitals. These on their part might
profit by the close intercourse, being incited thereby to study the special
mental features of the different bodily diseases, a study hitherto for the
most part neglected. Has not every bodily disease perchance its special
mental complexionUnquestionably the distribution of diseases, mental
and bodily, into separate tight compartments and the corresponding
isolation of minds limited to the study of them contradict the very
principle of the unity of body and mind and are fraught with the worst
hindrances to the progress of medical science.

Although the clinical study and exposition of mental disorders lias
always been diligently and profitably pursued, much yet remains to be
done. A small hospital filled with a constant succession of patients would
evidently afford opportunities of such particular attention to individual
cases as cannot well be given in a large asylum crowded with persons in
all stages of mental disease for mere detention. Isot only because more
close and exact oliservations might be made, but also because the attend¬
ance of many persons, physicians and students, stimulating one another
by constant intercourse, occupied at the same time with the study of
diseases in the general hospitals, would sharpen observation, suggest
inquiries, keep fresh the interest, prevent routine of thought, feeling
and treatment. The insane patient also could hardly fail to benefit by
the surrounding atmosphere of sanity.

Hitherto, perhaps, the tendency has been to make too much of a
group of symptoms, putting it into a sort of tight compartment and
labelling it with a special name, as though it represented a definite
disease; after which it is talked of sometimes as “ a clinical entity ” or “ a
pathological entity.” As if such metaphysical terms were not pure
nonsense or had more than descriptive meaning! Nature, everywhere
continuous, nowhere divided into quite separate compartments, has no use

10

AHCIIIVKS

for entities. Such habit tends to hinder a luiger and truer view of
insanity as a disorganisation of the the mental organisation varying in
degree, place and character. Delirium, delirious mania, and acute
mania represent different degrees of dissolution of mental forms connected
by intermediate states, not really different diseases. In like manner
mania and melancholia, although properly divided into classes for
descriptive and other purposes, are not separated by distinct lines of
division in nature, but merge into one another by gradations; cases
frequently occurring which might with equal justice be described as
examples of one or the other class. The same person shall pass from
one end of the scale of mental disorder to the other. Indeed, the natural
course of things is, perhaps, first, melancholic dejection and irritability,
then the quasi-convulsive reaction of mania, and finally the devastation
of dementia. As the mental organisation, when whole and sound, is a
confederation of federal parts, the diversities of its disorganisations
naturally present different features according to the place and character
of the disorganisation and the consequent symptoms. And as minds,
like bodies, differ naturally in structure and development, no two minds
nor bodies being exactly alike, it would be strange if they did not differ
accordingly when their functions are deranged. Melancholic and pessi¬
mistic moods are as natural for the most part in everybody's life as
exalted and optimistic moods, and in their extreme degrees mark the
opposite moods of different temperaments. No marvel, then, that mania
and melancholia sometimes alternate periodically in the unsound mind.
Insanity invents no new qualities of mind; it only exaggerates or
distorts the natural qualities.

Another want notable in the clinical study of insanity, besides the
regular study of the individual character in the particular case and the
special causes of its breakdown into the particular mental derangement,
is the special conditions under which one form of disorder passes into
another form. How is it that one mind falls into a deep melancholia
and stays there while another, perhaps without previous apparent depres¬
sion, flares into mania P What are the exact conditions of things under
which melancholia passes into mania in the same person, and conversely
of mania into melancholia? How is it that these apparently opposite
forms of mental disorder alternate in the same person with tlie frequency
and periodical regularity which they show in so-called folie circulairc?
And go on alternating then during a long life without so inuch as any ap¬
preciable damage to the mind ? What are the varieties of insanity which
distinctly denote an insane inheritance? And what the special forms of
insanity that are the results of special varieties of unsound ancestry?
What, again, the special causes, constitutional and pathological, of the

“ A MENTAI^ HOSEiXAL—ITS AIMS AND USES ’

11

extraordinary mental elation and grotesquely grand delusions which
characterise general paralysis of the insane? These and other easily
imaginable questions still await the solutions which they may be
expected in due time to receive through patient and systematic study
under favourable conditions in a well-stalfed and well-equipped hospital.

On the purely practical side it is hardly possible to overrate the good
which may be done by individual treatment applied particularly to the
susceptibilities of the individual character. To every physician con¬
cerned with the insane it must have happened, listening to the sad story
of one who had been discharged recovered from a large asylum, to hear a
relation of the despairing feelings in the depressing surroundings and
under the dreary and monotonous routine of the life there, and the
expression, perhaps, of a firm conviction that but for the sympathetic
attention and encouragement of a particular nurse or attendant he or she
never could have recovered. Again, it notably happens sometimes that a
turbulent and aggressive maniac, angrily resenting and violently rebel¬
ling against the rude mechanical control of several attendants, yields
submission to the quiet tact, patient attention and discreetly sympathetic
management of a particular attendant. So much may be done in an
asylum, as out of it, by humouring the susceptibilities of the individual.
If such tact be necessary in the converse of daily life, as it certainly is—
in the family, in the school, with children, with servants, with men and
women in all the relations of social life—how much more proper is it in
dealing with the exasperated sensibilities of an insane person who has
lost his power of seif control, is possessed perhaps with suspicions or
exalted delusions, and finds himself in a situation of restraint which is
utterly unintelligible to him and against which his natural instinct
struggles blindly? Or with the despairing melancholic who, believing
himself irremediably disgraced in this world or doomed to eternal
damnation in a world to come, finds in the cheering tone and apt word
of encouragement a gleam of hope partially dispelling the gloom and
promising a brighter future. Little confidence would the medical prac¬
titioner in attendance on ordinary bodily disease inspire, and small good
would he do, who had not the sense and tact to humour the susceptibilities
of his anxious and often querulous patient.

A complaint often bitterly made by persons who have been dis¬
charged recovered from asylums is of the coarseness, roughness and in¬
difference of attendants, and of the degrading humiliation of being
ordered about by them in daily routine like so many sheep, without the
least regard to personal feeling. Such system of routine is no doubt more
or less unavoidable in a large asylum crowded with patients in all stages
of disease, but it is none the less apt to be accompanied by an utter want

12

ARCHIVES

of the sympathetic imagination which might realise what the particular
patient, not deadened into stolid indifference to his surroundings, may
feel. A small hospital might therefore serve also as an excellent training
ground for nurses and attendants, who could afterwards go into tlie
service of the large asylums, not only fitted by their training for the
bodily care of their patients but imbued with a sense of responsibility
to them as mental beings.

Another probable advantage of the close observation day by day of the
individual patient would be a perception by physicians and nurses of the
favourable psychological moment when at the dawn of convalescence the
opportune removal from the asylum to a convalescent institution or to
private care might save the tottering reason of the patient who, theu
awakening to the painful consciousness of his sad surroundings and
realising the seeming hopelessness of the situation, might otherwise sink
into despair, abandon hope, and gravitate into dementia.

That there are crowds of incurable cases of insanity congregated in
large asylums is undoubtedly owing in some measure to the common
neglect of early treatment w hen the malady is most curable. The longer
the disease has lasted the smaller are the chances of recovery; and the
time soon comes in some cases w’hen, if neglected, there is no remedy,
llere, as everywhere, the right treatment is to stop the beginnings of
mischief. It may reasonably be expected, therefore, that besides the
prevention of incipient insanity by wise counsel and treatment in its
out-patients’ department, the early treatment of acute insanity in a
special hospital will prevent the present necessity and perhaps lasting
expense of placing some patients in a lunatic asylum—the very name of
which is perhaps a terror, the remembrance a sort of nightmare, and the
social consequences a life-long prejudice.

The recent outburst of indignant jjiotest by the neighbours of a
large asylum against the permission of an occasional walk outside its
grounds to harmless patients was not needed to prove how generally
tlie person afflicted with mental disease is looked on as a sort of social
castaway and how prejudicial a stigma rests on one who lias been con¬
fined in a lunatic asylupi. Exaggerated apprehensions of danger
and the common notion of insanity as a disgrace to be concealed or
put out of sight, rather than a disease to be soon and wisely dealt
with, are still responsible for much neglect of early attention and
for many impediments in the way of its proper care and treatment.
If a mental hospital in close touch with the general hospitals and medical
schools helps to instil the notion of disease and to dispel unwarranted
prejudices it will not have been built in vain.

13

MORISON LECTURES.

Jiv F. W. MOTT, M.D., F.R.S., F.R.C.l*..

I)ii‘ector uf the Patliulo^iital Luixiratory, London County Asylums; Physieian to

Charing Cross Hospital.

Delivered at the Royal College of Physicians, Edinburgh,

January ‘2oth, 27th and 29th, 1909.

PATHOLOGY OF SYPHILIS OF THE NERVOUS SYSTEM
IN THE LIGHT OF MODERN RESEARCH.

^Ir. President and Fellows of the College: Allow me to thunk you for
the great honour of having been invited to give the Morison Lectures in
tlus ancient College of a city, so long renowned as a great seat of medical
science and learning.

In considering the general pathology of syphilis of the nervous system
it is not necessary to refer to the different bacterial and other organisms
which have been described by various authorities as being the specific
agent in the production of the lesions characteristic of this disease before
the discovery of the Sinrochceta Pallida by Schaudinn. This organism,
wliether it be, as its discoverer believed, a protozoon or a bacterium or
micro-organism between a protozoon and a bacterium, is regarded as the
specific organism of syphilis by those best competent to judge, viz.,
Metchnikotf, Hoffmann, Neisser, Levaditi, Bertarelli, Shennan, and many
others. Metchnikoff and Roux were the first to demonstrate experiment¬
ally the communicability of syphilis to animals and to show that the
nearer the animal approached to man, the more the disease approached
in its characters and virulence the human form of the malady. Thus,
although other animals, especially apes and anthropoid apes, have been
successfully inoculated, the chimpanzee alone reproduces with absolute
certainty the human symptomatology. This is as we should expect, for
the blood precipitin reaction of this anthropoid approaches most nearly
that of man. The experiments of Neisser, Hoffmann, Bertarelli, Levaditi,

14

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and numbers of others liuve confirmed this important discovery, and
many new facts have been added to our knoAvIedge of the general patho-
logy of syphilis by experiments on apes and other animals, and 1 would
mention in particular the important discovery by Bertarelli, who was
able to inoculate the spirochaete into tlie cornea of the rabbit and
transmit it through a series of such animals. Levadlti has experimented
successfully with the cornea from one of these animals and not only
transmitted it through a series of rabbits, but used the cornea infected
with spirochaetes to produce an infection of the eyelid of an anthropoiil
ape. Lastly may be mentioned the important observatioiis upon the bio¬
chemical changes in the fluids of the body by the Wassermann, Neisser
Brilck method of serum diagnosis. Upon this tripod, of the discovery
of the specific spirochaete, the communication of the disease to apes and
the serum diagnosis, a vast amount of most valuable work rests, the tripod
is mutually supporting and every day fresh evidence is forthcoming to
strengthen the opinion that the true cause of syphilis has been dis¬
covered; that, although as yet no vaccine has been successful, this is
no longer a hopeless outlook; and, lastly, a most valuable means of
diagnosis of syphilis and parasyphilis has been obtained.

The MicuoniOLouv oe SiriiiLis.

The Spirochata Fallida examined in fresh preparations is seen with
much greater difliculty than other coarser spirochaetes which may exist
in the primary sores on the genitals or secondary papules of mucous sur¬
faces. Hoffmann states in order to find them, it is necessary to seek the
edges of red blood corpuscles, to which they often are seen to be attached
by one end (a process of chemotropism). It is barely thick and
possesses on an average 8-12 very regular, narrow, and very steep coils,
the height of which at the ends diminishes somewhat. [Vidt Figs. 1, 2, 3,
4, Plate I.) The length of this cork-screw-like organism varies within
wide limits, from a few up to 26 coils or even more. Examined with a
paraboloidal reflecting substage condenser, by which living organisms
appear light on a dark background, the Spirochceta Pallida can be seen
to rotate on its long axis and oscillate to and fro with a pendulum-like
movement, contrasting thus with the coarser and larger spirochaetes,
which have an eel-like movement. An observation of Hoffmann showed
that the untreated serum of a syphilitic patient caused a cessation of
movement after about a couple of hours.

SYPHILIS OF THE NERVOUS SYSTEM

15

DIFFERENCE BETWEEN THE SYPHILIS SPIROCHAETE AND OTHER KINDS
OF SPIROCHA ETES.—(///i/fwm/i/O.

Syphilis Spirochaete.

1. —Large size 10-16 /u on the average, still

often more than this. The extreme
tenuity of the fibre {\ ^). This relation
between length of fibre and its thickne.=s
is very characteristic.

2. —Very slightly retractile in fresh pnipara-

tiuns, therefore only visible with the
Vjest apuchroinatic lenses.

3. —Ends are pejinted, often terminating in

long red threiids.

4. —Movements screw-like around this long

axis ; lateral pendulum movements ;
movements forwards and backwards
still less active, often remains a long
time inactive anchored to a blood
corpuscle, whilst it exhibits rotatory and
slight pendulum movements.

5. —The spiral posst'sses deep, steep, and ver}^

regular coils of cork-screw f<»rm. Fil)res
excessively thin in comparison to tlie
length and depth of the spiral.

fi.—Relation of tlie depth to the letjgth of
the coils mostly gn'atei* than 1, namely,
1-0—1-2; VO—i-ry.

7. —(Jreat elasticity and retention of the

spiral form, therefore with more difficulty
deformable.

8. —Only trifling variations in breadth in

respect to the form ; only the length
therefore, also the number of coils
variable.

9. —It is coloured by Gii'insa red (general

scattered chromidial siibstauec).

Other Forms,

1. —Fibres relative to their length far

thicker, therefore they have a plumper
appearance ; the finer forms are mostly
shorter than the sp. pallida.

2. —Strongly retractile, and therefore easily

seen in fresh preparations.

3.—Ends blunt. End tlireads seldom seen.

4.—Lateral movement much more active,
eel like and sinuous, and more rapifl
change of position. Anchors to cells
much less frequently, and detaches
itself quicker.

T).—Coils Hatter, irregular, in many forms
(Sj). Drtitimn) narrower fibres, thick and
plump in comparison to the breadth of
the coils.

6.—The known relation is smaller than 1.

7.—Softer and more pliable, therefore the
form is more changeable.

s.—Great variability, all transitions from
small to large, from thick to thin
examples.

9.—Colour more bluish red ; nuclear rod or
rod nucleolus in plasma often demon¬
strable.

Scliaudiiiii and Hoii'manii were able to prove that the S/nrochtvta Pallida
is found in all cases of syphilis and is never found in any other affections.
Thej" also discovered spirochaetes in fresh preparations not only on the
surface of the chancres and papules, whether of the skin or mucous
nienibranes, hut also in the depths of the tissues and in the juice of
enlarged inguinal glands of syphilitic cases. Metchnikoff, fi,oux, and
Levaditi have demonstrated the presence of the spirochaetes in chancres
on the face and penis of monkeys in association with other organisms;
they also found the spirochaete in papules. Buschke and Fischer dis¬
covered spirochaetes in abundance in the liver and spleen of an infant
affected with congenital syphilis, and Levaditi demonstrated numbers of

16

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spirochaetes in the fluid contained in the bullm of pemphigus occurring in
a congenital syphilitic infant. Since then an ever increasing army of
workers have, with a few notable exceptions (Saling Schulze), sup¬
ported the discovery of Schaudinn. In fact, this organism has been
shown in every possible lesion which is definitely syphilitic. In some
cases they cannot be found in the primary sore unless a very careful
search is made, and even then the search may not be successful. The
same applies, with even more force, to the secondary eruptions.

The spirochaetes have been discovered in the capillaries of the skin
and in the perivascular tissue. Although only occasionally found in
the blood, the spirochaetes are more numerous in the lymph and
lymphatic organs in general, and, according to Metchnikoff, their
presence in lymphatic vessels may be said to be constant in syphilis, and
it is at times possible to see a very large number in the perivascular
spaces, although their number in the corresponding blood vessels may
be exceedingly limited. I have examined a number of primary sores,
mucous tubercles, and cutaneous papules sent to me from the Lock
Hospital and in all cases smears have shown spirochaetes by the Giemsa
method,* sometimes, however, only after long and diligent research. Iii
one case of secondary papules I found the spirochaetes by Levaditi
method,t although I was unable to find them in the blood {vide Fig 7,
Plate I.). When the disease becomes generalised and there is a polyaden¬
itis, the organism can be found in glands fai' removed from the primary
lesions; thus Lewandowsky found spirochaetes in the juice of the epitro-
chlear gland. It is presumed that for a short time, perhaps some hours,
the organisms remain in the lymph clefts and spaces of the tissues at the
point of inoculation; there it multiplies, and in a short time extends
into the lymphatics and produces microscopic changes, although
microscopic changes are not visible. In confirmation of this it may be
mentioned that Levaditi and Yamanouchi have inoculated the chimpanzee
with syphilis, and at a time when the point inoculated did not show the
slightest microscopic indication of primary syphiloma they were able to

♦ Giewm Method, —a film by expression and expose immediately to osmic acid
vapour for two minutes. Dry in the air; then place in solution containing one drop Giemsa
stain to 1 cc. distilled water for several hours. Wash in water and decolourize in solution of
5 per cent, tannin for some minutes. Wash again in'water, and finally in absolute alcohol.

t Levaditi Method .—The tissues are fixed in 10 per cent. Formol for 24 hours or longer, and
then left overnight in 95 per cent, alcohol, after which they are placed in distilled water until
the pieces sink. They are then placecl in 1-5 per cent, solution AgNOj 90 cc.. Pyridin 10 cc.,
for 2 to 3 hours at room temperature, and 3 tn 6 hours in a dark oven at 45 ° to 50*^ C. The
tissues arc then directly transferred to a solution containing 85 cc. (4 per cent. Pyrogallic acid
solution. 90 ec., acetone 10 cc.) and 15 cc. pvridin, in which they remain overnight. They
are then washed in distilled water, hardened in increasing strengths of alcohol, embedded
in paraffin and sections 5 ^ to 10 /a in thickness cut. These are stained by Polychrome
methylene blue and differentiated with dilute elveerine. ether mixture, or tannic acid solution.
Other authors use 1 per cent. Toluidin blue or Iodine green.

SYPHILIS OF THE NERVOIS SYSTEM

17

(lotect an active pullulation of spirocliaetes and specific histological
changes. The same investigators have recently published some very
interesting researches upon incubation in syphilis. Tliese observers have
conducted a series of observations on keratitis in the rabbit inducTd by
introducing a small portion of an infected cornea into the anterior
chamber of the eye and by killing the animals at varying periculs of time
afterwards. They have also introduced the infected cornea of the rabbit
beneatli the skin of the eyelid in apes and a chimpanzee, and examined
the tissues of spirochaetes by the Levaditi method. They have formulated
the following conclusions. The period of inoculation which precedes the
manifestation of the primary syphiloma of the monkey and the specific
keratitis of the rabbit is not due to the existence of an evolutional cycle
of the * Treponema pallidum. It corresponds to the slow but progressive
histological lesions provoked by tlie pullulation of the microbe of syphilis.
This pullulation is not marked at first, in consequence of a defective
assimilation caused, on the one hand, by a change of medium, and, on
the other, by the conditions which preside over the supply of nutritive
materials. But, as soon as the vessels and new-formed cellular elements
assure to the treponemes the nutritive principles of which it has need,
the multiplication by the parasite becomes active, and j)uts an end to th(‘
period of incubation.

The organisms after local development at the point of inoculation
in man and in the anthropoid ape soon reach the nearest lyni-
})hatic glands, where probably they again multiply in the lym])h
sinuses and spaces, setting up an adenitis; these changes may be bio¬
logical, provoked by the organism for its perpetuation, and not, as
taught, in the nature of a defence on the part of the tissues against the
invasion by the organism. The living organism usually prevails and
passes into the general lymph stream, causing polyadenitis ami an
infection of glands remote from the seat of inoculation. The organisms
may thus find their way into the thoracic duct, and a general infection
of the blood stream takes place, with the development of the secondary
eruption (roseola). Moreover, a profound biochemical change occurs in
Ihe blood and fluids of the body {vide p. dO). Occashmally, as hrsi
pointed out by Lang, and as I myself have observed in several cases
quite early in the disease, even before the primary sore is healed,
sym])toms pointing to meningitis may occur; also, as will be point(*d
out later, and which I have seen illustrated by many examples, the most
severe and the most intractable cases of brain and spinal sy])hilis occur
within the first twelve months after infection; it is quite probable that

* Somi* Miithurs pii'fer tliis name to Spi rochuto Pall'ulti.

AKClllVKS

IS

the meiiiiigeh were infected at the time of the roseolar rash in some of
these cases, but the symptoms occurring then were slight and overlooked.
Mot infrequently severe symptoms of meningitis have occurred within a
few months of tlie primary sore. It is reasonable to suppose that it the
spirochaeie is the cause of the secondary cutaneous eruption by a sort
of metastatic process in the skin capillaries, that the same may occur
in the meninges. The following case reported by Gautier and Maloizel is
interesting in this respect, and tends to support that conclusion. A
young woman affected with secondary sypliilis had seven successive
attacks of cutaneous eruption, simultaneously with sudden fever, head¬
ache, stiffness of the neck, and vomiting, accompanied by lymphocytosis
of the cerebrospinal fluid; a complex of symptoms of syphilitic
meningitis. Again, Boidin and Weil have reported a most interesting
case of a young man, aged 18, who had (1) a hard chancre in the middle
of June; (2) headache the middle of duly; .symptoms of meningitis and
lymphocytosis of cerebrospinal fluid August 5th; roseolar rash August
12th. Cure of the meningitis by inunction August 17th. (See also a case
of mine, page 87.) It is a pity that some of the fluid of such cases was
not used for experimental inoculation of an ape. So far only Hoffmann
has succeeded in show ing that the cerebro.spinal fluid may be infective, for
he has successfully inoculated a monkey with the cerebrospinal fluid
obtained blood free and taken with all precautions from a man suffer¬
ing with a papular syphilide. Meisser States that Dohio and Tanaka
iiave found spirochaetes in the cerebrospinal fluid in the case of a
patient with a papular eruption; a second examination, as well as one
by Meisser himself, was unsuccessful. It may be that (•entrifuging a
fluid of such low^ density w’ould disintegrate stich delicate organisms.
Again, we know* that it is not infrequently impossible, except by culture
or inoculation, to find tubercle bacilli in the cerebrospinal fluid of tuber¬
cular meningitis. Until experimental investigations have been made
willi fluid obtained from early acute cases of syphilitic meningitis, the
absenc(5 of the organisms upon microscopic examination and failure
of experimental inoculation is no valid argument against their being the
cause of the meningitis. It may be said that if the spirochaetes are the
cause of the meningitis, they could be shown in sections or in tilms of
the (‘xudation. It is seldom that sy])hilitic meningitis is rapidly fatal,
and cases would rarely come under early enough observation; moreover,
not more than 1 or 2 per cent, of syphilised persons suffer with ohfntsivr
symptoms of meningitis, and they seldom die in conse(|uenc(‘ then^of,
and still more rarely do they die for at least some months after the onset
of symptoms. I have been unable by the silver or Giemsa method to
find spirochaetes in the exudation of ty])Ical cases of syphilitic meniiig-

SYPHILIS OF TllF XERVOLS SYSTEM

itis. liut I was unable to find trypanosomes in the similar cell inhltra-
lions oi the meninges and perivascular spaces of sleeping sickness
although I have examined quite a thousand sections obtained from thirty
cases. Yet, it cannot be doubted that the T'rypanosoma Gamhiense is
the exciting cause of the meningo-encejihalitis.

Syphilis is characterised by being an eruptive malady following
the inoculation of the virus, presumably the spirochaete of Schaudinn,
and by the possibility during the remainder of the life of the individual
of fresh eruptions occurring in connection with the existence of the virus
in the body. A blow may be followed by a gumma, or a syphiloma may
occur spontaneously in any part of the body at any period of time after
infection. Microscopic examination shows that essentially the same
tissue reactions occur in these late manifestations of syphilis as in the
primary or secondary stages. It is well known that tertiary lesions are,
as a rule, non-infective; consequently, we should not expect to Knd the
active agent, or what we believe to be the active - Sijirochwta

Pallida —except in a few instances, and then only in small numbers.
This is actually what lias occurred. For a long time attempts to prove
the existence of the spirochaetes in teidiary lesions failed, and this led
to the not unwarrantable view (whicli may be true) that the organism
may exist in a latent and attenuated, possibly intracellular form, and
it is possible that late manifestations may be the result in some cases of
secondary lesions which have remained latent uuiil raised into activity
by some exciting factor, such as exposure to cold, trauma, and toxiemia
—microbial or otherwise; for» at no period after infection may
such syphilitic meningitis occur. On p. 58 I have described a case of
congenital syphilis in which cerebix>spinal meningitis occurred in a girl
of IG. I was unable, however, to find spirochaetes, although tin*
meningitis was very active and typically syphilitic in its histological
character. It must be admitted that this is a part of the microbiology
which, is unsatisfactory. The spirochaete, however, has, in a few in-
slaiices, been found in a gummatous tumour. Schaudinn found it in a
gumma of the liver. Blaschko recently claims to have discovered spiro¬
chaetes in scrotal pajniles whiidi occurred sixteen years after infection.
Bcuter and Schmorl claim to have found spirochaetes in syphilitic aort¬
itis embedded in the proliferated intima between the fibrils, sometimes
in places in which regressive changes are absent. Moreover, Benda
claims to have demonstrated typical spiral, straight and granular forms
of the spirochaetes in the external layer of the media, and still more
in the connective tissue adjacent io a patch of .syphilitic endarteritis,
•lust as there are, relatively, but few successful observations jmiving the
existence of spirochaetes in tertiary lesions, so there are, relatively, few

2i)

AKCmV KS

.successful experliueiits of iiiociiliilioii of aiiiiiials from icitiary lesions.
Hott'maun has, however, succeeded in inoculating an ape from a gumma
occurring in a man three and a half years after primary infection. It
has already been stated that the Spirochaia PuUida is an organism
between a bacterium and a protozoon, and in spite of the divergent views
lespecting the classification of spirochaetes, there are, in my judgment,
more characters linking them to the protozoon than to the bacterium.
The Spirochata PaUida contracts, moves, and modifies its structure in a
manner difterent to a bacterium. The appearance of resting forms is
totally different, and they arise in a different manner to the spores of
bacteria (Prowazek). Again, the clinical aspect of affection from spiro-
chaete invasion differs from that of bacterial diseases, and conforms
especially to certain trypanosome infections. There is a periodicity of the
symptoms altogether unknown in bacterial diseases. Ilut, what has struck
me from my own personal experience and knowledge, is the great similarity
of the histological lesions of the nervous tissues of chronic trypanosome
infections, e.g.j sleeping sickness and dourine, to syphilitic and para-
syphilitic lesions. {Vide Figs. Plates II. and III.). The universal
perivascular infiltration of lymphocytes and plasma cells in the central
nervous .system was thought by Aissl and Alzheimer to be patho¬
gnomonic of general paralysis and syphilis, but I have shown that
t‘xactly the same occurs in slee])ing sickness. In the ttuil de euit of hors(‘s
an ataxic paraplegia occurs, and I have found posterior root degeneration
and sclerosis of the posterior columns in five cases of dourine sent to im*
from the Imperial Ifacteriological Institute of India by Dr. Lingard. In
all chronic try])anosome infections, r.r/., sleeping sickness and dourine.
I have found a marked hyper])lasia of neuroglia, and in experimental
sleeping sickness of apes, as I shall show you, this connective tissue hy])er-
plasia preceded the perivascular infiltration. Thus we see that in both
syphilis and trypanosome infections we have a hyperplasia of the fixed
tissue cell (‘lenients, endothelial and conjunctival, with little or no poly-
mor])honuclear reaction. ^loreover, Spielmeyer has obtained by experi-
jnenfal tryj)anosome infection of dogs, a lesion of the posterior columns of
the spinal cord simulating the ataxic lesion; he has also produced optic
atrophy. Again, there is a similarity in the fact that lymphocytes and
plasma cells are found in the cerebrospinal fluid of trypanosome diseases
of animals and man, r.//., slee])ing sickness. ^Ioreov(‘r, Levaditi has sliown
that, in point of view of sensibility in respect to haunolysing poisojis,
blood coi’puscl<\s, spiiochaetes and ])rotozoa constitute a homogeneous
group, and the spirochaetc's coi]'i*spr)nd in this respect inoi-e to the proto¬
zoon than flu* bacteria.

The study of all these dis»*ases is [)rimarily biological. The conta-

SYIMIILIS OK TIIK XKUVorS SVSTKM

21

^inm viviini is i\ livin^^ oicrinnsiu whoso iH*tivitios, like that of all livinjr
organisms, aro J(M’ solf-proservatioii ami the j)iostM vat ioii I ho specios.
The ohomieal toxin which tlio orfrmiism produces is to enahlo it to live
and inultij)ly. The spirocliaetos consist of ii viscid plasm covered witli a
nieinbrane which servos as a means of osmosis. This osmotic membrane
is a lipoid substance, like that which forms the membram‘ of the rod
cor])uscles, and is sensitive to hieimdysin^ substances.

The fact that rastellani has discovered a spirocliaete which he terms
S/j. PaJIlfhtId in yaws is of importance in showing that a spirillary
organism not quite morphologically identical with that of syphilis is
j)robably capable of producing a chronic disease in many of its features
not unlike syphilis. It might be argued that all the postulates laid down
by Koch have not been fill til led, and, therefore, that we have no right
to claim that the SpIrorJufta Pallida is the specific organism of syphilis.
'Phus tlie organism, although it has been grown in celloidin capsules,
has not been cultivated on an artificial medium outside the body, and
the disease re})roduced by injection of such a culture. Ihit the same
argument might be applied to certain establislied protozoal diseases, c.//.,
malaria and sleeping sickness. Dourine may almost be regarded as tin*
syphilis of eqnines, tor it is characterised by an infective sore on the
genital organs, affection of the nearest lymphatic glands, then infection of
tlie blood stream followed by successive eruption of plaques: and, as in
syphilis so in dourine and slee[)ing sickness, the juice of the lymphatic
glands, in a condition of acute swelling, shows the specific organisms more
readily than the blood films. The trypanosomes may disappear from the
blood entirely, even without the administration of drugs, and reappear,
giving rise to an irritating eruption of papules and fever, and the trypano¬
somes can be found in smears obtained by scarifying the pajmles more
readily than from smears of the blood. This was demonstrated by Lingard
in the case of mal de colt of horses, and by the French observers in a case of
sleeping sickness. So, also, in syphilis I have been able to find an abun¬
dance of spirochaetes in the secondary papules of the skin, although I was
unablo to find them in the same cases in the blood films [vide Fig. 7, Plate
1.). It is a remarkable fact that Xeisser was unable to inoculate animals
by injecting the virus into the bloo<l or into the organs; success was only
obtaineil by scarifying an epiblastic skin surface and rubbing in the virus.
This is preciscdy the seat of eruptions and pullulation. It looks as if the
organism, to perpetuate the species, must find its way out of the body
in the way it came in. Sir Patrick Manson (Huxley Lecture) expressed
the opinion that, by analogy, we must presume that all trypanosome
diseases are carried by some biting inseet which acts as alternate host.
Hut dourine sjneads in the same way as syphilis. It is quit('

‘>0

Alien IVKS

po.ssil)le I hilt the Try/mnosotud KtjuiperJurn, which ililVers vtny little
from the Trijimnnaoma Kvun.vi, moy ho tliis trypauosome which has
ucquireil the hal)it of pullulatioii in the jniUM>us cutaneous oriHct»s, ami
when infection occurs, always tends to get back there. In syphilis the
same habit may have been acquired. It is known that mucous tubercles
and condyloinata (secondary eruptions) are more infective than the
primary sore, and contain immense numbers of spirochaetes. Similarly,
ujK)u reading Lingard’s experiments, 1 find he mentions that tin*
'rnjjHifiosomu Equiperdum was found in great abundance sometimes in
the vaginal mucus when it could not be found in the blood. Again, he
was more successful when he inoculated animals by scarifying the
genitals and inoculating with blood from a paj^ule or with vaginal mucus
than when he injected the blood into animals. Those facts accord very
much with Neisser’s experiments, and would seem to indicate that a habit
had been acquired by the Tnjpanosimui Eptiperdum of developing in thi‘
mucous membrane of the genital organs and of using this acquired habit
as the means of preserving the species.

Tinally, the therapeutic agents, mercury and arsenic in the many
forms employed, are specific for both trypanosome and sj)irochaetc
a Sections. They are not of much use for bacterial infections. Alercurv,
particularly in the form of inunction, is especially valuable, and thi-
may be owing to the fact that it prevents the pullulation of the spiro¬
chaetes on the surface of the body, including the mucous orifices, a
habitat which these organisms have found particularly favourable for
jierpetuation of the species by transmission to another individual, iler-
cury, moreover, administered in any way, tends to come out by the skin,
as can be readily demonstrated.

I have pointed out that, practically, the morbid tissue changes in
syphilis are similar, whether the lesion be the primary sore or a gumma
twenty years later; moreover, it is difficult to understand how the spiro-
clieete, seeing that is has hardly ever been found in tertiary lesions, can
produce the same specific cell hyperplasia so long after the primary
infection. The following hypotheses may be put forward to explain the
jilienomenon of a gumma appearing spontaneously in the central nervous
system long after the primary sore and apparent cure of the disease: —

1. The spirochaete, or some modified form of it, has remained latent
in the tissues at the seat of the lesion, and, for some reason, inherent or
otherwise, the resistance of the tissues at that particular spot has be¬
come lowered, and the organism has exerted again its specific activity -
possibly in some not yet discovered intracellular form.

2. The specific organism has remained latent in some otlier tissue,
e.q., the marrow of bone, the spleen or glands, and, escaping into the

SYPHILIS OF THE N'KUVOl^> SYSTEM

blood or lymph cireiilatioii, lias, liki^ a new growth, eiigembMvd a
metatasis, whieli has develojied and increased, producing a liyperjdasia
of the fixed tissue cell elements conjunctival and endothelial.

d. There may he varieties of specific spirochaetes, one of which may
have an elective alKnity for the central nervous system, as we know the
Tnjpanosoma Gamhieme has. It is difticult to differentiate this trypano¬
some from other forms by morphological appearances [vide Figs. 4 and o,
Plate I.) ; liow mucli more difticult would it be to ditlerentiate varielitv;
of Sjnrochata VaUidn.

4. The invasion of the body by the spirochaetes has altered the blood
and lympli biochemically, so that the tissue reactions to all causes which
would lead to injuiy may take on tlie specific character.

Thus a ))low on the head, vascular-stasis, or some inherent w(»ak spo;
may become the seat of a gummatous process. Although we are only
beginning to unravel tliese Inological problems, the evidence so far
appears to be in favour of the fixed tissue cell hyperplasia with subse-
i|uent necrobiosis and fibrosis being a reaction to the influence of tln^
specific organism. The fibrosis may be regarded as the attempt on the
jiart of the tissues to repair the damage done in the struggle between
the specific virus and the tissues; it is accomplished by the young con¬
nective tissue cells which have survived the fray; these are converted
into fibroblasts and eventually into sclerous fibrous tissue. The amor-
jihous caseous material is the residuum of the dead cells and organisms,
especially the former, which, owing to the toxic influence of the virus
and the cuffing off of the vascular supply, have undergone nucleolysis
and plasmolysis. The organisms, when found, are not discovered here
when the struggle is past, but at the growing edge, where the new blood
vessels and ombiyonic cell hyperplasia is most active; for it is here that
the organism finds pabulum for its multiplication.

24

AU( HIVKS.

TLATK I.

Fic. 1.— Sj)irorhfpta PoV'Kht i?i smear j>ro|>arati()ii of ooiidylomn, stained h}' (liomsa solution.
Magnificat ion ;l. HM).

Fi<;. 2.—Another |•<•^tion of the <moar showinur a]^|)('aranr(‘'^ of two s|ii!n<*haotos twisted around
one anotlier : possihly this is the K'sult of lonLo’i ndinal fission. Magnification 3.400.

Fit;. SntriH'ho'tn PaUithi from smear preparation of mneoiis Inherclc. Mairnifieation I.SOO.,

Fn;. 4. — Section of spleen from a ease of eons/enital syphilis, staiiml by I.evadifi metho<l.
Maj^nilicat ion 1.400.

Ffo. 5. - lUoo<l smear from a ease f)f sleepin<j^ sickness, slimvinir 7V//y*. <inmhirnst\ Maf?nifieatioii

2.0(K).

FlO. 6. - blood film show'inLT Irup. Jfnicei. MaLoiifieation 1.700.

Fio. 7.—Section, showing spirochaetes. of a papule i>f skin from a ease of secondary syphilis,
before mercury was administ<Tcd. Stainctl l)y Levaditi niethotl. Ma^nitication 1,(100.

It will be nbscrv(‘d th.at it would be ditlicult to decide the nature of the two trypanosomes
by morphoIoLo’cal <*haraettTs alone.

SYriIILlS OF THE NERVOUS SYSTEM

25

I’LATK II.

Fig. 1.—Section of a small vessel showiic^^ the sheath inliltrated with lymphocytes and plasma
cells, and with proliferated ‘.dia cells. Exp(*riniental sleepimr siekne.‘>^s in an ape.
Magnification 320. ((’f. Fig. 3, Plate III.)

Fig. 2.—Section of cortex core«)ri from a case of sleeping sickness in a European. Staine<I to
.show the neuroglia. Magnificati»)n 450.

Fig. .3.- Section of brain of ape infected with 7V//y;. showing perivascular neuroglia

cell hyperplasia. Below are seen a series of neuroglia cells in various stages of develop¬
ment. Magnification 32o. ((’f. Fig. 4. Plate III.)

Fto. 4.—Periva.^'cular infiltration with lymph(K\vtcs and jjlasma cells fr«»m a ca.se of gummatoiM
(•(‘rebrospinal meningitis. Stained by polychrome blue. Magnification 250.

Fig. .*>.—Section of central nervous system from a case of sUu^[>ing sickne.ss in a European,
showing periva.scidar infiltniti«)n witli lymphocytes and plasma cells. Magnification 2.‘iG.

26

\R( HI\ KS

ri.ATK III.

Fig. 1.—Photoraicrograph of a .section of the aseemling parietal convolution in a case of tal>o-
paralysis of four years’ duration, showing a small vein surroundetl by plasma cells, w^hich
are lying in a dilatcNl lymphatic. The vessel at another part had ruptured and fille<l the
lymphatic sheatli with blood corpu.scles. Some of the large swollen cells showed in
their interior the blood pigment in various stages of destructive disintegration ; they
appear to have, therefore, a phagocytic function. Nissl stain. Magidficatioii r>00.

Fig. 2.—Section of syphiloma of the brain showing vessel with (r) thickened endarterium. (/)
lymphoc*ytes, (p) pla.sma cells. Magnification 3(K).

Fig. 3.—Section of small subcortical vessel, acute general paresis. (/) lymphocytes, (/;) plasma
cells. Magnification 300.

Fig. 4.—Small vessel, acute genenil paresis, showing neuroglia cells with proliferating nuclei
and processes exten»ling on to the small vesstd. As in sleeping sickness there is little or
no infiltration around because there is no pial nr lym[)hatic sheath. Magnification 400.

Fig. 3

Fig. 4.

fnvr f). 26 .

SVl'IilMS or rilK XKKVOl S SVSTKM

Lkcti UE IT.

Ill luy last lecturr 1 oiuloavouml to point coil soiiir facts and liypc-
tlicscs of tlic biological probliMiis of syphilis, especially in relation to
disease of t!u* nervous system. To-day 1 wish to draw your attention to
modern researches hearing upon the hio-chemi(*al ihanges which occur
in the tissues and fluids of the body as a result of the entry and per¬
sistence of the sy[)liilitic virus in the body.

I must, liowever, first make a slight digression, in order that you may
obtain a better understanding of the altered bio-chemical conditions;
this digression refers to the nature of lipoids, substances wliicli hav*‘
recently, in connection with luemolysis, attracted a great deal of atten¬
tion (and I wish here to acknowledge my indebtedness to Dr. llosenheim
for valuable information). “There seems to be a good deal of truth in
the opinion of Jhing that the importance of protein as carriers of lifi‘
(“ Triiger des Lebens ”) has been over-estimated, while that of the lipoi<ls
has been neglected.Pfliiger, and most physiologists, have taught that
the vital activities depended essentially upon proteins. Dang contested this
(‘xclusive view. Tin* name lipoid was given by Overton to fat-like sub¬
stances *whicb are contained in the cells of all living things, animal .and
vegeta ble. They were named by Waldemar Koch, lecithans, but tin’s
name has not been adopted. The.se lipoids may be divided into three
grou])s (1) N. and P. free Cbolesterin, fatty acids, and lipochromes:
(‘Jj Nitrogenous but P. free (’erebrosides; (•>) Phosphatides containing
both N. and P.; of these, tire most important are the mono-amino phos-
])hatide lecithin and the di-amino-phosphatide sphitKjomi/eHn.

These lipoids were, until recently, considered of little, importance;
in fact, cholestrin was looked upon as a physiological curiosity by virtue
of the fact that its cry.stals had a chip out of one corner, and little else
was said about it except that it was contained in the red blood corpuscles
and formed the principal constituent of gall-stones. Lecithin was known
to be a con.stituent of the red corpuscles, but it was not until Flexner and
Xognehi's experiments on cobra venom had been published that the
importance of these bodies in the action of toxins aroused attention. They
found that cobra venom contains two poisons, a neuro-toxin and a globulin
which has the property of dissolving red corpuscles. If, however, they
washed the red corpuscles free of serum, the cobra venom no longer had a
luemolysing action; but, on adding serum to the washed corpuscles, an
addition of the cobra venom produced hoemolysis. Clearly something was
contained in the serum which interacted with the venom to produce the
result. Kyes showed that the activator is soluble in alcohol and in ether,
and he finally identified the substance as lecithin. But cholesterin, another

2S

A lull IV KS

li]M)ul, has tli(‘ projXMty ol' foiiiiterac'tin^ the activating (‘hect ol‘ lecitliiii
on cohra venom. This antaf^onism of cholesterin and lecithin j)oints
some bio-cliemical or bio-pliysical relationsliip between the two bodies.
Moreover, this relationship as re;^ards osmotic membranes and liaemo-
lysis has been experimentally put to the test by Panucci. This observer
constructed glass cells covered with a membrane impregnated with lecithin
and cholesterin; in these he placed Inemoglobin solution and then sus¬
pended them in the toxin solution ; the hiemoglobin behaved differently

{n) XoniiMl l»ln(Kl with osiimtic nK*ii)l»raiK* t<' ions of Xa. K. ('a.

(A) ('liciiiical explanation <»f h;L*uinl\-is dissolution of osmniic ineniltrane and csi-ape of
lia*nioLdol)in.

(fi IMivsical cxijlanati**!! <»f liieint >1 \-is l>y a l>io-)»}iysic;i| alteration of tlic <»snH»tu’ nieni-
iiiano. l>y wliieli it l»eef»m»‘s peinieaMe to ilu- lariro lia innydoltin inoleenh*-.

SYPHILIS OF THE NKKVOIS SYSTEM

29

(as regards diltiisiun) according to the proportions of these substances in
the membrane. If we regard the red blood corpuscles as consisting of a
sponge-like protein stroma holding the luemoglobin in solution, the whole
being covered with a membrane consisting of a properly adjusted complex
of the lipoid substances, cholesterin and lecithin, then we may suppose
tJiat htemolysis occurs as a result of a chemical or physical disturbance of
the balance between the cholesterin and lecithin. In haemolysis the mem¬
brane is either dissolved by the action of a ferment or a physical change
occurs in the membrane, by which it becomes permeable to the large
luemoglobin molecules, whereas in its natural perfect state it will only
allow the smaller ions, Ca, Na, and K, to pass through. (Fig. 1.) It is
probable that all cells and unicellular organisms possess similar osmotic
membranes, and that the lysis of these organisms depends upon physical
or chemical changes, in the osmotic membrane which is termed a peri-
plasium. The importance of this question is obvious in regard to cytolysis,
bacteriolysis, and protozoolysis, and it will become especially apparent
when we come to the study of the Wassermann reaction of the deviation
of the complement in the sero-diagnosis of syphilis.

In regard to the origin of lipoids, especially in pathological con¬
ditions, it is necessary first to refer to an important paper by Munk
just published. This observer has used the polarising microscope to
distinguish between fat and li])oids in cells; the latter are doubly
refractile wlien the Xicol’s ])rism is rotated. Ambrose and Held
made use of this metliod for determining the existence of the myelin
slieath in tlie anterior and posterior roots of the embryo. Munk
Knds that the existence of lipoid droplets in the cell is associated with
dissoluticn of tlie nucleus and destruction of the cell. Rosenheim ivinarks
that the pliosphatides may form a link with the cell nuclein which
possibly obtain their necessary supply of pliosphorus from this source.
A lipoid substance in great abundance, then, means cell dissolution;
the nucleus highly charged with phosphorus and the cell protoplasm
break up into a lipoid complex as a result of the nucleolysis and
plasmolysis. It may be suggested Lovaditi’s experiments show that
the spirochaetes stimulate the fixed tissue, cells to ])roliferate, and
then, invading this bed of young cells rich in nuclein, they, by tlie
action of some secretion or otherwise, cause these same embryonic cells
to undergo lysis, thus providing the necessary pabulum for their own
growth and proliferation. It is probable these young cells -are more
(‘asily attacked than the older cells, and this may be the reason that the
spirochaetes are found in such great abundance in fodal tissues, and why
the fmtal tissues, especially the liver, contains such an abundance of
lijiuid substance serving for the Wasseiniann reaction, although chemi-

30

AECHIVES

cally il does not dilier from lipoid substance which can be obtained froni
normal tissues.

We are now in a better position to consider the serum diagnosis by the
Wussennann and other methods dependent upon bio-chemical changes
induced in the body by the introduction of the syphilitic virus whereby
immunity to future inoculation is e^itected; and which, in my opinion,
lies at the root of the late degenerative processes occurring in the central
nervous system, and which are collectively termed parasyphilitic.

Although it has now been ascertained that the syphilitic virus in¬
duces in the body metabolic changes whereby larger amounts of lipoids
occur ill the serum, and also in the cerebrospinal fluid in general para¬
lysis and tabes, yet these same lipoids are found in the normal tissues
and fluids, the specific character is manifested by ([uantity ralher than
(jiuility. The substances which in hopinolysis play the part of antigens
are lecithins, combined with other substances, especially soaps (Rondoni
and Sachs), and those which play tJie |>aid of antibodies are possibly com-
jilexes of lipoids and globulins. Yet, although in describing the Wasser-
mann and other methods and the evolution of the knowledge concerning
the same the terms antigen and antibody will be used, it is better to stat<‘
at once that they do not conform to the antigen and antibody of bacterio-
lysins, and that the deviation oi the complement (or fixation of the com¬
plement) may possibly depend upon the presence (»f those two kinds of
lipoids, which we have previously se(*n play sueh an imj)ortant part in
the action of cobra venom.

Tiik Skki m l)iA(f\()sis or SvriULis nv tiik AVasskumanx Method.

To explain the principles of this method it is necessary to make a
few introductory remarks regarding its origin. Bordet, in 11)01, discovered
the phenomenon known as the absorption or deviation of the coniple-
ineiit. At about the same time Gengou discovered a similar phenomenon
when working with precipitins. AVasserniann, Xeisser and Brtick,
Ticvatliti, Citron, Plant, Stertz and others have a])plied this method of
llie absorption of the complement of liordet and (jengou to the diagnosis
of syphilis by the existence of syphilitic antibodies and antigens in the
blood serum and cerebrospinal fluid of persons sufVering with primary,
secon<larv and tertiary syphilis, as well as in the post-syphilitic, paru-
syphilitic (or late syphilitic) affections, viz., tabes and general paralysis.
The epoch-making experiinent of Pfeiffer on bacteriolysins may be said
to have afforded the foundatif)n of our know](*dge of the principles
governing immunity. Bordet, by liis observations, canu* to the conclu¬
sion that bacteriolysis by tin* serum of an immunised animal was due to
the presence of (wo substances, the one destroyed l)y heat (thermolabile)

SYPHILIS OF THE ^EKVUCS SYSTEM

31

present in normal serum, the other (tliermostabile) a substance which
resisted heat (50^ C.) and was only present in the body fluids and blood
of an immunised animal. The former is called the cytase or complement,
the latter the immune body or antilKKly (amboceptor, Ehrlich).

liordet and others, by experiment, found that if the corpuscles of one
animal were injected into another of a difterent species, these corpuscles
disappeared with the priHluction in the serum of a specific hiemolysin
analogous to the bacterioh sin; the haemolytic properties of the serum
being due to a specific antibody (immune body) linking up the cytase or
complement to the corpuscles. This important discovery led to the
possibility of the study of the theory hi vitro and its practical
application to the diagnosis of disease. The same principles deter¬
mine the production of haemolysins as bacteriolysins, and the solution
of experimentally sensitised corpuscles can be used as a precise
index of the presence or absence of one of the two unknowns, viz.:
(1) the antigen; (2) the antibody or immune body. The thermo-labile
substance cytase (Bordet) complement (Ehrlich) is contained in normal
serum. Bordet holds that there is only one complement in normal
serum, and, contrary to Ehrlich, that it is not a si>ecific substance for
each antigen, but specific for each animal. Bordet has introduced the
terms antigen and antibody, the former to signify any substance wdiicli,
when injected into an animal, will cause.the production of an immune
serum; the latter to denote the antagonising substance produced and
which is the essential for the immunising action of the serum. Now, if
eitlier the antibody or the complement be not present, or be removeil,
the specific bacteriolytic or haemolytic action of the serum or fluid is
lost. Again, if the antibody in the presence of the complement is linked
up to the antigen, both the antibody and the complement will be inac¬
tivated. To find out it a given serum or fluid, c.q., cerebrospinal fluid,
contains either the antigen or tlie antibody is by the experimental induc¬
tive method known as the dwidtloo of t/tr mmjilcincnt. How is this
eifected ?

AVe require first to immunise an animal against the blood of
some other animal; tor this purpose the blood corpuscles of a sheep are
injected into the circulation of a rabbit. The blood serum of the rabbit
is thus made hieiiiolytic to the corjiuscles of the sheep by virtue of an
immune body [jIus the normal complement or cytase. The latter can
be removed by lieating to 50^ (’. for 30 minutes without destroying the
former. Wa have thus the immune body, which by itself will not
dissolve the washed corpuscles of the sheep. If, however, we add tin*
normal serum of a guinea pig, the ambocejdor or immune body links up
the complement or cytase and the corpuscles are dissolved.

ARC’HIVKS

32

The second part of the experiment is i!ie deviation of the complement
or its neutralisation, so that liajinolysis no lonjtfer takes place when the
serum of the guinea pig is added to t!ie immune body and the washed
sheep’s corpuscles. This is effected by the presence of both antigen and
antibody in the fluid to be examined. The serum, or cerebrospinal fluid,
to be examined is mixed in varying dilutions with a watery (or alco¬
holic) solution of the liver of a syphilitic betus, which will contain tin*
antigen (lipoid). A small amount of the s(*rum of a guinea-pig is tlieii

( 1 ) {- 2 ) {;])

Kk;. - 2 .

(It ( ol |';ir;i]\.-i." >lin\\ ini' llir <'ii

1 riMii I lie inniliatnr.

CJ) Ditto, >l;in<lirii^ <t\ ( t nii''lil ud jc,.,

(•») ( oiiiinl witli norin.il i*fr«‘l»iti>|iinal tliii«l. .'•Imw ini' tMl:il lin ini>1 v-i-.

SYPHILIS OF THE NERVOUS SYSTEM

33

add€<l and the total volume made up to 2 cc. with saline solution.
The series of tubes containing these mixed solutions are placed in
an incubator at 37^ C. for one hour, and then the sensitised blood
corpuscles are added. (By sensitised corpuscles I mean washed
sheep’s corpuscles in immune rabbit’s serum which has been heated.)
The mixtures are again placed in the incubator for two hours at 37^ C.,
then taken out and put on ice over night. Tlie next morning the
amount of haemolysis in each tube is estimated (vide Fig. 2). If, on the
one hand, antigen and antibody have been present they have united with
the complement, and no solution of corpuscles will have taken place
because the complement is fixed ; if, on the other hand, the immune body
(antibody) was not present then the complement (cytase) has remained
free to act upon the sensitised corpuscles and lead to their solution. A
control experiment, using a normal serum, or cerebrospinal fluid, viz.,
one which contains no antibody, must be used at the same time.

In the hands of nearly all trustworthy and experienced investigators
ibis method introduced by Wassermann has yielded most valuable results
as a means of diagnosis. It is claimed even tliat it is more reliable than
the Widal reaction for typhoid. Plant obtained a positive reaction in
80 to 90 per cent, of undoubted cases of syphilis by this method. He
found the reaction specific; it is not definitely present in a non-syphilitic
individual; it enables a diagnosis of the constitutional disease to be made
but not of the organ affected. He did not obtain the reaction with the
cerebrospinal fluid in 25 cases of syphilis in which the nervous system was
not affected, while the serum as a rule gave a positive reaction. This was
not to be expected from what has already been said as regards the cerebro¬
spinal fluid and its secretion. It shows that the reaction depends upon
the production of some substances by the tissues of the nervous system
themselves. The nature and origin of that substance will be discussed a
little later, but reference will now be made to the remarkable unanimity
of opinion of all those who have made experiments upon this subject as
10 the almost certainty with which the cerebrospinal fluid of general
paralytics and, to a less degree, tabetics give this Wassermann reaction.
According to Plant the reaction may be negative with the cerebrospinal
fluid in cases of syphilis of the nervous system, but he obtained a positive
result in 94 out of 95 cases of general paralysis with the cerebro¬
spinal fluid, and in every one of the cases the serum gave a positive
reaction. In cases of cerebral sj’philis the serum was usually positive
and the cerebrospinal fluid usually negative; in 70 to 80 per cent, of
the cases of tabes the cerebrospinal fluid gave a positive reaction. Citron,
G. Meier, W. Fischer and G. Meier, Micliaelis, Weygandt, Fleischmann
and W. J. Butler and others have obtained similar positive results by

34

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this method. At my suggestion, my assistant, Dr. Candler, in conjunc¬
tion with Dr. Henderson Smith, of the Lister Institute of Preventive
Medicine, has been engaged in applying this reaction to a number of my
cases in the hospital and the asylums, with the following results: —

They have now examined the cerebrospinal fluid of 100 cases, of which
94 were asylum cases and six were in general hospitals. Forty-six cases
of general paralysis were examined, 41 of which gave a positive reaction
by the Wassermann test, a percentage of 89*1. The reaction was not
obtained in any of the control cases. Two cases of locomotor ataxia
failed to give the reaction, but it may be noted that neither was in an
active stage. A negative reaction w as also obtained in a case of syphilitic
meningitis in which the cell contents of the cerebrospinal fluid were
diminishing rapidly in numbers under specific treatment. It is also
interesting to note that cases of tubercular meningitis failed to give the
reaction, although in one case the cerebrospinal fluid contained a large
number of leucocytes per cubic millimetre {vide Table).

AN ANALYSIS OP THE RESULTS OF THE WASSERMANN-IM.A UT
REACTION ON THE CEREBRO-SPINAL FLUID OF lOo CASES.
Table I. —Showing the Results of 94 Asylum Cases.

No, of

Cases.

Waeser-

mann.

+

Wasser-

mann.

Per¬
centage of,
+

reaction.

No. of
cases con¬
tinued by
an to pay.

4\jtal miiiihe!* of cases (>f—

Ceueral l*arulvsis, examined during life .

. >

88-9

ft

(H) .. .

d

—

d

__

NoiidJeiieral paralysis „

Id

—

Id

_

Locomotor ataxia ,,

Insanity, examined during life (by lumbar

o

.)

- --

iniiictnre)

dd

—

■—

—

—

(ieneral paralysis (post mortem)

I

1

100 - r

Non-deneral ,, „

21 !

—

1

—

donlithd

4’otal number of cases exaininerl—

Post mortem

i

—

—

—

During life and post mortem

Total number of cases of general imralvsis, i

!»!•

^ 1

t

1

—

examined during life and post mortein I

-l-d

1

Id

r)

1

89*1

—

* In Bix of the above 42 cases of O.P.I., the serum obtained from the blood, withdrawn durine life cave
a positive Wassermann reaction. o ’ fc

t The C.S.P. of the four cases examined (post mortem), trare a similar result with the Wassermann
Test as during life.

SYPHILIS OF THE NERVOUS SYSTEM

35

Table II.—Showing the Results oe t) Control Hospital Cases.

I . . 1 I Wa.s8er-

No. Institution Nature of Case. I mann

I I reaction.

1 Charing Cross Hospitiil... . 'Tiil)erc\ilar Meningitis. (P. M.) ... ! —

2 I „ „ . . . Cerebellar tumour (totally blind.) (P. M.) j —

t „ „ .. .Sy|>hilitic meningitis— —

I I 1st examination, cell count 70 per 1 c.m. |

I ' 2nd 'H} i

I I Victoria Hospital Tor Childi'en ..! Tubercidar meningitis ... ... . | —

^ " .i

b ^ Charing Cross Hospital... . ,, ,, ... . .. —

! (1 c.m.—iOO leucocytes, 8 lymphocytes}. .

I wish here to acknowledge the kind assistance which has been
rendered during this research by Dr. Hobert Jones, the Medical Superin¬
tendent, and Dr. Hughes, Medical Officer of the London County Asylum
at Claybury; Dr. Bond, the Medical Superintendent of Long Grove
Asylum ; Dr. Ingram and other medical officers of the London In¬
firmaries; Mr. Gibbs, Surgeon at the London Lock Hospital; and Dr.
Nepean Longridge, of Queen Charlotte’s Lying-in Hospital for Women.

For the purpose of diagnosis, therefore, especially of general
paralysis (Fig. 2), it is a very important addition to clinical methods.
Since its application, however, many doubts have been cast upon the
interpretation of the facts whether indeed the reaction is in any way
due to syphilitic antibodies.

Levaditi and Yamanouchi made a study of the diagnosis of syphilis
and general paralysis by the Wassermann method. The results of their
researches are very favourable from the clinical diagnostic point of view.
Levaditi and Marie have demonstrated the facts that normal liver can
replace the syphilitic liver in the preparation of the antigen, and the
cerebrospinal fluid of general paralytics supposed to be rich in anti-
l)odies is devoid of spirillicide properties. These facts show that the
sero-reaction in question, although clinically a specific test for sypliilis,
had nothing to do with syphilitic antigens and antibodies. Moreover, the
active substances of liver extract, syphilitic or normal, contrary to the
true antigens, are soluble in alcohol; and the sero-reaction can be
obtained with bile salts and with lecithin, or with soap (Sachs and
Altmann), cholesterine and vaselin (Fleischmann), although more feebly.
The sero-reaction of syphilis and of general paralysis is the same, and is
not due to the intervention of antibody or syphilitic antigen in the usual
sense of the word, and has no relation witli U\e Spirochceta pallida. Land-
steiner and Forges have also demonstrated that the extract of the liver

c 2

36

archives

owes its particular properties for this reaction to the presence of lipoids
and bile salts soluble in alcohol at 8U^ C. These products are found not
only in the liver but also in different organs of man and animals. Laiid-
steiner, Muller and Potzl state that in syphilitic serum substances are
present which in the general sense are not anti-syphilitic bodies but
which bind up with certain constituents of normal and syphilitic tissues.
Moreover, thev assert that the blood serum of animals infected with
Tryp, equiperdum and Tvyp. Gainhit use contain similar substances which
they have called hidaffines. Yet being a characteristic reaction, it is
attributable to the presence in the serum and in the cerebrospinal fluid
of certain at present unknown compounds, which in the presence of bile
salts, soaps and lipoids of the liver precipitate and determine the fixation
of the complement. Levaditi and Yamanouclii consider that these
compounds arising in the organism itself may bc‘ a cliolesterin ester.
Thus it will be seen that these authorities give a new interpretation to the
phenomena of the Wassermanii method, which, however, in no way
militates against its value as a practical method of diagnosis.

Tliey also assert that there are between normal serums and lipoids of
the body and speciHc serums and liquids, only quantitative and not
f[ualitative differences; the reaction of Wassermann is provoked by his-
togenic and not bacterial substances. They find, moreover, that lipoids
serving for sero-diagnosis not only exist in the liver but in other organs,
the brain, the corpuscles of the blood, etc. They are probably complexes
in which lecithin largely enters into the composition.

Levaditi, liavaut and Yamanouclii have proved that wlien syphilis
leaves intact the central nervous system, although the serum gives a
positive reaction the cerebrosjiinal fluid does not, and this is what one
would expect. It is, however, different when the central nervous system
is affected even in a slight degree. The cerebrospinal fluid can then
ac([uire properties which enable it to jdeld the Wassermann reaction.
In fact, in the four cases out of the many examined presenting nervous
symptoms, which were neither tabetics nor paralytics, tlie fluid has twice
given a positive reaction, although quite feeble. The method of fixation
of the complement would up to a certain point then scu ve for the early
diagnosis of syphilis, esjiecially when the brain is affected.

The researches of tlie above-named authors sliow that there is not
any paralhdism between the results furnished by the cytological examina¬
tion and those obtained by the Wassermann method. The leucocyte
reaction may be very marked in certain secondary sj)ecific cases without
the cerebrospinal fluid being in the least abU^ to fix the complement.
Such was the case in one of my patients with well-marked syphili^*c
cerebrospinal meningitis. This patient was a woman, aged 34 years,

SYPHILIS OF THE NERVOUS SYSTEM

admitted, under my care at Charing Cross Ilospital, as a case of tabes.
Upon examination I diagnosed cerebi'ospinal syphilitic men in git is
(pseudo-tabes). Lumbar puncture was performed, and the fluid was found
to contain 370 lymphocytes per cubic millimetre; she was put on mercurial
inunction, and in a fortnight she had greatly improved, i'he lymphocytes
were now only 70 per cubic millimetre; a fortnight later the lymphocyte
count Avas 20 per cubic millimetre, and she was well enough to be dis¬
charged, nearly all the symptoms having disappeared. The Wasser-
mann reaction was negative on the last two occasions, when lumbar
puncture was perfonned; it was not tried in the first instance.
Tlie existence of numbers of lymphocytes in the spinal canal
does not necessarily entail the appeamnce of substances which in
the presence of lipoids engender the phenomenon of Wassermann.
Marie and Levaditi found that there is a pamllelism between the
rapidity of progress of general paralysis and the degree of intensity
of the Wassermann reaction, with which observations tlie results of
Drs. Ilenderson Smith and Candler are in agreement; no doubt, there¬
fore, there is a connection between the breaking down of nervous sub¬
stances (destructive metabolism) and tlie amount of this complex
lipoid substance, with wliich probably the reaction is associated and upon
which it in a measure depends. I have been attempting to ascertain tin'
chemical nature of this substance but my results are not yet sufficiently
advanced to make any definite statement. However, I have found tbat
ilie blood and cerebrospinal fluid in parasyphilitic affections contain a
marked excess of lipoids, inorganic salts and splitting products of the
jiliosphatides; and that this excess is proportional to the intensity of tlie
disease. I have also found that a cerebrospinal fluid which gives a posi¬
tive Wassermann reaction, after removal of the protein content by pre¬
cipitation with alcohol, fails to give the reaction. I am therefore in
agreement with Kogucbi who, working on the relation of protein, lipoids
and salts to the Wassermann leaction, has come to the following con¬
clusions : —

1. The high value in respect, to coniplemenl-binding exhibited by blocvl sera from
syphilitics and spinal fluids from gt'iieral paralytics is associated with an excessively
1 igh content of globulin, but there dix‘S not exist a direct quantitative relation between
the tw'o. Case's of s<.‘condary syphilis wdiich have been under prolong'v<l and proper
medication do not exhibit the gh»bulin increase, and usually fail to give the
Wassermann reaction. The active substances entering into the Wassermann reaction
are precipitable with the glolnilin, and chiefly with the eiiglobulin fraction of the
fluids.

2. Temperature's of 70^ to C. destroy the active substances. Exposed to
sunlight, the active substances deteriorate slowly. A photodynamic substance sucli
as eosin, under the direct influence of the sun, brings about their complete and rapid

•38

ARCIfIVES

deslrnction. This effect does jiot m*rur in the dark. The active substances are
subject to tryptic an<i peptic diL»csti<)n, and are <lestr(»yed l>y weak acids and alkalies.

3. The active substances in the bhxKl sera and spinal fluids cannot l)e st^parate<l
from them or from the globulin precipiiato by alcohol.

4. There are containeil in the alcoholic extracts of normal ami syphilitic blood
and organs c'ertain acetone-soluble lipoids which jK>ssess high antigenic values for
the Wassermann reaction. Cholesteiin is inactive, and the bile salts less active than
the lipoidal bodies.

5. Sodium chedate is about as active as sodium taurocliolate, but neurin and
cholin are inactive.

Porges and Meier found that by addition of lecithin certain
substances contained in syphilitic serum are rendered evident bj’
a flocculent precipitate, and they have employed this method in
place of the deviation of the complement method. But it is generally
thought that this precipitation method is not so specific as the Wasser¬
mann method; moreover, Neubauer, Porges and Salomon were able to
show that syphilitic serum only behaves stronger in this respect than
normal serum. Fritz and Kren found that the lecithin test is not abso¬
lutely reliable, for non-specific diseases as tuberculosis, lepra, etc., give
a precipitation; still less reliable is the test with glycocholate and tauro-
cholate of soda. In respect to the Klausner reaction of globulin pre¬
cipitation it was found that it was more uncertain than the lecithin and
bile salts flocculation.

Neisser, Briick and Stern^s investigations are of importance, for they
have made a large number of experiments with apes and anthropoid apes,
as well as observations on human beings. They conclude that the antigens
are not identical with the living virus, nor of the same substance. They do
not consider that mercury and atoxyl cause a destruction of the antigen
but that treatment by these drugs injures or destroys the spirochaetes.
Moreover, it has been found that antibodies exist normally in small quan¬
tities in some of the lower apes; it has so far not been found in the higher
apes; it is therefore not a new product in syphilis but it is enormously
increased in quantity in this disease. They consider that the serum
diagnosis researches prove a direct association of syphilis, tabes and
general paralysis. Immunity to reinoculation occurs when the virus
has become generalised in the blood and lymph (Neisser). It is probable
that the generalisation of the virus engenders simultaneously changes
in the properties of the serum by which changes it becomes capable of
giving the Wassermann reaction and preventing re-inocnlation.

There are a number of other reactions which show that a profound
bio-chemical change occurs in the blood in constitutional syphilis. Thus
Klausner has shown that distilled water added to syphilitic serum causes a
j)iecipitution due to the amount of a precipitable globulin which syphilitic

SYIMIILIS OF TIIK NERVOI'S SYSTEM

3 !)

serum contains. Foriiet and Scliereschewsky liave shown that the serum
of paralytics and tabetics exclusively give with the serum of syphilitic
patients a positive precipitin reaction. It is claimed, therefore, by them
that this observation proves the syphilogenous origin of tliese two diseases.

The simpler method of Noguchi, to which I have been giving atten¬
tion, consists in boiling two parts of the cerebrospinal fluid with five
parts of a 10 per cent, solution of butyric acid in saline solution for
a few seconds and then adding one part of normal NaOH solution
and again boiling briefly. A flocculent precipitate is obtained in para-
syphilitic affections. It is due to the presence of a globulin ; it has
before been remarked that there is a parallelism between the presence of
albumin in cerebrosjiinal fluid and the Wassermann reaction.

Summary .—The original method of Wassermann is the most com-
plicate<l, but is regarded by the majority of investigators as the
most specific and reliable. Whatever may be the explanation of the
facts all the evidence goes to prove: (1) Tliat these methods in the hands
of competent observers afford a valuable means of diagnosis and are
especially useful when applied to the cerebrospinal fluid for the deter¬
mination of the existence or not of general paralysis. (2) That similar
substances, whether antibodies or not, occur in the serum of syphilitic
and parasyphilitic persons in such quantities as are not found in the
serum of normal persons or in the sera of people suffering with other
diseases. (3) That similar substances are found in the cerebrospinal
fluid of tabetics and general paralytics, and the amount of those sub¬
stances which cause a deviation of the complement or a precipitation ia
in proportion to the activity and length of duration of the disease; that
these substances are of tissue origin or arise from tissue destruction
caused in some way by the action present or past of the syphilitic virus.
(4) It is probable that the syphilitic virus excites an increased unloosen¬
ing of complex lipoid substances containing lecithin and cholesterin, etc.,
from the red corpuscles and cells of the body. (5) That this prevails
througl^ life, and in certain cases of syphilitic infection, viz., general
paralysis and tabes, the central neivous system, which under ordinary
circumstances is protected against the loss of its lipoid substances, takes
part in the process, and this is manifested by the presence of lipoids
and globulins in the cerebrospinal fluid, and these act as antibodies
in the reaction. This lipoid complex, as well as globulin, increases
in amount as the process of neuronic decay proceeds. It is probably
owing to the presence of these substances that the granulation
of the ventricles, so characteristic a feature of general paralysis, arises
as a result of stimulation to proliferative hyperplasia of the ependymal
epithelium. Choline may also be present owing to decomposition of

40

ARCHIVES

lecithin, but this may occur in any active degenerative process of the
myelin, and is not pathognomonic of any particular disease.

Other lipoids of the phosphatide group are present usually in con¬
siderable amount and in proportion to the extent of myelin destruction
and dissociation. I have pointed this out in the Archives of ^ieurology,
\ ol. II., 1902, p. 304, when after referring to the work of Flexner,
Xoguchi and Kyes on cobra venom I stated that: —

The products of degeneration of nervous tissues are numerous, and consist not only
of choline, but also of a number of bodies of the lecithin group, being various
derivations of “ protagon.” Choline is the most easily separated and recognised
physiologically and chemically, and it is possible that the jiroducts of degeneration
vary according to the cause and nature of the destructive in'tK’ess. Still, there is
no evidence to show that these products of Jegenoration can per s^i produce the
clinical manifestations and morphological changes indicating neuronic irritation
and destruction of general paralj^sis, otherwise we ought to get those changes in
other diseases, also destructive lesions oi the nervous system. Therefore, I think it
may be conceived as possible that there is a latent toxin in the bloo<i which combines
with endo-complements the products of deranged neuron activity, producing locally
(this is^ where the neuron metabolism is deranged either by stress, circulatory
deficiencies, or hereditary, physiological, or anatomical defects) an active neurolysiii
proportional to (a) the amount of latent toxin in the blood; and (6) the amount
of endo-complement produced by the deranged neuron metabolism.

Blumenthal state.s that he has found that the blood of syphilitic persons,
also of tabetics and paralytics, contains a large increase of lecithin as
compared with the normal. He finds also an increase of lecithin in the
faeces in tabes and general paralysis and a great decrease in the bone
marrow. He considers that tabes and paralysis are associated with a
progressive impoverishment of the body in lecithin. It is more probable
tliat there is an impoverishment of lipoids, including the important
substance, cholesterin.

Lecture III.

I endeavoured in my last lectures to indicate some of the advances
made in our knowledge of tlie biology and bio-chemistry of syphilis,
and in my final lecture I will try to correlate the facts with clinico-
anatomical knowledge, especially in relation to the etiology of the para-
syphilitic affections, tabes, and general paralysis.

Parasyphilis (Fournier) : Metasyphilis (Moebius).

Parasyphilis is the term given by Fournier to those diseases of which
syphilis is essentially the cause, but which are not directly the result of
the syphilitic virus. Such diseases are: general paralysis, tabes
dorsalis, tabo-paralysis and primary optic atrophy. These diseases

SYPHILIS OF THE NERVOUS SYSTEM

41

are really a single morbid entity owning the same cause;
insidious in onset, progressive in character, and uninfluenced by
anti-syphilitic remedies. These various clinical types of para-
syphilitic disease are the result of a primary neuronic dystrophy;
they have a similar pathogenesis and may occur simultaneously or suc¬
cessively in the same individual. In tabes dorsalis the spinal sensory
protoneurons are aifected; in general paralysis the cortical association
neurons; in tabo-paralysis both are affected simultaneously or succes¬
sively. The dystrophic process is due to a lack of durability of the
neurons; it may be a slow process of decay and death of the intra-spinal
portion of the sensory protoneurons, as in the case of tabes dorsalis; it
may be a rapid process of decay and death of systems and communities
of neurons of the brain, as in general paralysis. The former is a smoulder¬
ing destruction of neural elements, the latter a conflagration often fanned
into flames by microbial toxaemia, autotoxaemia, or circulatory disturb¬
ances associated with arterial anaemia and venous congestion with blood
stasis of the brain. It is probable that Erb's spinal paralysis and certain
cases of amyotropliic lateral sclerosis may be i)riinary post-vSyphilitic
dystrophies.

Fournier thus classifies parasyphilitic affections: —

I. Acquired Syphilis.

1. Acute hystero-neurasthenia of the secondary period.

2, Different neurastlienic manifestations of a more advanced stage.

d. Tabes.

4. General paralysis.

5. A special form of epilepsy.

0. A special form of muscular atropliy.

II. Heredo-syphilis.

Numerous dystrophic troubles, general or partial; malformation,
notably denial; arrest or retardation of physical and intellectual develop¬
ment, infantilism, dwarfism, inborn lack of vitality, cachexia, marasmus,
rickets, hydrocephalus, certain forms of simple meningitis in early life,
possibly certain cases of true epilepsy, juvenile tabes, spinal and optic
juvenile general paresis. The gravity of these affections lies in the fact
that they are uninfluenced by antisyphilitic treatment. The local and
general failure of development may be due (1) to the direct influence of
the virus upon the life and growth of the tissues, or (2) indirectly to
exhaustion of the specific energy of the cells of the central nervous
system by the establishment of an altered metabolism, the bio-chemical

42

archives

nature of which is not yet fully understood. But, as a provisional hypo¬
thesis, we might suggest that the unloosening of lipoid substances into
the blood, which we know occurs in congenital syphilis, may lead to a
defective vita yvopria of all the cells of the body. In some lesions of
congenital syphilis it may be actually due to the local invasions and
multiplication of the spirocliaete, for they liave been found in abundance
in situations where local lesions exist, the epiphysis of bone, and
why not in the epiblastic enamel geims.

We might provisionally suggest as a hypotliesis that in all cases of
acquired and congenital syphilis the living contagium (spirochaete) ex¬
cites the tissues and fluids of the body to a defensive reaction. The dif¬
ference in the elfect^ of inoculation may depend upon the virus itself.
Some striking examples will be given (p. 50) which apparently indi¬
cate that there may bo a special neurotoxic virus, and if such instances
were more numerous we could hardly believe that coincidence could
explain the facts. If, as there is reason to believe, the Spirochaia Pallula
is the living contagium, and tliat, becoming generalised in the lymph
and blood stream, it produces the secondaiy manifestations, then there is
a certain amount of chance what tissues will be attacked; for the living
agent, swept along in tlie blood stream, may become lodged anywhere,
and, by blocking capillaries, cause a local focus of tissue infection.
The existence of a generalised eruption implies virulence of the circu¬
lating blood, and experiments demonstrate the fact that the blood is
virulent during the eruptive stage; thus, Neisser has obtained a positive*
result by injection of blood into the skin in the chimpanzee, and Roux
and Metchnikoif have successfully inoculated a Macaque monkey from
the blood of a chimpanzee in the eruptive period. It would be of great
interest to know how long the virulence of the ‘blood persists after the
generalised eruption, or if the consecutive attacks which may occur even
after 15 or 20 years are explained by the “contagium vivum remain¬
ing latent in the lymphatic glands or some deep-seated organ. What
is the evidence in favour of this view? It is generally admitted that
the subjects of tabes and general paralysis are recruited especially from
those individuals who have had a mild attack and wlio very seldom show
any signs or symptoms of tertiary gummatous skin, visceral or bone
lesions. Fournier states: “The comparative mildness of the primary
constitutional symptoms in those who ultimately become tabetic would
almost seem to indicate that, when the syphilitic virus exj:)ends itself in
severe primary and secondary manifestations, there is a less tendency
to the subtle poison which proves so disastrous to the nervous system.'
From an oxpiu ienre of over 500 pod-mortem.^ made on paralytic patients,
I have been surprised at the rarity of severe tertiary skin and visceral

SYPHILIS OF TILL XKUVOUS SYSTEM

4;i

lesions as compared with the cases ot true syphilitic! brain disease.
Arterio-sclerosis, in the form of fibrotic placjues of the aorta, is, however,
very common in paralytic dementia, which, however, is now regarded as
a parasyphilitic affection. Again, although paralytics in the prodromal
stages of the disease often give themselves up to debauchery and sexual
congress with loose women, I have never seen or had my attention called
to a case of general paralysis among the vast numbers in the London
County Asylums that showed a primarj" sore or a secondary rash. Kratt’t-
Ebing noted the same fact, and concluded that the reason was that
every paralytic had had sypliilis and was therefore immune. He caused
this hypothesis to be put to a crucial test. Nine cases of general para¬
lysis were selected that gave no history and showed no signs on the
body; these patients were inoculated with the virus of a typical hard
chancre and watched for 180 days. They presented no signs of infec¬
tion. Th.e only assumption is that they were immune owing to previous
infection, and that they possessed a ^lower of resisting the action of the
syphilitic virus. The concordance of this result with the statistical data
of antecedent, inherited, or accpiiied syphilis in cases of tabes and general
paralysis given later, led to the widespread acceptance by neurologists
of the view that tabes spinalis or cerebralis (general paralysis) is essen¬
tially of syphilitic origin. No syphilis, no tabes. Only a few eminent neuro¬
logists, such as Von Leyden, nvfuse to accept the syphilitic origin of
tabes, and one of the arguments employed against this view is that anti-
syphilitic remedies are of no avail in preventing the disease or arresting
its progress. Moreover, we know that many people develop general para¬
lysis or tabes dorsalis, even though they have been treated with mercury
systematically from the primary infection onwards. vSo much has this
impressed some authorities that they have even asserted that over-
merciirialisation is the cause of the disease in question. The average
time which elapses between the primary sore and the onset of tabes and
general paralysis is, according to the observations of Schuster, the same
in persons who have been thoroughly treated with mercury and tliose
who have either not been treated at all, or only insufticiently. All the
facts, therefore, go to prove that the syphilitic virus has in some way
or other damaged the durability of the neurones, so fliat systems or com¬
munities die prematurely. It has been observed that Fournier includes
other functional and organic diseases of the nervous system among the
])arasyphilitic affections. We have less knowledge concerning them and
llieir pathogenesis. I have, however, seen cases of general paralysis in
which the motor symptoms were most pronounced and the dementia
slight, in which all the deep reflexes were exaggerated, and the plantar
extensor reflex present on both sides—a very unusual occurrence in the

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ordinary paralytic dementia. At the autopsies there was a well-marked
sclerosis of the crossed pyramidal tracts without any coarse lesion in the
brain and cord to account for it. I have also seen cases of progressive
amyotrophic lateral sclerosis occurring in the subjects of syphilis wliich
appeared to be the result of the progressive degeneration of the whole
motor efferent tract from cortex to periphery without any sensory dis¬
turbance. Some of the cases of Raymond cited by Fournier with sensory
troubles, viz., rheumatic pains and pareBsthesiae, are obviously, from the
account given of the appearances of the spinal cord post niortani casi^s
of sub-acute gummatous meningitis involving the roots. The serum
diagnosis and the examination of the cerebrospinal ffuid bio-chemically
and microscopically will permit us in future to determine whether
syphilis is the essential cause of these degenerations. For every nervous
disease, whether functional or organic, occurring in a person who has
suffered from syphilis is not necessarily syphilitic in origin, yet, when
we consider the profound influence the virus has upon the blood and
tissues of the whole body, it is not illogical to assume that any disease,
local or constitutional, functional or organic, occurring in a person who
has acquired or inherited syphilis may possibly have found a suit¬
able soil for development, owing to the diminished vital resistance of
the tissues, occasioned by such a potent and persistent poison as
syphilis. Thus syphilis, although not a direct agent in such a
case, by its devitalising influence and the impoverishment of the
lipoids, becomes an important indirect causal factor of the diseasi^
in question. There are many known ways in which syphilis can cause
functional disturbances of the nervous system and lead to the develop¬
ment of neuroses and psychoses. The theoiy of the possibility of the
syphilitic virus, or tlie lipoid products of its activity, stimulating the
neurons to increased dissimilative action and exhaustion has been shown
to have considerable support from recent investigations. {Vide p. 40.)
There are, however, other conditions which are well known, viz., the
change in the blood and blood vessels, and in the lymph and lymph
channels. Long ago, Virchow pointed out that in syphilis tliere is a
diminution of red blood corpuscles and a hyperalbuminosis. Later,
Schiilgowski, Hafter and Laacke described a considerable fall in the
red blood corpuscle count. In the secondary stage Martin and Hiller,
also Letzius, showed that not only is there a diminution in the number
of red blood corpuscles, but also an absolute diminution of the haemo¬
globin content of the corpuscle. Anz found, besides the fall in number
of the red blood corpuscles, an increase of the white, so that one can
speak of a relative and absolute leucocytosis. Later observers showed
that there was a diminution of polynuclear leucocytes, and that the

SYPHILIS OF THE NERVOUS SYSTEM

45

leiicocytosis was due to a great increase of lymphocytes, which increase
we may associate with the polyadenitis. Further, there is an increase of
eosinophils. These changes in the blood in the secondary period in¬
crease in intensity with each fresh series of syphilitic manifestations,
and diminish as they diminish; moreover, the blood changes disappear
with the disappearance of the secondary symptoms under anti-syphilitic
treatment. Fournier long ago described the favourable influence of
mercury upon the blood formation; clearly, then, the mercury, by its
influence upon the productiveness of the syphilitic virus, allows a return
of the normal haemapoietic formation, or arrests a too rapid haemolytic
action. The French authorities were the first to call attention to a syphi¬
litic anaemia, and to point out that iron had no influence thereon. The
ebb and flow of the amount of oxyhaemoglobin is correlative to the flow
and ebb of lympliocytes, which might indicate that, with the pouring
out of an abundance of lymphocytes from the lymph stream into the
blood stream, there was associated a pouring out of the virus that occa¬
sioned the irritation and hyperplasia of the lymph-cell elements. Hoff¬
mann asserts that he has observed the serum of a syphilitic patient pro¬
duce immobility and agglutination of the spirocliaetes. Perchance it
is that when the virus can no longer be neutralised by the defensive
reaction of the blood serum embolic capillaiy effects are produced, caus¬
ing papular eruptions of the skin, mu(‘ous tubercles, and occasionally,
meningitis. Selenew demonstrated blood changes before the outbreak of
the secondary exanthem, therefore before the secondary incubation stage.
It is probable that before the eruption becomes visible, microscopic
changes have occurred in the affected cutaneous capillaries and adjacent
skin structures, much in the same way as in the primary
sore; 'consequently, we should expect a blood change to precede the erup¬
tion. The anaemia may be due to a haemolysis owing to an unloosening
of lipoid substances (lecithins and cholesterin) from the red corpuscles by
the action of a toxic substance of the virus acting as a lipolytic ferment
disintegrating the osmotic membranes or by chemical interaction in the
lecithin and cholesterin complex, forming the osmotic membrane* pro¬
ducing physical changes by which the membrane becomes permeable even
to the large haemoglobin molecules. (Fig. 1.) It may be supposed that th<‘
protein stroma of the corpuscle is covered by a film or membrane formed
of this lipoid substance, and the virus acts upon it in such a way as to
dissolve, dissociate, or destroy the membranous film covering the cor¬
puscle, and causing thereby a liberation of both the haemoglobin and the

* The idea of the existence of an osmotic membrane was first conceived by T*rof. Schafer, as
far as I know, in the description of the blood. (Quain’s Anatomy. 1893

He pives many facts in support of his arpumonts in favour of the existence of such a
membrane.

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lipoid substances into the serum. According toLevaditi and Yamanouchi
the lipoids serving for serum diagnosis not only exist in the liver but in
other organs, the brain and the red corpuscles. They are probably com¬
plexes in which lecithin enters largely. The aiuemia may, however, be
due to interference with the functions of the haemapoietic tissues; in
support of this is the fact established experimentally by iS'eisser that the
red marrow and spleen are especially rich in the virus. Since mercury
can rapidly impiove this blood dyscrasia, it is probable that it does so
l)y arresting the development of the amtanixim vivum in these blood-
forming tissues. In congenital syphilitic children hieraoglobinuria may
occur, and this may be due to the existence of a large quantity of the
virus in the blood causing haemolysis of the corpuscles. Many authori¬
ties working at the subject of metabolism in syphilis have shown that the
nitrogen metabolism is altered. “ Von Boick, Stephanow, and Bjelakow
found that the assimilation of nitrogen of food sinks, and the percentage
of extractives increases considerably in relation to the urea.” (Max
Nonne.) This would indicate an altered dissimilative metabolism.
There is, therefore, considerable evidence to show that causes exist which
render the organs of the body more vulnerable, not only to other infective
agencies, e.//., tubercle causing scrofula, but also to the evolution and
development of neuroses and degenerations by a devitalising influence on
the tissues by the unloosening of lipoid substances. We have now to
consider how far do these researches, biological and biochemical, help
us in determining the etiology of tabes and general paralysis.

Etiology of Tabes.

(^I'ahcs DormUs, T(ihei> Opiicay (re/irral Paralysis)

The Wassermann method of diagnosis has come to stnmgthen and
confirm the belief of many neurologists like myself: n(f syjjhilisy no
tahcs ; ” this was previously based solely upon statistics and observations
relating to the etiology of the disease. Moreover, the etiology and the
serum diagnosis are reciprocally supporting not only of the parasyphilitic
theory, but also of the view that there is one morbid entity which may be
described as tabes; a view first put forward by Fournier, and which I
have supported by comparing the clinical notes, and in a large number
of instances the posUmoviem results (with microsco])ic investigation) of
sixty cases of tabes dorsalis and sixty cases of tabo-jiaralysis. T came
to the conclusion that Fournier was justified in asserting the identical
relation of the etiology, the close relationship and overla])ping in the
symptomatology and pathology, and that he was right when he destined
them one day or other to be grouped in a single pathological entity; for

SVE’UILIS OF THE NERVOUS SYSTEM

47

Ferrier, in liis admirable Lumleian Lectures on tabes dorsalis, says:
“ . . . and here 1 would express in coiieurrence with Fournier, Mott,

and many other iieiiro-pathologists ot the present day, my belief in the
essential pathological identity of tabes and general paralysis. They
are, in my opinion, imuely different aspects of the same polymorphic
disease.’’ lloth are tabetic, or wasting, aifections of tlie sensory proton¬
eurons in the one case and of the cortical neurons in the other. The
essential etiological factor is the same, and the average time elapsing
between the primary infection and the onset ot the degenerative process
corresponds in the two diseases. Fournier remarks that the establish¬
ment of the syphilitic origin of tabes dorsalis, from his experience, would
necessarily end in the application of the doctrine to general paralysis.
In fact, there are so many symptoms in common and so many analogies
of evolution and termination associating these two diseases that it was
quite natural to conclude the etiology ot one from that of the other.

I have endeavoured to show in the Archives ot Neurology, Vols. 1.
iind II., and elsewheie, all the evidence of the etiology of tabes and
general paralysis tends to prove that there is in all proba¬
bility one essential cause, syphilis, acquiri'd or congenital, and
that there are a number of contribuiing factors, any one of
which by itself or even in combination with others, c.^., sexual excess,
mental stress, heiedity, injury, alcohol, is not capable of producing the
disease. The fact that congenital syphilis leads both to tabes and general
paralysis at so early a period of life as to exclude most of the contribu¬
tory factors exc(*pt heredity, is an argument in favour of syphilis being
the essential cause, iloreover, males and females are affected with
juvenile optic tabes, tabes and general paralysis, in equal numbers. Thus,
of 500 general paralytics that have died and been examined post mvrUm
at Claybury, then? weie 5 males and 5 females who suffered with juvenile
genei'al paralysis; that is, 2 per cent, of the total. I may here remark that
this condition was first described by Ur. Clouston. The study of heredo-
syphilis in relation to these parasyphilitic affections is especially convin¬
cing as to the essential cause of tabes and general paralysis being syphilis.
This has been brought home to me in a very convincing manner in the
large number of cases in which I have studied the family histories. I
will cite a few examples: A young man was admitted to Claybury
suffering with what w(ue termed epileptic fits, the seizures did not cease,
and he died; externally there was nothing on bis body to show that he
had congenital syphilis; his liver, however, show(*d typical signs of
congenital syphilis, and the brain was typical of general paralysis. A
brother in Caterham Asylum piesentod the facies of a typical congenital
syphilitic. I ascertained that the father died of general paralysis, and the

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mother, when I interviewed her, was in the early stage of dementia.
I was asked to see recently at Hanwell a young girl who, blind from
optic atrophy, had later become demented. I was informed there were
no signs of syphilis on the body, and she was one of a large grown-up
family. Fortunately the mother was there at the time. I therefore had
the opportunity of interrogating her. I found it was quite correct that
she was one of a large family, but I also ascertained that, prior to the
birth of this child, there had been several miscarriages and still-born
children, that this child had sulfered with snuffles and a rash, that she
l)ad taken it to the hospital, and grey powders had been given. When
the rash disappeared, she ceased to attend further. As so often happens
in these cases, the mother had not apparently suft'ered, and showed no
signs of syphilis. Another example I may mention : A juvenile para¬
lytic boy was admitted to Bexley and died there; recently his brother
has been admitted with commencing signs of the disease. The former
had Hutchinson teeth, but no history of syphilis could be nbiained from
the father. This man died in Guy’s Hospital. I wrote to the registrar,
and I received tlie information that he had had syphilis. Perhaps the
most convincing case is the following one, which died in Claybury about
a year ago: A boy was admitted with dementia, contraction of all four
limbs, and epileptic seizures; dying not long after admission, the post-
modem examination revealed very advanced general paralysis. There
were no signs on the body, and the boy, up to twelve years of age, was
bright and intelligent; then mental symptoms set in and steadily pro¬
gressed. A history from the father showed that five years before mar¬
riage he had contracted syphilis, which, in spite of long treatment by
ail eminent physician, had not been cured, for the first child died within
48 hours of birth, the second within 24 hours, the third suffered with
late interstitial keratitis, and later nerve-deafness; then came the
patient, and afterwards healthy children. I could multiply these in¬
stances, for, altogether, I have notes of some GO consecutive cases, and
in the great majority (over 80 per cent.) there are indubitable signs, or
an unquestionable history, as in the above cases, pointing to hereditary
syphilis. I have found no case in which I could cedarnhj exclude
syphilis. Particularly common is optic atrophy, which takes these
children to the blind school, and there they develop fits or signs of mental
deterioration, and are next sent to the asylum.

The cases of tabes occurring in heredo-syphilis are not nearly so
numerous as the cases of general paralysis; the ataxy is usually not
very marked, optic atrophy is very common, and tabo-paralysis is met
with often associated with optic atrophy; optic atrophy occurs also pretty
frequently in the paralytic dementia of congenital syphilis. I have seen

SYPHILIS OF THE NERVOX’S SYSTEM

49

two brothers so affected, and die after developing the sigus of progressive
dementia. The period of time elapsing between the evolution of tabes
and general paralysis and the acquired infection varies considerably;
it may be from 3 to 31 years; but the average is 8 to 15 years. The
life of the neurons has been reduced, and the time that will elapse
between infection and the onset of decay depends upon the intensity of
the virus and the inborn resistance of the nervous system, together witli
other supplemental factors causing stress. In these hereditary cases it
is surprising how frequently we find one of the parents, and occasionally
both, suffering from paralysis or tabes; this implies an inborn tendency
to this degenerative condition. Xow it may be asked if twenty-five
years, or even more, can elapse in an adult between the acquirement of
syphilis and the onset of the symptoms of parasyphilis, why should not
the same long period occur occasionally in congenital syphilitic cases,
so that instead of the first symptoms commencing at puberty they are
not manifest till adolescence, or even considerably later. Nonne relates
a case of a workman, aged 32, who had suffered for two years with
lightning pains, and had never been infected with syphilis or addicted
to drink, and who presented all the typical signs of ataxy. He had been
treated in the hospital for severe hereditary syphilis. I have occasionally
observed similar cases of general j^aralysis, e.q .: a man aged 28 died
recently in one of the London County Asylums of very advanced general
paralysis. The disease was first manifested at the age of 18, when he
had a fit. His character was strange; he married, had one child born
dead, and afterw ards his w ife left him. He had no signs of syphilis on his
body, but I found that his father had died eight years previously in
Clay bury Asylum. In my Crooniaii Lectures upon the “ Degeneration
of the Neuron I remarked that it is very probable that some of the
cases occurring in adults in w hich sypliilis can with certainty be ex¬
cluded, may still owe the disease to an inherited syphilitic taint. It is
not even necessary, as quite one-half of the juvenile cases show, that
they should exhibit any external signs of co-ngenital syphilis, for many
of the juvenile cases wdiich I collected w ere proved beyond doubt to be
born of syphilitic parents, although manifesting themselves no external
signs of syphilis, whereas brothers and sisters exhibited very definite
signs. A case of general paralysis died at Banstead Asylum which had
previously been under the care of Dr. Percy Smith at Bethlehem Hos¬
pital. This woman had characteristic signs of congenital syphilis, but
she did not manifest symptoms of ])rogressive dementia till she was 30
years of age. The patient was an unmarried woman, and there was no
reason to believe that she had acquired the disease. Recently Christian
Muller has put forward the same hypothesis to explain those cases in

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which no history of acquired syphilis can be obtained. He describes two
cases of women (virgins) who were the subjects of well-marked signs of
congenital syphilis, and who died of general paralysis at the ages of
42 and 43 years. The symptoms were not noticeable until a year or two
before death.

Dr. Ferrier has in a masterly manner reviewed the evidence whicli
points to syphilis being the essential cause of general paralysis and tabes,
and, in conclusion, I cannot do better than quote him:—“One might
multiply arguments in favour of the causal relation between syphilis and
tabes, but they are unnecessary. For those above related, singly and
collectively, leave, in my opinion, little room for doubt that tabes and
general paralysis are in all cases of syphilitic origin, and that tabes,
per se, is as much a proof of antecedent sypliilis as a gumma of the skin.’'

Although syphilis is the essential cause, yet, as Fournier showed,
tabes and general paralysis are not syphilitic, but an outcome of syphilis,
and the riddle is still unsolved why only about 3 to 5 per cent, of the
persons infected with syphilis should subsequently suffer with one of these
degenerations of the nervous system termed parasypliilitic. But only
10 to 15 per cent, of persons suffering with diphtheria develop post-
diphtheritic paralysis; these are usually cases in which the local infec¬
tive process was mild and often unnoticed; in that respect, like para-
syphilitic affections, which, more often than not, follow mild and even
unrecognised primary infection and secondary symptoms, is it because
the virus is attenuated or modified, and, thereby, has acquired a special
neurotoxic action, or is it because, in a small percentage of individuals,
the cells of the body, especially the cells of the nervo%is system, react to the
virus in a hypersensitive manner? As already indicated, there are facts
which suggest the possibility of a certain form of virus with a neuro-
toxic action. Thus, Babinski remarks thal it seems possible that a
syphilitic virus may sometimes be endowed wdth a particular aptitude for
attacking the nervous system; he reports the case of tw o students who
were infected the same day by the same woman; both died fifteen years
later of general paralysis; these students were, however, related. I have
recently heard of tw^o professional men, not related, who acquired
syphilis about the same time from the same nurse; ten years later they
developed general paralysis. Marie and Bernhard relate the instance of
two men who w-ere infected from the same source, and ten years later
suffered with tabes. Erb narrates an instance of four patients infected
by the same woman, who later became flie subjects of either tabes or
general paralysis, whilst a fifth, w’ho had connection with the woman
but was not infected, did not suffer with any disease later. Probably
the most striking example supporting this theory of a special neuro-

SYPHILIS OF THE NERVOUS SYSTEM

51

toxic virus has been afforded by Brosius, who relates that seven glass-
blowers suffered with chancre of the lip, and out of five who ten years
later came under observation, four suffered with either tabes or general
paralysis. If we accept the fact that a spirochaete is the specific causal
agent of syphilis, it is conceivable tliat there may be varieties of this
organism, as there are of the malarial parasite or trypanosome. Again,
the organism may become attenuated or modified in its passage through
the bodies of certain individuals, or it may be attenuated or modified
by the action of mercury. It may thus happen that the virus may vary
in different cases of infection. This, however, is speculation, and
is not supported, but rather contraindicated so far by experi¬
ments on animals. For, although lower apes have the disease in a mild
form when inoculated from the human being, yet the syphilitic virus of
an infected Macacus Rhesus, when used to infect a chimpanzee, appears
to have lost none of its original virulence; for the chimpanzee suffers
as badly as if it had been infected direct from the human source of the
virus. We are probably, therefore, on more certain ground in attribut¬
ing the variation of the effects which will follow infection, not to the
variation of the virus, but to the reaction of the individual himself; and
we may represent this in the form of an equation: —

, V virus,

bymptom complex <■ = r =

If the virus Y is constant, R resistance must vary. But R is made up
of a number of factors, some of which we can ascertain, but it is gene¬
rally impossible to decompose R into all its constituents. Roughly
speaking, we may say that it is made up of what a man is born with,
what has happened after birth, and what 'will happen in the future to
resist the reaction of the specific virus, which in the majority of instances
is of life-long duration. Most authorities agree that with the widespread
syphilisation of a race for many generations, the disease tends to assume
a milder form; the effects of the disease are not so severe, and a wide¬
spread tendency to an inherited immunity has been brought about. The
conversion of a rural into an urban population has done mucli towards
racial syphilisation and to the diffusion of a tendency to inherited
immunity, and the begetting thus of a mild form of disease. But,
whereas there are fewer cases of severe syphilis than formerly, there are
more cases of tabes and general paralysis. The interesting description
given by Col. Lamb of the syphilisation of the natives of TTganda shows
how severely a race previously free from this disease suffers from
malignant skin, bone, and visceral disease. He also points out that
tabes is very rarely seen. If we consider some facts concerning coii-
genital syphilis, we must come fo the conclusion that immunity is pos-

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52

sible; how, otherwise, can we explain the law of Profela, viz., the non-
syphilitic child of a syphilitic mother does not acijuire sypliilis from the
syphilised mother who suckles it? Again the cliild may be syphilitic,
and the mother shows no signs of syphilis, the mother does not acquire
syphilis by suckling that syphilitic child, whereas a wet nurse does. In
the former case the foetus has acquired some antitoxin or something
from the maternal blood, which has stimulated its own tissues to react
against the virus; in the latter (Colles’ Law) the mother has derived
from the blood of the syphilised child an antitoxin or something (not the
living contagium) which Has stimulated her tissues to react against the
virus so effectively that she cannot be infected. There is no reason to
suppose that the germ cells do not participate in this reaction, seeing
that every cell in the body is subjected to the sensitising influence of
the chemical products of the virus by means of the blood and lymph.
The experiments of Ehrlich have been quoted by Neisser as opposing the
view of inherited immunity; on the other hand, Konradi’s recent experi¬
ments on lyssa support it. The histories I obtained in a large number
of cases of juvenile general paralysis and cases of congenital syphilitic
nervous disease revealed the fact that the mother very frequently had
miscarriages, abortions, and typically syphilitic children, without her¬
self suffering at all, or presenting any signs of syphilis. In two
instances the mother died of general paralysis ; in a considerable num¬
ber of instances the father died of this disease. As a general rule, the
result of successive conceptions is as follows: miscarriages, abortions,
dead children, children dying in infancy—often of meningitis or hydro¬
cephalus, children who later in life suffer with nervous affections, e.g.^
nerve deafness, paralytic dementia, optic atrophy, and tabes; and,
finally, healthy children. Such a chain of circumstances would un¬
doubtedly indicate that either the virus w^as becoming attenuated or
the resistance to its action was increased. In any case, we have reason
to suppose that the children who were born with a syphilitic rash would
be immune to reinfection, also those who afterwards suffered with para-
syphilis ; Kraff't Ebing’s observation supports this premise. It is pro¬
bably a question of the degree of immunity to reinfection that would
obtain in the presumably healthy children that followed the diseased ones.
But such a chain of events does not always occur, for sometimes children
are born with signs of heredo-syphilis after the birth of several
healthy children, also parasyphilitic children may be born after
the birth of several healthy children. This may be explained by the
fact that the specific virus has become active again in the mother,
which inference is negatived in most instances by the fact that she her¬
self may say that she has been in good health and no signs of the disease

SYPHILIS OF THE NEllVoES SYSTEM

53

call be discovered in her. Another explanation olters itself, and it is that
the specific virus may have attacked one ovum and spared another.
Levaditi has seen the spirochaete within an ovum, ^o two individuals,
even of tlie same family, are born alike, because the germ-plasm out of
which they were formed may be similar, but is not the same; one
inherits ancestral tendencies which the other does not; and it may hap¬
pen, therefore, that a child born later than the healthy children possesses
less inborn resistance to the action of the virus; consequently, manifests
congenital 8}q)hilis or, later, parasyphilis. How can we explain this
process of decay of particular groups, systems, and communities of
neurons? Why should we have optic atrophy in one individual, atrophy
of the spinal portion of the sensory protoneurons in another, decay and
atrophy of the cortical neurons in a third, and, in many instances, a
decay and atrophy of the whole neiwous system? We cannot suppose
that it is caused by the random metastasis of the syphilitic organism in
the membranes, or coats of the blood vessels, conveyed by the lymph or
blood stream, as is probably tlie case in the true syphilitic lesions of the
brain and spinal cord. Everything points against this, for, although
parasyphilitic affections present the most varied signs and symptoms,
there is one sign usually present w^hich is, for all practical purposes,
only met with in parasyphilis, viz., the Argyll-Robertson pupil. No
coarse random lesion will explain the constancy of this phenomenon;
moreover, this condition, although a sign of syphilitic infection, does
not occur in true syphilitic brain disease. Spirochaetes have never been
found in the cerebrospinal fluid or antigens. Antibodies are found pro¬
portional to the extent of neuronic decay in tabes and general paralysis.

I think all the facts are against the views of Lesser, Bose, and others
that these late manifestations of degeneration of the nervous system may
be regarded as quaternary syphilis, a very late effect of the virus com-
j)arable with syphilitic orchitis, glossitis, and other sclerous lesions.
According to this view, we should be compelled to consider the meningeal
and perivascular infiltrations and tlie glia cell proliferation as the cause
of the degeneration. But there are many reasons wdiy we cannot accept
this hypothesis. The view I take of the process is that parasyphilitic
disease of the nervous system depends upon two factors, intrinsic,
innate, and extrinsic, acquired—the soil and the seed; the vital re-

V

sistance and the specificity of the virus,

K

All those conditions which may be inherited or acquired, and which
tend to active metabolism of systems, communities, and groups of
neurons functionally correlated, owing to those conditions of stress
causing in one individual spinal neurasthenia, in another cerebral

54

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ueurastlienia, will, in cuujunction with the ellect ol the syphilitic poison
on the lipoids, cause the nerve-cells to exercise an abnormal metabolic
activity.

Ehrlich points out that we cannot suppose that the cells of the body
possess, per se, an executive defensive capacity to neutralise the noxious
effects of all forms of organisms, and his work on haemolysins shows that
the hsBmolysin for the corpuscles of a particular animal only occurs after
incorporation of the molecules of those corpuscles. But we may suppose
that there is an inherent aptitude for the cells of the body of certain
individuals to adapt themselves readily to defence against the action of
the syphilitic virus In a race that has been widely syphilised for genera¬
tions; consequently, a larger number will have a mild form of the
disease. Cases of tabes and general paralysis occasionally arise within
three years of the primary sore; possibly tliis may be due to an inherent
hypersensibility to react to the poison. Dr. Byrom Bramwell has recorded
a remarkable case of tabes which came on ten months after infection;
it would be interesiing to investigate the family history and past personal
history of these cases to ascertain whether or not it was a second infection.

The nerve-cells are perpetual elements incapable of regeneration,
highly differentiated, and complex in structure and function; their
centre of nutrition is the nucleus, and when decay sets in, the regressive
process attacks first the fine twigs and branches of the tree, the dendrites
and dendrons, and the rootlets; in fact, the process is an inversion of its
growth and development. But what should cause this premature decay
and lack of durability, for the specific energy of the whole of tlu' neurons
in the healthy body is sufficient to last until the vital spark dies out?
We know the more prolonged duration of inf activity of the syphilitic virus
as compared with other contagious diseases, also that one attack of syphilis
confers immunity during the rest of the individual’s life; moreover, the
experiments of Kraft't-Ebing are important to remember in this respect.
The nerve-elements being perpetual and having acquired a habit of in¬
creased metabolic activity, will continue it during life, and will contri¬
bute to the excess of lipoids in the blood. When there is no longer meta¬
bolic equilibrium, and decay sets in, these lipoid complexes are
thrown off in increasing numbers {vide p. 37); this seems probable
from the fact that in general paralysis and tabes the quantities increase
w’ith the progress of the decay. The process of decay will manifest itself
in the earliest stages by an increased irritability and functional activity
of the nervous structures, often manifesting itself in a hypercesthesia
seamalisy emotional exaltation, and, not infrequently, in striking intel¬
lectual activity, followed in each case by exhaustion and loss of function.
In my second lecture I referred to the fact that the lipoids may be the

SVrillLlS OF THE NEKVOUS SYSTEM

55

products of nuclear activity and the highly phosphorised nuclein may be
really the source of vital action. We can, therefore, understand how
detrimental a hypersesthesia sexualis is to the vitality of the body.

The uselessness of antisyphilitic remedies is thus easily accounted
for; indeed, they are generally positively injurious in true tabes and
general paralysis because they lower the vital energy of a system which
has over-immunised itself against the syphilitic virus. The only hope of
doing any good is by an early diagnosis of the disease and suppression of
all those exciting causes which use up the nervous energy and tend to
overturn the normal metabolic equilibrium of the nervous structures.
Other factors come in determining the location of the degeneration, and
although microbial infections and microbial toxaemias are not directly
responsible for these parasyphilitic atfections, yet they may be an excit¬
ing agent in the onset of the disease, to the aggravation of the symptoms,
to the acceleration of the progress of neural decay and the fatal
termination.

I have often observed when influenza, dysentery, or pneumonia were
prevalent in the asylums a number of general paralytics died after a
succession of epileptiform or apoplectiform seizures, and I have found,
po$t viortem, that they were suffering from one of these morbid infec¬
tions. It is a common thing to find on tJie post-mortem table patches of
broncho-pneumonia and recent active tuberculosis, the appearances of
which would accord with clinical notes in the case-book reporting the
occurrence of seizures ; and, if the brain be examined microscopically, it
is quite easy to prove that these fits correspond with acute degenerative
changes, doubtless caused partially by congestive stasis and partially by
a toxic condition of the blood exciting and accelerating the process of
neural decay. Bacterial invasion, saondanj or terminal, of the organs of
the body of a non-specijic nature, therefore, may accelerate the morbid
process of decay or bring about a fatal termination.

In conclusion I wish to express my obligations to the President and
Fellows of the College for their kind attention, as I am not unmindful of
the distinguished lecturers who have preceded me; I feel that I have
dealt imperfectly with a very difficult subject still in its infancy, but of
the greatest importance to medical science and practice, and I can only
hope that the words of the old ])hilosopher, Lucretius, may come true,
that one thing after another will grow clear, and dark night will not rob
you of the road, to keep you from surveying the utmost things of nature ;
in such wise things will light the torch for other things.’’

AKCH LVKS

5()

inHLIOliKAPHV.

Lkctuke I.

Mkt( iiNJKOFi-'. Microbiology, vol. 1, System of 8y])iiilis, Oxford I niverBity Press.
Hoffmann. Die GCtiologie der Syphilis, Berlin, 1906.

Neisser. Die Kxperimentelle Syphilisforsohung, Berlin, l9Ub.

Levadjti et \ama\ouciii, L’orientation de la Syphilis, Coinpt. rend, de la Societe

de Biologie, 1908, vol. Ixiv.

Annales de I’lnstitut Pasteur, Tome xxii., Xr. 10, Oct. OH.

Bertarhlli. Transmission de la Syphilis a la cormh- dn lapin, liirisfn (V[(jipne,
1906, vol. xvii. et xviii.

Gautier et Maloizet.. Uevue de yeuroloffie. Sept., /o7, p. 9o9.

Boidin, L., et Wei I.. Mcningite Syphilitiqne secondaire aigne, I*revise Mt dieale ,
No. 85, p. 681, Oct. 19/07.

SriELMEYER. Die Trypanosomenkrankheiten, Fischer, Jnni /08.

Castellani. Dejitselic Med . 1905, Xr. 4d, 171*2.

Linoard. Report on Dourine. ('alcutta Government Printing Office, India.
Rosenheim. The Bio-chemistry of AnimalB and Plants. A comparative study.

Science f^royresa. Nos. 8 and 9, April and July /08.

Munk. I-her lipoide Degenenition. Virchoira Archie, Bd. 194, p. 527.

Levauiti et Yamanoichi. Ihid .

Lecture II.

Wassermann. Ueber die Kntwickelnng der Sero-diagnostik gegeniiber Syphilis,
II. Mitt., Berl. Klin. WochcuHchrift, 1!^07, Xrs. 50 nnd 51.

Citron. Ueber Komplements-Binduiigsversuche, <fec., Dentache Med , Wm ' hem ^ chrift ,
1907, Nr. 29.

Plaut, F. Sero-diagnostik der Syphilis Zentralblatt f. Xervenheilkuude und Psy-
chiatrie. Heft. 8, 1908.

Meiek, G. Die Technik, ZnverUissigkeit nnd Klinische Bedeutnng der Wasser-
inannschen Reaktion auf Syphilis. Berlin Klinit^cJte WochoiHchn/t, 1907,
Nr. 57.

Levaditi et Yamanouchi. Le Sero-diagnostik de la Sypliilis. Societe do Biol.,

Comptes-rendus, T. Ixxii., No. do, p. 240.

[dent. Sero-reaction de la Syphilis et de la Paralj’sie generale,

idem, T. Ixiv., No. 1, /08.

Idetn . T. Ixiv., No. 8. p. 949.

Idem . La rt'action de la dcH'iation du complement dans la maladie

dll .soimneil. BnlleLin de la Soc. de Pathol, exotiijue,
4'ome I., No. 1.

Sachs A Roxdom. Beitriigc ziir Theorie und Praxis der Wassermanscheii Syjihilis
Reaktion. Zeitschrift fiir Iniinunitatsforschung und Experiinentelle Therapie.
Dec. 21/08.

Bruck, C., Stern, M. Die Wassermannsche. A. Neisser. Briicksche Reaktion bei
Syphilis. DtmiHrhe Med. \\\n‘henschrift, 1908, Xrs. lO—12.

Fornet a ScHEREsn km sk V. Sero-diagnost ik hei Lm‘s, Tabes, und Pa»*alyse dnrch
specitische Xiederscldage. Mhue lener Mcil. W’w heusrlir ff, 1907, Xr. 90.

SYrillLlS OF THE iNEKVOl S SYSTEM

57

Klausner, E. Ueber eine Methode der Seruni-diagiiostik bei Lues. Wien. Klin.
Wochenschriftj 1908, Nr. 11.

Fritz & Keen. Ueber deii Wert der Serum-reaktiou bei Syphilis nach Forges.
Meier uud Klausner. Wien. Klin. Woehensehrift, 1908, Nr. 1*2.

. Noouchi. The Relation of Protein, Lipoids and Salts to the Wassermann Reaction.
The Journal of Experimental Medicine, vol. xi., No. 1, 1909.

Lecture III.

Blumentiial. Neurol. (Jentralhlati, 1908, p. 1000.

Fournier. Les affections Parasyphilitiques.

Max Nonne. Syphilis des Nerven-systems.

Hoffmann. Ibid.

Neisser. Ibid.

Roux & Metchnikoff. Metchnikoff ibid.

Krapft-Ebing. Discussion upon General Paralysis. Internat. Congress, Moscow.
Ref. Neurol. Centralblatt, 1897.

S( huster. Hat die Hg. Behandlung der Syphilis Einfluss auf das Zustandekommen
Metas^’philitischer Nervenkrankheiten. Deutsche Med. Wochenschrift,
Dec. 12/07.

Virchow. Ueber die Natur constitutionell Syphilitischer Affectionen. Virchovys
Archiv.f iir Path. Anal. Bd. xv., 1858.

ScHULGOWSKY. Blutunt^rsuchungen mittelst de.s Hiematometers von Hayem. Si,
Petersburg Med. Woehenschrift. 1878.

Laache. Die Ana3mie, 1883.

Martin & Hillier. Ref. Max Nonne, ibid.

Letzius. Max Nonne, ibid.

Mott. Archives of Neurology, vols. i., ii., iii.

Croonian Lectures “The Degeneration of the Neuron,” Jjaucet, 1!><H).
Ferrier. Tal)es Dorsalis. The Lumleian Lectures, 1900.

Muller, Christian. Miinehener Med. Wochensclrift. Sept. /08.

Lamb, Col. Article: Syphilis in Uganda. Lanret, /08.

Konradi. 1st die erworbene Immunitiit vererbar? Centralblatt far Baki. Bd. xlvi.,
Nrs. 1 und 2.

Krapft-Ebing. Ibid.

Lesser. Zur Etiologie und Pathologie des Tabes, speciell ihr Verhaltnis ziir
Syphilis, Berlin Klin. Wochetischrift, /04, Nr. 4.

Bo.se. Les Maladies bryocytiques. Uetitralblatt f. Bakl. Abtriig, Bd. xlii.. Heft. 5.
Lesser. Ref. Bose.

Ehrlich. Croonian Ijectures. Proceedings of the Royal Society, /04.

Bramwell. An analysis of 203 cases of Tabes. British Medical Journal. ,08.

Ibid. Lancet, Nov. 14 08. Report of Meeting of Edinburgli. Medico-Cliir.
Society.

58

ARCHIVKS

A CASE OE GUMMATOUS MEMAGITIS IN A CONGENITAL

SYPHILITIC.

F. vv. myn \ m.d., f.k.8., f.k.c.i*.

E. M. A. Eeniale, aged IG years. Admitted tu Claybury Asylum
80/8/05, died 8/7/00. Previously a maid servant, and had dune general
work for her father for the last two or three years.

Histoty obtained from [t at lent'$ Eatlier, interviewed by me,

gave the following history. His occupation had always been that ol
a coachman. JSo insanity on his or the mother’s side. The mother
of the deceaiied girl diet! when the girl was six months old. He
married at the age of 20, his wife being a single woman before marriage,
and a servant. I could obtain no history of venereal disease or excessive
indulgence. in alcohol. There were five children born alive, and three
miscarriages. The first three pregnancies resulted in miscarriages, and
then followed five children born alive, of whom the deceased girl was the
last to be born. The rest of the children were all healthy and alive, with
the exception of one little boy, w ho died at the age of nine years. I could
obtain no information regarding the cause of tbe mother’s death, except
that she had dropsy.

The deceased girl was always delicate from birth. She had
snuffles and convulsions, and was treated with grey powder. No
history of rash. She w^as intelligent, quiet, and always reading, and
nothing unusual was noticed until 18 months ago, wlien she became much
quieter and forgetful, and would say funny things to her step-mother,
and laugh if rebuked. About one year ago she suddenly left her father
for no apparent reason, and went to her sister, with whom she stayed.
Here she started singing and dancing, and became excitable; a doctor
w’as sent for, she w^as removed to the infirmary, and thence to Claybury
Asylum. The deceased girl never had any fits and was not of a worry¬
ing disposition. She fed and lived well. She was intelligent at school,
and passed the sixth standard. The father married a second time, but at
the present time there have been no children or miscarriages.

The patient, on admission to the Asylum, was considered to be suf¬
fering from congenital imbecility and mania. The case book notes state
that she was excited, garrulous, and incoherent, singing snatches of comic
songs and hymns. She appeared to be weak-minded, but her ability to

GUMMATOUS MENINGITIS

59

reiueulher songs aiul their words was wondeifiil. It was observed that slie
was undersized, poorly nourished, and had Hutchinson teeth. {Vidt
Fig. III.)' The knee-jerks were piTrs<*nt, and there was slight internal
strabismus of the right eye. The oHicial notes from this time onwards
are of no interest till the day before her death, when she is said to have had
a seizure of the right side of her body and the left side of her face, followed
by coma with stertorous breathing. There was an internal squint of the
right eye. I obtained the following further information from the nurse:
she was childish in her voice, speech, and actions, and amused herself
with dolls and jiicture books, and made no attempt to read or write.
(There must, therefore, have been considerable dementia, for I ascer¬
tained from the father that she had passed the sixth standard at school).
She was faulty in her habits, but was afterwards sorry when corrected.

Fig. III.

Teeth of tlie patient. Phot<>gra])h taken after death.

She was amiable, obedient, and affectionate, and a favourite with the
nurses and patients. She had no delusions or hallucinations, and until
the day before her death never liad a fit. She would occasionally make
mistakes as regards personal identification, and would call the nurse,
mother. She never menstruated while in the Asylum. She took her
food and enjoyed it. The songs she sang and her conversation did not
lead the nurses to suppose that she had been immoral.

For three months before she died, she had stiffness and rigidity of the
neck, holding her hand in such a manner that the doctor examined her
several times for caries of the spine. She had then become helpless and
drowsy, taking nourishment badly, and no longer singing her comic
songs.

StnnnK/ri/ af autopsy .—The brain weighed 1,125 grammes. It was
.soft and cpdematous. There was excess of subdural fluid and the convolu-

AIIUIIIVLS

(iU

tiulis were llutteued. Tlie convolutiuual pattern was good, and of average
complexity; the Sylvian angle was also good. The wTiole of the base of
the bruin was covered with a greyish yellow deposit or membrane in places
semi-fluid, but otherwise of fairly firm consistency and tough.
On stripping this off, the brain substance beneath was left pitted,
a similar condition was found on the orbital surface of the frontal
lobes, and the mesial aspect whereby these were adherent. A
greenish-yellow gelatinous semi-fluid material covered the anterior
perforated spots and spread up the Sylvian Assures on both sides.
On the under surface of the cerebellum there was a small maroon-
coloured swelling. The vessels at the base of the brain and their
extensions into the fissure were much thickened, and had a dirty
greyish-yellow appearance, like dirty wash-leather. In places the
lumen of the arteries of the circle of Willis was either partially or com¬
pletely obliterated [vide Fig. 3, Plate IV.). The middle ear and nose were
carefully examined to see it there was any cause for this meningitis, but
without success. Cultures were made, and no pyogenic organisms were
found. The ependyma of the fourth ventricle showed marked granula¬
tions.

The same deposit observed at the base of the brain was found extend¬
ing down the spinal cord lying in the subarachnoid space. This greyish-
yellow gelatinous exudation, after hardening in formalin, formed a firm
tissue, wTiich was especially thick in the region of the cervical enlarge¬
ment, being there 3 or 4 mm. in thickness. The vessels and large arteries
of the central nervous system appeared like solid cords or threads of
varying thickness, they did not collapse on pressure. Wlien cut through,
the sections showed markedly thickened walls, and the lumen in some
instances was obliterated.

The liver was denser than natural, otherwise there was no naked-eye
change. The aorta showed slight atheroma. There was no evidence of
tubercle, the lungs only exhibited bronchitis, congestion, and oedema.

Sections of the cortex cerebri, cerebellum, pons, medulla, optic nerve,
arteries of the circle of Willis, and the spinal cord at various levels were
made and stained by haematoxylin and eosin, and polychrome methylene
blue and eosin.

Histological Changes.

Cortex cerebri. —The meninges were infiltrated with lymphocytes and
])lasma cells, the pial vessels were markedly affected and the lumen
diminished by this infiltration; in places where the meningitis was most
marked, the infiltration was extending along the pial sheaths into the
.substance of the brain; but, as a rule, there was little or no change in
the vessels in the cortical substance. The perivascular infiltration, then.

GUMMATOUS MENINGITIS

61

was clearly an extension from the meninges. There was little or no sub-
pial felting or glia proliferation, and the columns of Meynert were not
distorted in sections of the middle of the first frontal convolution. In the
ascending frontal, however, there was much more evidence of affection
of the vessels of the cortical grey matter; in fact, there w as a very definite
patchy encephalitis, and a very definite and abundant formative proli¬
feration of the connective tissue cell elements of the small vessels and pial
sheaths, so as to diminish or completely obliterate the lumen of the
vessel. It seems that the process was an extension from the meninges,
for it w^as much more marked on the superficial vessels.

In a section stained by haemotoxylin and eosin of such a vessel ex¬
amined with an oil immersion lens, the perivascular sheath—and even
the lumen of the vessel—w’as filled wdth branching connective tissue-cells,
the body and processes of w hich stained pink; lying in these pink-stained
cells were purple, round, oval, and irregular nuclei in little clusters, the
result of rapid division. The appearance was exactly the same as those
observed in chronic trypanosome affections. The neuroglia cells appeared
to be undergoing an active i)ro]iferation in the superficial layers of the
cortex. In the cortical exudation and infiltration there were numerous
plasma cells, and in places the neoplastic cell formation was undergoing
a granulo-aqueous degeneration; plasmolysis and nucleolysis were very
evident. Hei’e could bo seen the cells taking the eosin stain diffusely;
they had a fainter and less brilliant staining reaction, and large numbers
could be seen containing granules of chromatin of varying size. Jfo
micro-organisms w’ere seen. The vascular changes indicating subacute
meningo-encephalitis w^ere very suggestive of acute general paresis.

7'he cerebellum show^ed the same periarteritis and endarteritis, and in
the place w^here there was a maroon-coloured swelling, microscopic ex¬
amination showed a hsemorrhage of some standing. All the vessels in
the neighbourhood were profoundly affected in the manner described
above and figured, Plate II., Figs. 4 and 5. The meningeal and peri¬
vascular and vascular neoplastic formation extended all the way down the
spinal cord; it is shown in the accompanying photomicri^raphs. Figs. 1
and 2, Plate I\ . Xo tubercle bacilli were discovered by appropriate
methods of staining, no pyogenic organisms were obtained by culture,
and no organisms were obseiwed in the sections stained by polychrome-
eosin to account for this meningo-encephalitis and meningo-myelitis.
The infiltration around the optic chiasma was especiallv marked. It
is difficult to understand why the child’s sight was not more seriously
affected, seeing that the perivascular infiltration had extended
some distance into the chiasma. Very probably it was, but the
cliild in the later days of its illness was in a too demented and stupid

62

ARCHIVES

state for it to be discovered. Curiously enough, although the child had
a stiff neck and a squint, apparently no attempt was made to examine
the fundus.

All the arteries of the circle of Willis showed profound j)eriarteritis and
obliterative endarteritis {^nde Fig. d, Plate IV.). The meningeal and
perivascular neoplastic infiltration w’as universal; it corresponded entirely
in its histological character with a gummatous meningo-encephalitis.
Polymorpho-nuclears were conspicuous by their absence ; the neoplastic
formation consist of proliferated, branched, and spindle-shaped connec¬
tive tissue-cells, and round or oval cells in which there w’as a distinct cyto¬
plasm of varying thickness forming all grades between lymphocytes and
plasma cells ; there are also large macrophages. Large numbers of the
cells were undergoing a granulo-aqueous degeneration, but the course of
the disease w'as too intense and short to allow of abvsorption of the products
of nucleolysis and plasmolysis and leave the connective tissue-cells to go
on to the formation of fibrous tissue. Exactly the same sections of the
cortex stained to display fibres showed some degeneration and destruction
of the tangential system, but there was no marked evidence of sub-pial
glia proliferation, nor was there any sub-pial felting ; the perivascular in¬
filtration clearly was an extension from the pia-arachnoid along the pial
sheaths. Considering the universal vasctilar change and perivascular
infiltration, it was astonishing how little destruction of cells and fibres
had occurred. This can be correlated with the fact that there was com¬
paratively little naked-eye wasting of the cortex. The cells in the super¬
ficial layers of the cortex are undoubtedly more affected than the deeper
layers, and this is most marked in those patches of cortex where the
chronic inflammatory process has extended most along the pial sheaths.

PLATK IV.

Fig. 1.

Section of lumbo-sacnil Bpinal cor<l showing chronic
gummatous leptomeningitis extending along the small
vessels into the sub.mance of the spinal cord. Mag. *200.

Fig. 3.

Section of various basal arteries showing obliterative arteritis.
Mag. 15.

Fig. 2 .

Section of the membranes showing the character
of the formative cell h> i)erplasia, /. lymphoi'yte.s/;.
platmia cells. Mag. TOO.

Fig. 4.

icction of the endarterium, showinK lynnphocyte* and
)lasma cells undergoing granular degeneration. Mag. -hO.

Fnrr p. <»2.

63

A CASE OP LOCALIZED SYPHILITIC PACHYMENINGITIS
CEREBRI WITH SPEECH AFFECTION.

By F. W. MOTW M.D., F.H.S., F.H.C.P.

A. G. Aged 44 years. Adiuilied to Hauwell Id/dyUS for epilepsy,
loss of memory, and aphasia, from wJiieli she for a time improved.
The history obtained showed that her husband had had syphilis
eight years ago. She had been married over six years to him. She was
his second wife, and has had no children or miscarriages by him. There
were several papery scars on the body, and there was some slight glan¬
dular enlargement, but the signs of syphilis were not distinctive. Still,
the symptoms pointed strongly to syphilis, and in my judgment it was
desirable at once to push anti-syphilitic treatment with mercurial inunc¬
tion after attending to a bad condition of pyorrhoea alveolaris and
stomatitis.

I saw this patient on 17/5/08, my attention being called to the case
by Dr. Daniel, under whose care she was. I found paresis of the right
lower half of the face, with marked deviation of the tongue to the right.
She was unable to close the right eye independently of the left, although
she could wdnk and close the left eye independently perfectly well when
asked to do so. There w-as some weakness of the right hand as compared
w’ith the left, and the deep reflexes were increased. She tried to talk,
but her speech was hardly intelligible, although she understood all that
was said to her, as was show n by her obedience to all commands and the
endeavours she made to reply to questions; it appeared that her condi¬
tion of speech defect might be due to dysarthria rather than aphasia,
for her utterances w^ere intended apparently to represent her silent
thoughts. She is unable to read or w rite, and, tlierefore, could not be tested
in this respect. I saw her in several fits. The fits come on quite suddenly ;
when asked w hether slie knov s wdien a fit is coming on, she points to her
tongue and lower half of the right side of the face. I asked her if she
felt a numbness there, she responded in the affirmative. Slie does not
lose consciousness, as she will obey commands w hile the fit is proceeding.
The fit starts in a spasm of the mmscles of the lower part of the right side
of the face and jaw, this spreads up and down to the right orbicularis
palpebrarum and corrugator suporcilii, which are thrown into spasm, also
the platysina of the neck. I thought there was some deviation of the eves

f)4

ARCH IVES

to the right on one occasion, but she was able to look to the left when told
to do so w’hile the fit was proceeding. The spasm of the orbicularis pal¬
pebrarum spread to the opposite left eye and the eyeballs rolled upwards;
it did not spread to the opposite lower face, nor did it spread to the arm.
She has never complained of headache, but there was a tender spot on
pressure just above the attachment of the left ear to the skull. There
was no optic neuritis and no vomiting. The diagnosis I made was gum¬
matous pachymeningitis over the region of the left ascending frontal and
parietal convolutions at their lower extremity, involving especially the
tongue area, also probably the pars basilaris of the third frontal.

Subsequent Notes by Dr. Daniel.

May 17th, 1908.—The notes state that the fits continue on an average
about 50 a day. One fit lasted about 80 minutes (probably it was a
series fused together), but it is interesting to obseiwe that she remained for
1^ hours unable to sjyeak at all.

May 20th, 1908.—She has had 50 fits in the night, and they are
occurring every few minutes in the morning. Yesterday she complained
of numbness and pains dow'n the right arm. To-day there is distinct deixia^
tion of the eyes to the right during the tonic stage of the convulsion, and the
fits are occasionally attended by loss of consciousness. She is now being
treated by mercurial inunction tw ice a day.

May 26th.—The notes state that the fits now extend to the right arm,
and various sedatives were given, including hyoscyin l-50th grain,
w^hich, it is stated, has had a marked effect; she has had fewer fits and
is markedly drowsy this morning; the pulse is feeble and rapid.

May 80th.—A difficulty in swallowing has been observed, and there
seems to be an actual paresis. Fits continue practically uncontrollable.

June 1st.—The fits ceased, but patient died June 2nd at 4.35 p.m.

On June 3rd I made the post-mortem> examination.

On removal of the calvarium, a pachymeningitis about the size of a
florin was observed in the region of the tender spot noticed during life
just three-quarters of an inch above the attachment of the left ear. On
opening the dura mater the thickening was very definite. It was about
five times as thick as the normal dura mater. This thickening was uni¬
form, except at the circumference, where it gradually sloped off. It was
red and inflamed both externally, in contact wath the bone, and inter¬
nally, in contact with the pia arachnoid. The bone in contact with the
inflamed dura was roughened, and there was a slight degree of osteitis;
the middle meningeal artery passed through the middle of the patch.
Internally the pia arachnoid was red and inflamed, but there was no
symphysis with the dura mater in this situation. One inch and a quarter

SYPHILITIC PACHYMENINGITIS CEREBRI

65

further back the dura mater was a little thickened (twace the normal)
and adherent to the pia arachnoid, so that on stripping, erosion of the
surface of the brain occurred over an area the size of a florin at the end
of the fissure of Sylvius, involving the posterior end of the first temporal,
the adjacent marginal, and, to a very slight extent, the angular gyrus.

Upon close examination the anterior patch of pachymeningitis showed
several small case^ous nodules about the size of a hempseed; it was found
to be situated exactly over the lower end of the ascending frontal and
tlie adjacent inferior frontal and ascending parietal convolutions. There
can be no doubt that this gummatous pachymeningitis was the cause of
tlie Jacksonian epilepsy; and it could have been removed by operation
with the greatest of ease. At the autopsy no organic disease of other
organs, nor of the brain itself, w’as found; and it was a great pity that
the patient was not sent to a hospital as I recommended, for, in my judg¬
ment, it w^as a most suitable case for surgical treatment. She would
have been transferred at once had tliere not been legal difficulties and
formalities to overcome.

Microscopical Examination .

I. Portions of the following structures were hardened in formalin
and cut after being embedded in paraffin: —

{a) The syphilitic pachymeningitis, the cortex beneath comprising
pars basilaris, ascending frontal and ascending parietal convolutions. A
portion of the corresponding cortex of the right hemisphere w^as taken
for comparison.

(6) Portion of the posterior part of the left first temporal and adjacent
marginal convolution.

(c) The medulla oblongata at the level of the olivary bodies.

(d) The cervical enlargement of the spinal cord.

The sections 10/x in thickness were stained by Nissl, polychrome,
Giemsa, Van Gieson, and Heideiihain eosin methods.

II. Portions of the tissues and {h) were taken after the brain had
been in formalin for 24 hours and prepared by the Cajal method.

Description of Histologic.yl Changes.

The iHuhymeningitis^. —The fibrous bundles of the dura were swollen
and separated by an infiltration of lymphocytes and plasma cells; these
were unequally distributed, in places forming little nodular aggrega¬
tions. Moreover, in some situations these collections of cells had under¬
gone necrobiosis and transformation into a granular mass of detritus
(juite typical of a gumma. The sections showed the middle meningeal
artery in transection, also some of its branches ; the latter showed a

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marked periarteritis, that is the adveiitia, was infiltrated with young
cells; but the main trunk not only showed this condition, but also almost
complete obliteration of the lumen by endarteritis. (Vide Fig. 4.)

The cortex hencath the pachymetiniqitis .—The pia arachnoid showed very
little cell infiltration, and there was next to no extension along the pial
sheaths of the vessels, and this accorded with the fact that there was no
symphysis of the dura to the soft membranes. The superficial layers
of the cortex exhibited a marked proliferative hy])erplasia of the neuro¬
glia cells {x^ide Fig. 5), especially evident in sections stained by all the
methods mentioned when a comparison was made with the corro-

Fl«. 4.

Pliotomicrogniph of the nrnlflle mcniiif,^ciil in giiinnuituii^ paciiyineiiingitis.

Magnification So.

sponding cortex of the right side. [Vide Figs. 1 and 2, Plate V.) I do
not think this glia proliferation could be accounted for by the wasting
of the neural elements, but it was a direct expression of irrita¬
tion caused by the superjacent infiammatory condition of the dura
(possibly toxic chemical substances). There was some d egrets of
atrophy of the tangential fibres, otherwise the fibre systems appeared as
intact in this region of the left hemisphere as in the same region of the
corresponding hemisphere. The columns of Meynert of the pyramidal
layer were intact, the apical processes of the cells were straight, and

SYPHILITIC PACHYMENINGITIS CEREBRI

67

exhibited no cork-screw appeanuices; but it was possible that their ulti¬
mate termination, as well as the terminations of the Betz cells in the
tangential layer were damaged or destroyed; otherwise the outline of
the cells corresponded with the outlines of normal cells. By Nissl stain¬
ing the cells showed large clear nuclei and a marked deficiency of chro-
niophjdlous substance. Tlie tigroid substance was almost absent in the
body of the cells and on the deudrons in sections of the left ascending
frontal. A similar appt^arance was observed in the right ascending
frontal, but it was not nearly so intense; there was more chromophyllous

Fig. 5.

Pliotoinicroj^niph of cortex of left f.icio-linj^iial area stained by C'ajal fibril method ; it shows
remarkably well the neiiroj^lia (;ell hyperplasia and their extensions on to the walls of
the small vessels. .Maj^'^niticalion .‘IdO.

substance, and the cells staine<l less faintly. (TvY/c Figs. 1 and 2, Plate
V.) By the silver method, fibrils could be seen running thnnigh tlie cells,
and there was apparently not veiy much change.

The sections of the cortex at the end of the left Sylvian fissure exhi¬
bited very similar changes, but owing to the adliesion of the pia arach¬
noid to tlie dura, the cortex presented an eroded appearance; apparently
the inflammatory process in this lesion started in the pia arachnoid in¬
stead of within the dura : it was more recent in origin and less extensive.
There was a marked glia proliferation, and the same ciianges in the
layers of cells noted in the other lesion.

Medulla oWrm/7/7/(7.-—Examination of the medulla oblongata showed a

E 2

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iiiarked diminution, and, in some cases, absence of chromatic substance
in the cells of the facial, hypoglossal, and spinal accessory nuclei on
both sides. It was thought that the right nuclei were more aHected than
the left, but it is difficult to be in any way positive about this. There
could be no question that, compared with the appearance of the ^issl
pattern of the cells in the anterior horns of the cervical enlargement,
both the Betz cells of the motor cortex and the cells of the above-
mentioned motor nuclei of the medulla oblongata showed a marked dimi¬
nution of the chromatic substance; although some of the cells of the
anterior horns of the spinal cord were not quite up to normal standard.
From these facts it may be inferred that the cells where the primary
lesion was acting as a cause of excitatory discharge, giving rise to Jack¬
sonian epilepsy, exhibited the most notable signs of exhaustion, as
measured by diminution or absence of chromatic substance. This could
not be due to 'pod-movtem change, because the cells of the anterior horns
of the spinal cord showed a fairly normal Nissl ])attern; nor, for the same
reason, could the changes be due to the administration of drugs to con¬
trol the fits prior to death, and it is permissible to assume that the most
marked absence of Nissl granules observed in the cortex situated beneath
the primary dural lesion may be explained as a result of exhaustion from
discharge of energy in the local epilej)tiform fits produced by the local
irritation. Subsequently the fits spread and became generalised, conse¬
quently the cells of the cortex of tlie right hemisphere showed some
degree of exhaustion.

Association of the synvptoins jjvcse/tfcd during lifc^ with the lesions
ohserved post mortem .—Undoubtedly the dysarthria and the Jacksonian
epilepsy which I observed were in the main due to the pacliymeningitis
involving the lower end of the Rolandic fissure; but was the conjugate
deviation (at that time hardly observable and certainly of later mani¬
festation than the facio-lingual epilepsy) due to this lesion, or to the
leptomeningitis involving the cortex behind the posterior end of the
Sylvian fissure y The conjugate deviation to the right was only begin¬
ning to be manifested on May 17th, but later it became quite definite.
Tn point of time of its initial manifestation it would coincide with the
development of this lesion, although it might be explained by an exten¬
sion of the zone of irritation caused by the anterior lesion, for clinical
observation showed that the facio-lingual spasm was followed by tonic and
clonic spasm of the right arm, at the time the conjugate deviation of the
eyes to the right was noticed. It has been shown by Wilson that there is
an association of pricking of ears and conjugate deviation of eyes. More¬
over, cases have been recorded of conjugate deviation of eyes resulting
from lesions in tin’s temporal region.

SYPHILITfC rAC'IlVMKNIN(ilTIS CEREIiKI

69

DESCRIPTION OF PLATE V.

Pig. 1.—Camera lucida drawing of small i)ortion of left facio-lingual cortex beneath the
pachymeningitis. The superticial molecular layer is shown and the fourth layer ; the
intervening pyramidal layers are not shown. It will be observeii that in comparison with
a similnr portion of the cortex of the right hemisphere there is a marked hyperplasia of
the neuroglia cells. These cells are undergoing active proliferation, the cytoplasm is
markedly increased. There is a large Hciz cell seen in which the Nissl granules are only
very faintly seen, although the outline of the cell is not materially altere<l.

Fig. 2. —Camera lucida drawing of small portion of the nght facio-lingual cortex. The glia
cells are smaller, less numerous, and show but little hyperplasia as compared with those
seen in Fig. II. A large Bet/, cell is shown ; this exhibits a normal appearance, except
perhaps the Nissl granules are not quite so large and distinct as in a normal brain.

Both Figs. I and 2 were drawings of preparations cut in paraffin, and stained with poly¬
chrome eosin. Magnification “>00.

TUBERCULOSIS IN THE LONDON COUNTY ASYLUMS.

U\ F. W. MO'IT. M l)., F.R.S., F.H.C.P.

(’OM’KN'rs.

INTHODl’crnoN. -

Xotilicjitioii — (of Ward I iicitltMicr ot D^’sfMitei’V and
Tuhrrclo .

PAliKS

70-7^5

HF(7Id().\ I.—Inciijkxce ok Ti liKKon.osis in tiik Fun don ('ointv Asvm ms.

{( l ) I \( ll>K\( K A.MONli fiI\IN(i FaTIKM’s.—

IncideiK f at tlu‘.s(‘voral London County Asylums—'riino of Diagnosis
— Associalion with Montiil C’ondition— A}j:o at'riino of I)iaiynosis ... 7d-7t*

( h ) Deaths with Actink ihiniisis in tmh Lom»o\ Coi nty Asvi.tms
KOK Fink ^'eaks (1/1 od

(■oini)arison of Deaths at the sev(*ral fjondon County Asylnnis—

Age at time of death—(.’omparison of the Phthisis death i*ates at
the several age periods for the sr(j/» and lnsniir London inhahitants
—Racial ineidenee of'I’uhereulosis ... 80-89

(r) Incidence of Phthisis amongst Asylmn Oflicials 89-9d

SECTION 11 .— 8 i:m.m\kv ok Statistk s kkkatin(i to Ti aK.io i losis kound
FOST MORTKM AT (’knNMI KV .VsNI.IM FOR TkN VkaUS (1 '9 98 —
dl 8 (ts).

(Annparison of Incideiice among Ceneral Paralyt i(*s and Non-])aralyti(\s
-Cavitation -Length of Residence in A^^ylum — Incidence of
Obsolescent 'rnhercnlosis —ProhaMe Time of hdection—Association
with Mental Condition- lnllnei'ce of Occupation .. ... 94-l0o

SECTION III.-Profiivlaxis..

lOo-lU

SUMMARY . 114-lU)

IXTRODrCTION.

In consequence of a valuable coinniuiiication ii]K)ii llie subject of
tuberculosis in asylums by Dr. Ci'ooksliank, entitled “The Frequency,
Causation, Prevention and Tr(‘atnient of Pulmonary Phthisis in Asylums
for the Insane,” followed by a ])apei communicnted by Dr. Eric France,

Tl llKRCri OSTS 1\ LONDON (’Ol NTV ASYLl’MS

71

tlie M(Mli(*J>-rsyeholopical Associaiion appointed a Coinmittet' to investi¬
gate the matter. The conclusions arrived at were that: —

(1) It is a fact heyoml (question Hud )jhthi»is is p'revalent in oar j/ablic
Asylums to an extent which calh for urgent measures^ and that large numbers of
patients contract phthisis after adm'issicrn into the Asylums, (2) The special
causes for this iiwreased prevalence of phthisis are, in our opinion, overcrotvding,
with co'nseguent imufficiency of hours in the open air ; defects in ventilation and
heating, uncleanly habits and faults in dAetary,

These conclusions were regarded in the main as being sound, but the
statistical tables upon which they were based were thought in some
respects to be unreliable, and consequently a revision was made by
])r. Chapman, whose deductions were as follows: —

(1) Infection is one of the strangest causative elements in the prevalence of
lulferculosis in Asylums. (2) A healthy, dry, and welMrained site is of extreme
importance. (3) The causes of tuheixulosis in Asylums inhere in the Asylums
themselves and not in the character of the patients sent to them, althmujh certain
Asylums jrresent exceptions.

The value of these figures was materially impaired by virtue of the
fact that the majority of tliem w ere not supported by evidence.

The statistics, therefore, depended largely upon the uncontrolled personal
equation of diagnosis. The diagnosis of tuberculosis in the earliest stages
in the sane is, as is well knowm, an extremely difficult matter, and it is
generally admitted by all asylum medical officers that many and varied
difficulties occur in arriving at a diagnosis of early phthisis in the insane.
The patient resists examination or, if in a melancholic or stuporose
state, the breathing is so shallow as to be difficult to hear, and often
the patient cannot be induced either to take a deep breath or to speak.
Again, many patients do not expectorate, and hence no sputum is avail¬
able for examination for tubercle bacilli. For these reasons Dr. Eric
France advocated the use of tuberculin as a means of diagnosis. Doubtless
this w^ould be a useful diagnostic measure, but, unfortunately, the test
makes no distinction between obsolescent or quiescent tubercle and the
active form of the disease, and isolation of all cases that reacted would,
on the infective theory, lead to reinfection of quiescent cases. Moreover,
we are not sure that the injection of tuberculin might not reignite a
quiescent form of the disease. Calmette’s ophthalmic reaction would not
have this objection, but it might, as with tuberculin injection, lead to a
wrong conclusion about the disease. For these reasons, I presume,
neither of these methods have been generally adopted in asylums.

Notification .—The Pathological Sub-Committee of the London County
Council, recognising the benefit that had resulted from the notification

72

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of dysentery and llie importance of the question of tlie prevention of
tuberculosis, instituted, at my suggestion, a system of notmcation of all
cases of tuberculosis in the London County Asylums. ALonthly reports
for the past five years have accordingly been made, affording tiie follow¬
ing information; Age on admission, sex, date of admission, ward, mental
disease, date of discovery of tuberculosis, progress of the case, and
ultimate result; if death, the post-moitem findings. These reports have
been systematically collated by my assistant, Mr. Sydney Mann, and tlie
data and deductions embodied in this communication are drawn from the
statistical evidence thus afforded, together with the information from the
records of the yod-mortem examinations made at Clay bury Asylum by
myself or my assistants during the last ten years. Moreover, during one
year, I personally conducted all the post-moiU m examinations at Colney
Hatch with a view to ascertaining whether the results corresponded with
those at Claybury.

During the last eight years notification of all cases of dysentery and
diarrhoea has been in operation in the London County Asylums, and it is
satisfactoiy to know that the isolation of persons suffering from this
disease has corresponded with a considerable diminution in all the
asylums; it does not now attain to serious epidemics in wards as it did
before this notification was instituted. Moreover, I do not see on the
post-mortem table nearly so many cases of severe and acute dysentery at
Claybury as heretofore. Nor is it a common occurrence as formerly for
nurses, attendants, medical officers and employes in tlie asylum to suffer
with dysentery as the result of an infection which could in many cases
be definitely traced. These facts of themselves show the advantages of a
system of notification, even if such notification only serves to call atten¬
tion to the infectivity of the disease and the prevention of epidemics by
isolation and other prophylactic measures. The Committee felt, there¬
fore, that the same benefit might accrue from the notification of all cases
of tuberculosis with a view to proper prophylactic measures.

Comparison of ward incid< net of dysentery and tuhercle .—Comparison
of the ward incidence of these two diseases shows that in the case of
dysentery there is ward incidence indicative of infection, althcugh seldom
now attaining a serious epidemic form. Before the notification and
isolation of cases of dysentery I have known one ward of an asylum to
have one-third of its patients suffering from the disease, the total number
of cases amounting to many more than were contained in all the remain¬
ing w-ards in the asylum. Moreover, sometimes one asylum will notify
at one period of time more cases than all the other asylums together.
Now" in the case of tubercle, the reports show no such special ward
incidence, and I have systematically asked the superintendents and

TUIJERCLLOSIS JX LO.NDON COUNTY ASYLUMS

7y

medical officers wlietlier tiiey are able to iuiuisb me with auy reliable
evidence pointing to an attendant or nurse acquiring tuberculosis in the
asylums. Dr. Seward of Colney Hutch Asylum is of opinion that two
attendants acquired tuberculosis owing to their being employed in a
particular ward in that institution, and Dr. Jones of Claybury Asylum
considers that some attendants may have acquired tuberculosis after enter¬
ing the service, otherwise the replies have been in the negative {vide
p. DO). This conforms pretty much with the experience of the Vent nor
and Brompton Hospitals, as indeed with that of all sanatoria for con¬
sumption. It might, however, be argued that tuberculosis should nevtr
occur in a nurse or attendant, for all are examined as regards their general
health upon entry of service.* The obvious answer to this is that pro¬
bably more than ‘.jO per cent, ol tlie presumably healthy adult public have
obsolescent tuberculous lesions ; the post-yiiorteni findings at the asylums
show the presence of obsolescent tubercle. Brouardel found that 50 per
cent, of the bodies of persons who had met with violent deaths and had
been taken to the Morgue in Paris presented tuberculous lesions. Dr.
Harris, of the Manchester Royal Infirmary, found in 39 per cent, of all the
necropsies evidences of tuberculous lesions. The few attendants who, after
entering the serivce. develop tubercle may very well tlierefore have had
quiescent tubercle wliich w’as undiscovered on examination. Under any cir¬
cumstances the occurrence of tlie few cases of tuberculosis in a staff of over
2,000 cannot possibly be held to support any view that tuberculosis
possesses a degree of communicability which is in any sense comparable
with diseases such as smallpox, typhus fever and dysentery.

I.—Incidence of Tuherculosis .amonust Living Patients.

The first table, which is subjoined, shows the number of patients who
have been notified as suffering from pulmonary tuberculosis per 1,000
inhabitants in eight of the London County Asylums during the years
1904-1908 inclusive. The Epileptic Colony reports are for 190G-8 inclu¬
sive, and those of Long Grove Asylum, recently opened, only refer to 1908.
These statistics appear to show a gradual yearly increase, but it is probable
that the proportion for 1908 represents the more accurate figure, as many
cases may have been overlooked during the first few years of notification.
Where notification has been adopted in towns and cities a similar
apparent increase has been observed, although the measures adopted for

♦ By resolution of the Asylums Committee (11th November, 1902), it was decided that all
]>ermanent officials he medically examined before their appointment be confirmed. Since that
time more importance has been attached to the mctlical examination, and attendants and nurses
have been subjected to a minor examination before they have l>een taken on probation, and to
an examination in bed at the end of three months before their appointment has been confirmed.

74

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prevention of infection have increased and improved, as indeed tliey have
in the London County Asylums.

Tahle 1 .

Showing the total number of resident in tlie London County Asylums on

March 31.st of each year, with the proportion per 1,000 of those reported a.s
phthisical.

Number of

N umber of cases of j

Proportion per

i^atients resident.

Phthisis reported, j

1,000 residents.

M

1 K.

M.

E.

1

M.

F. M. A F.

March 31st, liMH

fJtC,

129

lH-2

11-7 10*2

..J

, 8,810

U9

1

20-7

1 ”>'7 17 H

. j

7,*2:W ,

9,85U

170

22*7

17-2 190

li^"7

7,;ui

l»,810

j U1 !

192

19:i

10-3 1 18-3

1W8 ,

1

00

10,714

170

217

21*2

20-2 1 20-7

1

We may therefore conclude that tlie probahle number of cases of
active pulmonary tuberculosis as diagnosed clinically among the insane
ill the London County Asylums is a little over 20 per 1,000.

The next table refers to the incidence at the various asylums during
the same period. There is a marked variation in the cases reported per
1,000 inhabitants. It will be observed that Claybury is more than double
any of the other asylums, and almost four times that of Cane Hill ; it is
not surprising that Cane Hill should report such a low incidence, for botli
the total death-rate and tlie percentage of active tubercle found pod
mortem are correspondingly low, whereas the total death-rate at Claybury
is not much higher, but the percentage of cases with active tuberculous
lesions at autopsy is very high. The variation which the table shows as
regards the resident patients sutt'ering from jiulmonary tuberculosis may
be explained to a small degree by the fact that some asylums more than
others remove cases from the tuberculosis list as the symptoms become
quiescent or subside, or on account of the diagnosis having been incorrect.
But this does not nearly account for the surprising differences, and
I consider that the personal equation of diagnosis is mainly responsible
for the wide discrepancy. Taking the returns from all the London
County Asylums, we find that 25 per cent, of the cases showing active
phthisis at autopsy are not diagnosed during life, and the difficulties in
the way of correct diagnosis are demonstrated by the following figures
from Claybuiv, where the necropsies are made by independent skilled
pathologists and microscopical examination is made in doubtful cases.

TriJEllC17LOSIS IN LONDON COI NTY ASVLl MS

75

During the iive years, 162 cases notified during life as phthisical have
come to autopsy; the diagnosis was confirmed in 111 cases (68’5 per
cent.), but in another 86 cases the presence of active pulmonary tuber¬
culous lesions was noted only at autopsy. As mentioned elsewhere, a
large number of the latter cases were general paralytics. Only those wdio
have had practical acquaintance with the diagnosis of pulmonary com¬
plaints in the insane can appreciate the many difficulties which arise in
large asylums in respect to the detection of tuberculous cases. Probably
if the post-mortem examinations had been made under the same conditions
at the other London County Asylums similar figures might have been
obtained. Tliis certainly shows the necessity of a more certain inode of
detection of tuberculous cases than at present exists, if isolation is to be
effective in preventing the dissemination of the tuberculous organisms,
either in the form of dust or droplets.

Table II.

Showiii^r the |)roj)ortioii per 1,000 of the patients resident in the various London
County Asylums reported as suffering from active phthisis.

Ban-

Bex-

Cane

Clay-

Colney

Han-

Hor.

The

the

Long

stead.

ley.

Hill.

bury.

Hatch.

well.

ton.

Manor.

Colony.

Grove.

Marclidlst, 1904

14-2

i:i-3

1 127

;|:5*()

1 !

1 12'" 1

14-9

13*1

13*3

«

*

1905

Ud

19-4

’ 8*9

38*1

I 17-9 1

15*9

l;}-;!

9-3

#

1906

16-0

2:M

8*8

42-9

1 21*4 1

16-0

11*8

7*7

1 *

1907

12-2

24*9 1

9*8

4<r8

19-1 !

16-2

13*4

11*4

9*2

*

1908

20-3 1

13*1

46-.1 j

22 2 i

1

161

1 ir>*i

11*0

8*9 1

! 17*2

!

Average ...

00

20*2 1

1

10*0

't0*3

18-6 *

1

15-6

13*3

10*5

&0

17*2

It is probable that the returns at Bexley represent about the average
incidence per 1,000 residents, namely, 20.

Time of diagnosis .—The majority of the cases, as Table III. shows,
are not diagnosed until some time after admission, and it would appear
that the disease in the majority of the cases had been acquired in the
asylum, but the post-mortem findings at Claybury and Colney Hatch,
where I made the necropsies for one year, do not, in a general way, bear
out this conclusion. As already pointed out, there are many difficulties
in the way of diagnosis especially in the early stages of the active disease,
particularly in the discovery of obsolescent tubercle.

76

ARCIllVKS

Tahle III.

Showing the time of diagnosis ot tubercle of the total number of reported tuberculous
patients resident in the London County Asylums on tlie 31st March of each year.

1

1

Arerage

!

1»0I.

1 1905. j

1906.

1907.

190s.

for

1 6 years.

Disejise diagnosed on ndinission

71

78

101

88

1-20

91-6

Disease diagnosed

witliin one

year of admission
Disease diagnosed

after one

4-1

44

53

40

42

45-8

year of admission

.1

i:>s

1>S2 j

181

100

231

190-2

Total ...

.1

•J73

304

i

i

335

1

333

393

, —

Seeing that one medical officer lias charge of 500 patients this disease
can easily be overlooked in the early stages, and attention may not be
called to a case until the symptoms become plainly urgent, and either
wasting or obvious illness is visible to the attendant or nurse in charge.
The patients themselves, as a rule, do not complain, but when a patient
becomes stuporose or melancholic, refuses food and loses weiglit—signs
of mental and bodily depression—then tuberculosis may be suspected and
looked for. In a great percentage of necropsies signs pointing to obso¬
lescent tubercle in the form of scars at the apices with caseous or cal¬
careous deposits, caseous or calcareous bronchial glands, or sometimes
mesenteric glands, and old pleurisy with adhesions are so frequently
found in association wdth active tuberculosis tliat it becomes a difficult
matter to decide Avhether the active disease is due to reinfection from
without, or reawakening of the original quies(^ent disease. Whichever
it be, the signs of obsolescent tubercle point to a soil that is suitable to
the growth of the tubercle bacilli; and with tlie lowei^d vita j^ropria of
the tissues the resistance has been so diminished that the patients are
unable to withstand the disease. Special attention has been given to
tliis point by the patliologists at Claybury' for the past six years. An
attempt has been made to approximate the length of time the patient has
suffered with the disease, a task difficult enough. It would be impos¬
sible, even after long experience, to give precise data, and no more can
be said than that the great majority of the cases appeared to have had
either obsolescent tubercle before admission or active tuberculosis on
admission. In tlie early stages of active phthisis, as is well known, the
disease may be discovered by systematically taking the temperature in

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

77

the early morning and late afternoon for at least a week. I am not
aware that this is done at any of the Asylums on admission of new cases.
A large proportion of patients suffering with active phthisis do not ex¬
pectorate, therefore the opportunity of examining their sputa does not
occur. I liave been surprised at the few specimens which have been
sent for examination, although an offer has been made to examine at the
Patliological Laboratory tlie s|)utum of any doubtful case.

Association with Mental Condition.
Table IV.

Allowing iiieiitjil condition of all reported tuberculous patients in the London County
Asylums, resident on the dlst March of each year.

—

UiOI.

1 lyoo.

i

1900.

1907.

1908.

Average

for

4 years.

Acute lusauity ...

Sb

4.9

5b

12

bo

52

Subacute lusauitv

i o

7

5

11

7

Chronic Insanity

LJ7

t 102

1111

122

129

117

Melancholia

101

106

101

12b

109

Gene ml Paralysis

r>

i 8

8

5

b

7

Epilepsy c. Insanity

15

1 19

17

22

21

21

„ c. Imbecility ...

*

7

7

b

11

8

Imbecility and Idiocy ...

17

1

•21

25

2b

21

Owing to the different nomenclature and classification employed at
the various Asylums, it was found very difficult to correlate the reports of
the mental condition associated with tuberculosis. It was therefore
decided to adopt the following classification: (1) Tubercle diagnosed
within one year of onset of mental symptoms; (2) tubercle diagnosed

within 12 to 18 months of onset of mental symptoms; (8) tubercle diag¬
nosed after 18 months of onset of mental wsymptoms. These are termed
respectively acute, sub-acute, and chronic insanity. Subsequent to the
first year of notification, the large number of cases returned as melan¬
cholia were collected under one heading. The cases of melancholia are
all cases of mental depression, and would include many cases of manic-
depressive insanity and dementia praecox, as well as melancholia. In
Table lY. it will be observed that melancholia figures largely as tlie
mental condition associated with tuberculosis; this is not surprising, as it

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may be supposed that the mental depression is correlated with a nutri¬
tional failure of the whole body, including the brain; the establishment of
a vicious circle occurs whereby mental de])ression and bodily depression
interact, the vita propria suffers, and micix>-organismal infection readily
takes place. There are many reasons that melancholy, and especially
melancholic stupor, should be associated with active tubercle. The
patients have no appetite or desire for food, they not only do not enjoy
their food, but often have a positive dislike for it or view it with dis¬
trust, and, refusing to take nourishment, they have to be fed with a
nasal tube; even when care is taken, some few drops of the fluid food
may find their way into the bronchial tubes and lead to broncho-pneu¬
monia. The general inertia of the patient is associated with shallow
respiration, enfeebled circulation, and malassimilatlon ; and there is a
depressive fall of all the vital energies, so that the resistance to tuber¬
cular infection is much diminished by the mental condition. The rela¬
tively few cases of mania with excitement as compared with melancholia
are striking. Imbeciles, epileptics, and paialytics are, for similar
leasons, susceptible to tubercular infection or reawakening of obso¬
lescent disease. The large number of cases of chronic insanity (disease
diagnosed some time after tlie onset of mental symptoms) include those
which, for the most part, show old tubercle at the /fost inortnri, and it
would appear that a reactivity or reinfection lias taken place with the
gradual lowering of the patients’ resistance, caused by the mental and
physical deterioration. The rej)orled incidence among paralytics is
slight, but reference to the pn:<t-in(nt(m statistics shoAVs that a compara¬
tively large number of paralytics exhibit active tuberculous lesions at
autopsy. Seeing that from ‘JO to 00 per cent, of the cases that come tc»
autopsy are patients who have suffered wdth this form of insanity, this
may account for the divergence of statistics of active tubercle found jwd
mortem at Claybury, as compared with other Asylums having an
efjually high total death rate, j^ro rata^ for the population. The tuber¬
culous process becomes active and progressive in the later stages of this
disease when there is marked mental and physical deterioration, but in
the majority of the cases there are signs of obsolescent disease, with
reactivity.

In the Asylums under the control of the Metropolitan Asvlums Botard
where chronic incurable lunatics, idiols, and imbeciles are housed, tuber¬
culous disease is more prevalent than in the London County Asylums.
{\ ide p. lOri). Belntively only a few epileptic imbeciles, imbeciles, and
idiots are resident in the London Countv Asvlums.

TUUERCVTOSTS IX LONDON COrXTY ASYLUMS

79

Aije at time of diagnosis.
Table V.

Showing the age at the time of diagnosis of tuberculosis of the reported living
phthisical patients in the London County Asylums on the ^ilst March of each
year.

Age.

1904.

1905.

1900.

1907.

1908.

Average
for five

years.

10-19 years

11

7

7

b

9

8

•20-29 „

47

.5(1

bO

70

57

W-29 .

K4

9b

lob

bb

1 10b

98

40-49 .

b:{ 1

74

81

' 9|.

, lUl

8b

.‘)0-.'.9 .

:>'i '

19 1

(•:;

bl

.50

lb '

2b 1

25

:U

1

2b

70-79 .

1

-I- ;

{)

1

b

.>

1

i

1 ;

1

1

1

1

i

1

It will be observed that, in a large number of the cases, tuberculosis
is diagnosed early in life (50 per cent, under 40 years of age); the
majority of these are cases of dementia prsecox, imbecility, and idiocy,
and cases of melancholia,—manic-depressive insanity. Reference to the
post-mortem statistics will show that these cases run a comparatively
rapid course and die early.

These figures do not include tlie cases in which the disease was diag¬
nosed for the first time at autopsy, but they give a fairly accurate pro-
poidion, for, whereas a number of general paralytics dying early in life
come to autopsy with undiagnosed tubercle, there is a balancing number
of cases of chronic insanity, dying later in life, in wliich an active lesion
is discovered for the first time at autopsy, the lesion generally being a
“eactivity of an obsolescent area.

Although the above statistics may indicate approximately the inci¬
dence of tuberculosis among the living patients and the relation to mental
disease, without reference to the records of autopsies, they are liable to
give rise to many erroneous conclusiojis, for a number of cases are diag¬
nosed for the first time post mortem, other reported cases show no evidence
of active disease at autopsy, and in many cases the mental condition may
so mask the physical symptoms of the disease that the date of onset is
not correctly stated.

I am unable to find any reliable figures regarding the incidence of
phthisis among the sane living inhabitants of London for comparison
with the figures giyen above.

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Deaths wifJt adive pulmonarij tuhercuhns lesions in the London Conniy
Asylums, Aprils 1903, to 3\st March, 1908.

The statistics for tlie past five years relating to the autopsies at all
the Loudon County Asyluiiis have been collected, and a summary of all
the cases of active phthisis has been made. The resuKs are given in the
following Tables: —

Table VI.

Showing for eucli year (1st April to 31st March) the total number of deaths, total
number of autoj)sies, and the total number of cases j)resenting active phtliisis in
percentage of total ]K*d-morlems.

Number of

Number of

Number of Deaths

Per cent, of Deaths with active

Deaths.

Post-mortems.

with active Phthisis.

Phthisis of total Post-mortems.

M.

F

M.

F.

F.

1

M. , F.

M.and F.

VMA

720

dbo

619

609

92

100

14-3 1 16-2

15-3

IIhi.t

76:{

627

660

bu

101

94

15-3 i 17-3

16-2

1IM >6

722

719

612

619

82

75

13-4 12-1

127

Wi)7

7i>8

708

724

601

103

100

14-2 14*4

14-3

1908

741

7:i8

668

682

88

122

16-2 i 17-8

15-5

Total

3.744 ;

3,545

3,304

:hl45

466

1 401

14-1 1 15-6

V.

Total M. & F.

7 28i>

6,449

057

. 1+8

During the five years April 1st, 1903, to March 31st, 1908, 7,289
deaths have occurred in the London County Asylums; autopsies have
been made in Gjll'D instances, and active pulmonary tuberculous lesions
found in 957 cases (400 M, 491 F), i.e., 14*8 per cent, of the total post¬
mortems, Of these tuberculous cases, 241 (127 M, 114 F), or 25 per cent.,
were not diagnosed during life, and it is interesting to note that 79
(62 M, 17 F) of these cases were ge. '*al paralytics.

The females appear to be more affected than the males, but the Clay-
bury post-mortem statistics (page 95) show that among the non-paralytic
population the males are more affected than the females.*

It will be observed that the incidence of tuberculosis at the various
Asylums shows a great variation. The causes of tliis variation may be
sought in the following conditions: —

1. The structure, mode of heating, ventilation, size of wards, and
cubic space allowed for eacli patient at each of the ten institutions;

* The monthly reports which durine: the past five years I have received from Banstead
Asylum, owincr to some misunderstaiidinof on tlic part of those who made the returns, were
incorrect, and I take this opportunity of statin^ that the statistics regardin'? tuberculosis in
that Asylum wliich have been published in the annual reports for the past five years are invalid.
The whole of these rG])orts were returned, and the Superintendent was kind enough to see that
they were amended.

Long

Grove.

The

Manor.

Epileptic
Colonj.

Total.

5r>

8

7

638

16

4

I-

250

6:3

11

14

505

1:3

3

1

164

55

2

6

447

40

10

11

591

47

0 ^

1,262

57

20

12

563

1:3

4

2

165

71

38

19

1,13(;

;36

14

6

628

ion

17

10

1,013

71

23

20

758

15

6

—

162

18

5

—

163

:3:3

18

4

418

27

21

373

61

53

11

808

42

14

1

4:33

36

6

8

354

33

1 29

9

431

103

' 50

28

1,232

8

4

1

161

41

18

5

560

87

42

34

852

94

63

15

1.154

81

77

20

1,158

26

10

12

374

46

9

14

548

45

11

11

405

84

13

—

540

1

1,578 i 650

1 329

! 18,246

1,578 i 650

18,246

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

81

2. The situation of the asylum as regards soil, altitude, and climatic
conditions, and time the patients spend in the open air;

3. The scale of dietary, the provisions for ensuring a milk free from
tubercular germs;

4. The type (age, sex, and class) of patients, and numbers of trans¬
fers admitted from out-county Asylums;

5. The personal equation of the superintendent and medical officers
at the various asylums in respect to the diagnosis of tuberculosis during
life, and the confirmation, or otherwise, yost morteviy which is apparently
by far the most important factor.

If there be a constant low death rate associated with a constant low
tuberculous death rate at a particular asylum, it may be assumed either
that the type of patient received in that Asylum is different, or that some
one or more of the conditions under Groups 1, 2, and 3 are more favour¬
able to the patients resident in that Asylum. For example, Cane Hill
Asylum has a comparatively low death rate and a low percentage of
cases which showed active phthisis at the autopsy. I have endeavoured to
ascertain whether the varying incidence of tuberculosis at the different
asylums could be attributed to any difference in the class of patient
admitted. The accompanying figures show the number of patients resi¬
lient in each London County Asylum on January 1st, 1908, chargeable to
tlie poor law authorities of the several London districts.

If we compare the two asylums that present the highest and lowest
mortality with tuberculosis (i.e., Claybury and Cane Hill), we find that
Claybury is chiefly inhabited by the insane brought from the east and
north-east districts of London, whereas Cane Hill receives mostly the
insane of the districts of South London, notably. Southwark and Lambeth,
which localities, according to Booth, are quite as poor as the eastern
districts. South London may be more salubrious than the East End,
but both districts have their poverty-stricken areas, with attendant over¬
crowding, &c., and I do not think there is evidence to show that the
difference in the type of insane inhabitant influences to any marked
degree the incidence of tubercle at the respective asylums. Moreover,
I find that all of the London County Asylums receive a good number
of patients taken from the more non-salubrious areas of London, and,
speaking generally and from observation, I should say that the various
asylum populations, on the whole, are practically of the same class. I
would make the exception of Colney Hatch, to which Asylum the Jewish
insane and the few young epileptic imbeciles housed in the London
County Asylums are sent. The Manor Asylum has nearly all female
patients resident, and presents a fairly high incidence of tuberculosis,
but this asylum has only 600-700 inhabitants, and is hardly comparable

F

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with asylums tlirice its size. The varying incidence cannot be attributed
to a different scale of dietary, for, practically, that is the same in all the
asylums; moreover, there is no reason to believe that the milk supplied
to the patients has been less liktdy to have been infective at the one than
the other asylum.

The difference in the incidence of active tuberculosis must be referred,
therefore, to either the structure of the respective institutions, mode of
heating, ventilation, size of wards, and cubic space allowed for each
patient, or to the site of the asylum as regards soil, altitude, and
climatic conditions. I regret that I am unable to give any reliable data
concerning the death rates from phthisis for the various asylum districts.

If we compare the two oldest asylums, Colney Hatch and Hanwell,
with Bexley and Cane Hill, we might assert that the difference was due
to the structure, &c.; but Claybury is a comparatively new asylum, and
as regards structure compares most favourably with any of the other
London County Asylums, we can only conclude, therefore, that a high
death rate, and the especially high percentage of cases of active tuber¬
culosis found i^ost mortem, may be partially associated with the site, soil,
altitude, and climatic conditions. Claybury Asylum is situated on a
hill, the soil is heavy clay, many of the airing courts are exposed to the
east wind, which blows across the damp Kssex marshes, and I think this
unfavourable cHmati(‘ condition may ])erhaps partially account for the
higher incidence of active tuberculosis found j)od mortem than in the
other asylums, e.g., Colney Hatch, Hanwell, and Horton Asylums, which
are also situated on clay. Banstead Asylum has apparently a low inci¬
dence of tuberculosis, and this we might attribute to its healthy site;
unfortunately, it has a high death rate, for which there may be the ex-
])lanation that diseases other than tubercle are more prevalent there than
at Cane Hill and Bexley, e.g., pneumonia, dysentery, &c.

As regards the low tubercular incidence, some cases of general para¬
lysis dying with active tuberculosis may be regarded as broncho-
j)neumonia. especially as I have found that cavitation is less frequent
with the tuberculous paralytic. (Vide Table XIII.)

Were it possible to eliminate the personal equation in the compila¬
tion of statistics, the facts here adduced would appear to point to the
general conclusion that soil, site, and climatic conditions are of consi¬
derable importance in reference to the incidence of tuberculosis in the
insane of the London County Asylums. Thus, Cane Hill and Banstead
(with the reservations mentioned) are situated on chalk hills, and the per¬
centage of cases which, at post mortem, showed active tuberculosis were,
respectively, 12‘33 and 10*85. Bexley, at a fairly high altitude, on gravel
and sand, has a ])ercentage of 11*83. whereas Hanwell and Colney Hatch,

Age (\t timp of Jet it It,

TUBERCrLOSIS TX LOXDOX COIXTV ASYLUMS

S3

84

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both ou clay and low lying, have percentages of 16*29 and 18*92 re¬
spectively. Claybury has a very high percentage, viz., 21*67 per cent.
At first glance these figures look very convincing against Claybury as
compared with Banstead, Bexley, Colney Hatch, and Hanwell, but the
total death rate at Claybury in proportion to the ratio of the population
is not higher than Bexley, Hanwell. or Colney Hatch. (Vide Table
VII.) But, in all these, the total death rate is considerably higher than
at Cane Hill. The probable explanation of the high incidence of active
tuberculosis at Clayburj^ as compared with the otlier asylums, except
Cane Hilly with its low death rate and low percen*age of active tubercle at
deathy lies in the fact that all the post mortems at Claybury are made by
a skilled pathologist, who gives special attention to the discovery of the
tubercle bacilli by microscopic examination in all doubtful cases of
broncho-pneumonia, and this applies particularly to the broncho-pneu¬
monia occurring in general paralytics, in which cases there is frequently
either an infection or else reinfection from obsolescent tubercle.

Table VIII. shows that over two-thirds (67*5 per cent.) of the deaths
with active phthisis in the insane die under the age of 50 years, also
that the maximum number of deaths with phthisis occurs between
30 and 39 years of age. It is well rec^)gnised that one of the great
characteristics of pulmonary tuberculosis is its tendency to attack and
kill those at the working, marriageable, and reproductive periods of life;
thus, in the case of the insane, it tends to eliminate the unfit at an early
age. Dr. Tatham points out that in England and Wales as a whole, and
in the urban group of counties, the age of highest mortality from tuber¬
culosis is at ages from 45 to 55 for males, and at 35 to 45 for females. In
the rural group it is from 25 to 35 for both sexes; but in the year 1905
the greatest incidence in England and Wales and in the urban counties
was 35 for females and 45 for males.

Comparison o f the Phthisis Death Rates at the several Afje Periods for the

Sane and Insane.

The subjoined Table, comparing the phthisis death rates for 1907 at
the several age periods per thousand living in London and per 1,000 of
the total population (18,872) resident in the London County Asylums has
been rendered possible by the kindness of Sir Shirley Murphy, who has
supplied me with tlie phthisis death rates at the several age periods per
1,000 sane persons living in London for 1907. I have also compiled a
summary of the cases from all the London County Asylums during 1907
in which phthisis was the cause of death; these figures have been obtained
by analysis of the post-mortem records, and also of the addition of the

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

85

few cases that did not come to autopsy, but in which phthisis was the
assigned cause of death.

Table IX.

Showing a comparison of the phthisis death rates for 1907 at the several age periods
per 1,000 sane living in Loudon, and per 1,000 of the total insane population
(18,872) resident in the London County Asylums.

Sane per 1,000 living.; Inpane per 1,000 living.

Insane Incidence.

Age period—

15-19 years

0-71

121

17 times as great as sane

•20-24 „

0*96

13-4

14

25-14

1-50

19-8

13

35^ „

2-49

151

6 „

45-54 „

2-92

61 ,

2

55-64

2*0/

7-8

3

65 years and OTer...

1-62

1

6*8 1

1

4

Totals .

1

1-33

i ;

i

8 times as great as sane

The following interesting facts may be deduced from the above Table ;
—(1) The much greater incidence of deaths from phthisis in adolescence
and up to 35 years of age in the insane than the sane; (2) the deaths after
45 years of age are only double those of the sane. It is, however, necessary
to qualify these figures by certain facts: (1) The majority of the people
admitted to the asylums are either bodily enfeebled, and with very low
powers of resistance, or are suffering with actual bodily as well as mental
disease; therefore, the probable average duration of life is infinitely less
than the outside population of the same class; (2) the sane population
would include all grades of society and not the pauper class alone; (3)
twenty-five per cent, of the people who die are general paralytics,
and these only live a few years after admission, and, as we have seen, a
large proportion, especially of the females, die with active tuberculosis;
(4) the statistics of the sane are not controlled by post-mortem examina¬
tion.

Consequently, the figures given above must be considered as only
approximate, and they probably over-estimate the incidence of tuber¬
culosis among the insane as compared with the same pauper class of the
sane. Still, however, these figures show that tuberculosis and insanity,
especially some forms of insanity, are intimately associated. The Table
also seems to show that insanity diminishes considerably the average
duration of life of the tuberculous individual.

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Rdctdl incnlenct of lubtrculosis. —l^r. liuLstrude, iu liis very interest¬
ing lecture at the Itoyal Institution, referred to evidence which w^ent to
show that the Irish sufter unduly from tuberculosis, even when they
have left their native land; and he contrasted the Irish w’ith the Hebrew
race, which, from the statistics available, appear to possess a marked
inununity to the disense. The Commissioners in Lunacy for Ireland have
called attention to this heavy prevalence of tuberculosis, and to the in¬
crease of insanity in that country. The former is regarded by them as
being due to the j>auperism, insufficient nourislnnent, and bad hygienic
conditions under which the people live, especially those who are “feeble¬
minded,'' and, therefore, less fit for employment and less capable of earn¬
ing sufficient money to obtain proper food. It is probable that the high
incidence of insanity may be due in a measure to the more mentally fit
having migrated to America; still, if there is a high incidence of tuber¬
culosis among the Irish-American population, it may be contended that
tlicre is a racial tendency to the development of phthisis.

Colney Hatch Asylum receives all the Jewish insane, for the most part
alien. 1 therefore determined to see how these Jewish lunatics com¬
pared with the Christians as regards incidence of tuberculosis. I was not
able to control the result by the data obtained on the post-mortem table,
for Jews are all “conscientious objectors.” Still, the results are of
interest. I am much obliged to Dr. Seward for furnishing me with the
following (lata: “The total numl>er of Jewish patients who died during
the five years (A])ril 1st, 1903, to ilarch 31st, 1908) was 75 males, 69
females ; total, 144. Of these, 21 males, 16 females, total 37, had active
tuberculous lesions. As very few post-mortem examinations are made in
the case of Jewish ])atients, it is necessary to make some allowance for
a few cases in which the disease may not have been recognised during
life."

J'bis niak(‘s 2')‘7 per cent., which rather under-estimates the number,
y(‘t it exceeds considerably the incidence among the Christians at Colney
Hatch Asylum, whicli, for the same period, and controlled by
mortcm examinations, was IS’O per cent. It may be asked how we account
for this I think it is because the Jewish patients are largely composed
of aliens who have not been long in this country; they come from Eussia,
foi- iho most part, where they and their progenitors have lived in great
paupc'iisni and degradation, and, therefore, unlike the prosperous Jews,
whose progenitors settled in this country several generations back, have
already the ‘Jeeds and soil of consumption in their bodies when they arrive
in this country.

TlBEfiClLOSlS IN LONDON COUNTY ASYLUMS

87

Prof. Karl Pearson, from his investigations upon inheritance, comes
to the following general conclusions as a result of his study of the sta¬
tistics of pulmonary tuberculosis: —

“ (rt) What 1 have spuken of as ihe diatliosis of pulmonary tuberculosis is
certainly inherited, and the inteiidty of inheritance is sensibly the same as
that of any normal physical character yet investigated in man.

Infection probably plays a necessary part, but in the artizan classes of
the lirban populations of tliis country, it is doubtful if their members can
escape the risks of infection, except by the absence of the diathesis, i.e., tlie
inheritance of what amounts to the counter-disposition. The probably earlier
age of onset, at least in certain cases of family history, as compared with
those cases without family history, cannot at prt^ent be definitely asserted to
be due to parental infection. Tn the statistics we are dealing with, the bulk
of the i)arents must have passed the danger zone before the onset to the
offspring (average age: 29 for males and 2o for females), and further, many
such offspring will already have left in the artizan classes the immediate home
environment. The earlier age of onset in the children is probably associated
with the same tendenc}- to earlier inheritance noted in cases of cancer and
defective vision and possibly in gout, rheumatic fever and diabetes, where the
question of infection hardly arises.

I feel fairly confident that for the artizan class the inheritance factor
is far more important than the infection factor, because in a very larg<‘
proportion of cases it do-^s not lie in Ihe power of the individual to maintain
in the stress of url)aii life a wholly safe environment.

“(b) There is no reduced fertility in the case of tuberculous st-ocks, in fact
their fertility is as groat as that of any other class in the community, and
markedly greater in artizan tul>erculons stocks than in any class of brain
workers.

“ (c) In general, whether wo deal with all tuberculous sbxjks, or only with
those having no paiaaital history, the elder c»ffspring, especially the first and
second, appear subject to tuberculosis at a very much higher rate than the
younger members.

“ The one certain rule of racial fitness is the preservation of the dominant
^‘productivity of the mentally and physically fitter stocks. In less civilized
communities than our own this is roughly provided for by the struggle for
survival within the race and between races, and by the fight against organic
environn;ent and against physical environment. As far as statistical facts
as to inheritance, fertility and survival in civilized communities are at present
known and available, the dominant reproductivity of the mentally and
physicaly litter stocks appears likely to be more and more weakened by (1) the
lessened intensity of the intraracial stniggle, and (2) the differential limita¬
tion of the family.

“ Can we consciously do what in the past was unconsciously achieved; can
we pre.serve this dominant reproductivity of the mentally and physically fitter
stocks? If this is to bi* clone at all, we must patiently continue to collect data
as to disease^ inheritance, and fertility in man. There must, be a healthy
Co operation IWween medically and statistically trained minds, and when
the evidence is, as I believe it will Ije in the near future, overwhelming, then
there must he a iiniled effort of Iwth to influence public opinion in favour

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Jirst of a few siiiipli" rules uf conduct for those social hy nature, and then, if

necessary, a further united effort in favour of legislation to restrain those

anti-social by inheiitance or nurture.’’

The reports furnished in the system of notification at the asylums did
not yield sufficiently reliable data to prepare any useful statistics, and,
though I possess at present no precise data, yet I am of opinion, from
experience, that inheritance of a soil suitable for the development of
tuberculosis is associated so frequently with certain forms of insanity,
notably those with mental depression and which begin when the repro¬
ductive functions commence, that although I do not consider Clouston is
warranted in speaking of a tuberculous insanity, jjer se; nevertheless,
a metabolic failure at the reproductive period is at the basis of both the
insanity and the tubercular infection. At this period of life the specific
vital energies of all the somatic tissues are subjected to a test of their
fitness to fulfil the reproductive functions, and provide directly or in¬
directly the necessary nutrition for the offspring. All the metabolic
activities are increased, especially of the highly complex phosphorus-
containing substances; the nucleo-proteids and lipoids.

Dr. Tatham says: ** In both sexes it is with the approach to maturity
that the real liability to death by phthisis begins, and this is true of
recent as well as earlier years.'’ In persons who do not inherit an insane
temperament, an invalid brain, the existence of tuberculosis does not
lead to failure of the nutrition of the brain, unless there be actual tuber¬
cular infection of that organ. It is not surprising that the brain in¬
herently sound should not suiter materially in its functions from mal¬
nutrition, seeing that it Joes not undergo wasting in starvation or the
most severe forms of anaemia; unless there be marked toxaemia or
pyrexia, or, as generally happens, the two combined, no mental disturb¬
ance occurs. This may be explained by the fact that the 'preservation of
the individual necessitates the preservation of the most noble master
tissues, even at the expense and destruction of the less noble tissues which
are its servants. Again, the preservation of the species is instinctively so
powerful that tuberculous individuals, though not possessing sufficient
vital energy and nutritional reserve to maintain metabolic equilibrium
and resist the invasion of the tissues by the tuberculous organism, never¬
theless, do not suffer as regards fertility until the disease has advanced
to an incurable stage. It is probable that the inheritance of a soil suit¬
able for the development of the tuberculous organism is dependent upon
some metabolic failure which is transmitted. There is some evidence to
show that in the case of dementia prfecox, there is transmitted also a
metabolic failure of the brain itself. {Vide paper by Dr. Koch and Mr.
Sydney Mann).

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

89

Sir Hugh Beevor advances the proposition that it is the power of the
growing lung to resist infection which determines different incidence of
the disease on sex at early ages. At a time when most persons are highly
prone to nearly all the specific infectious diseases, and when the lungs
are, he thinks, exposed to tuberculous infection as much as at any other
age, the death rate from pulmonaiy tuberculosis is relatively insigni¬
ficant. It is, in his view, the full-grown lung of the girl of fifteen years
of age, which, having lost its resistance to the tubercle bacillus, leads to
the death rate of the 15-year-old girl from phthisis being equal to the
boy at 17. But the 15-year-old girl is sexually mature, and the sexual
instinct is stirring to the full degree the vital energies of all the tissues;
this sexual instinct develops later in the boy, and I conceive that it is
this instinctive change in the metabolic activities of the somatic tissues
to provide nutrition for the reproduction and preservation of the species
at an earlier age in the female than the male, that lowers the powers of
resistance to the tubercular organism of the inherently feeble.

Incidence of phthisis amongst asylum officials .—All employes in the
London County Asylums are now subjected to a medical examination
before admission to the service {vide footnote, p. 73), consequently it
is to be presumed that few if any cases of active phthisis enter the ser¬
vice. The medical examination is now enforced, but it was not in past
years.

Table X.

Showing tlie approximate length of Service of the Attendants and Nurses in the
various London County Asylums in October, 1908.

lienpth of Service.

Under 1 year
1 year to under 3 years

3 years „

. 5 .

5 .. „

, 10 .

10 ..

, 15 .

16 ..

, 20 ..

20 ..

, 25 ., .

25

, 31 „ ..

Total ..

Male Attendants.

1

llesideut.

Non-resident.

139

6

195

:!8

50

6:{ ,

74

213 !

8

103 1

5

05 1

3

20 !

j

16 ;

j

480

553 1

Total.

Female

Attendants.

Total
M. i I

Resident.

145

400

54^)

233

39()

829

109

108

307

287 !

! 220

507

Ill

i ,

193

ion

40 '

149

32

17

49

10

4 .

20

1,033

1,366 1

2,399

It will be observed that 52 per cent, of the male attendants, and about
30 per cent, of the nurses have been in the service five years or more.

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There are about 2,400 attendants and nurses eiupluyed in the London
County Asyhinis, and at present the following five cases are notified as
phthisical: —

Date of entering- Date of diagnosis
Service. of Phthisis.

(Jlav IU'KV—

Alt. A. C. ... ... May, 'Oo ... Xou at work in ward.s. Di.'^ease

(juie.sceiit.

Att. J. C. ... 23-2-01} ... *2-5-0:)

Nurse A. P. ... *24-7-04 ... ? ... ,,

CoLNKY Hatch-

Att. W. tv. ... 1-5-90 ... jil)Out 1896 ... Now at work in wards. Digea.'^e

(luiescent.

Att. I).23-9-02 ... 10-0-07.

Tims, of these five ca.ses present on the list as presumably tuberculous,
four have resumed their duties in the wards, the disease being therefore
quiescent, or the diagnosis was doubtful.

With regard to the incidence among the staff in past years, and also
the question whether the disease was acquired while in the asylum ser¬
vice, I have received the following replies from Ihe various medical
superintendents: —

Dr. Johnston Jones, Hanstead Asylum,

States that three attendants and seven nurses have suffered with tuberculosis
during the past fifteen years. The family hishny in each of thes<* cases
showed a strong tendency tx) the disease. In his opinion no nui*se or attendant
has acquired the disi‘ase in the service.

Dr. Stansfleld, Bexley Asylum,

Has reported the following cases during the past live years: —

Entered Service. Tubercle Diagnosed.

Att. H. G. ... ... 1*2-9-01 ... Nov. *05 ... Given 3 months leave and then

left service.

Att. A. E. 13. ... *20-6 ... 12-4-06 ... Left service Au^^st, 1906.

Nurse G. S. ... 16-8-00 ... Left service 31-1*2-03.

Nurse G. ... ... *21-5-01 ... 5-3-03 Left service March, 1903.

Nurse P. M. S. ... 23-t>-05 ... Nov. '05 . Left service January, 19tM).

Dr. Moody, Cane Hill Asylum, states: —

“ As far as I am aware no attendant or nurse at luvsent here is suffering
from tuberculosis. Since the opening of the Asylum (1883; I can remember
two nurses and two attendants who had the disease, but as we did not examine
officials before entering the service I cannot say if they acquired it here or no.’*

Dr. Robert Jones, Clayhury Asylum : —

“ During tlie la^i Hve years, 1904-8, five male attendants died of pulmonarv
tuLovulosis ; one lias left the service from th(‘ same caiisx*. whilst three remain.
These three have each been resident in a sanatorium for at least three months,
and the symptenns of tuberculosis are at present in abeyance.

Tl iU:UCi;L()SlS IX loxjkkx coi nty asvli ms

91

No iiiirs<* has died in the Asylum from tuberculosis, but several have died
after leaviuii; the service, which they did through ill-health, viz., tuberculosis in
the early stage.

It is susi)ecteil that at least three other nurses are at present suffering from
tuberculosis.

1 consider the soil of the Asylum site s<jinewhat favours tuberculosis, being
heavy clay and subject to undue mists and frequent fogs from the river and
low-lying flats.

The medical examination of candidates for .\syluin service excludes cases of
definite tuberculosis, but in the early stages it is no easy matter to be dogmatic
as to the presence or otherwise of tuberculosis. The fact that a medical
re-examination is made at the end of the six months’ probationary period
certainly tends further to exclude this disease from amongst the staff, so that
those who contract it do so most probably from the nature of their work and
suriHuindings.

That this percentage is small among the staff may l^e gatliered from the fact
that there are about 157 femah» and 13d male attendants, but to fill tliese posis,
during the five years, 270 nurses and 145 male attendants have been engaged—
a total of 415 persons, so that there has Iwn considerable fluctuation among
the resident staff. Of these, 81 attendants and 42 nurses have l^een in the
service over the five years referred to, being in the projmrtion of 61 per cent,
ami 27 pt‘r cent, respectively of the male and female attendants. ’

Dr. Seward, Coliiey Hatch Asylum,

Reports the following cas<‘S among the staff, and is of the opinion that two
attendants who were employed in an insanitary ward probably acquired the
disease in consequence.

I.N'CIDKNCE OF d’cBEKCULOSIS A.MON(i THK MaLK ATTENDANTS AND Nl'USES.

All Attendants and Nui*ses are carefully examined Ix^fore joining the service, and
those mentioned below were passed as healthy.

Name.

^ Coiiiincucenient of Service.

1

Terininatiuii of Service.

Att. J. M. ..

.. 2nd March. 1877 .

1st February, 1888 (resigned).

Att. J. C. .

7>th Api-il, 1878

30th 8e]>teml)er, 1888 (resigned).

Nurse B. A. G.

1st January. 1889 ...

19th May, 1890 (resigned).

Att. A. J. ..

.. Tith May, 1890 .

28th June, 1890 (unfit for dutv).

Att. W. A. W.

1st April, 1887

8th June, 1891 (died).

Att. J. J. .

1st Marcli, 1880

2nd July, 1895 (died).

Att. A. B. .

31 St J anuary, 1883 ...

25th 8eptember, 1896 (died).

Att. E. F. ...

9th Dcceiuher, 1882...

17th July, 1899 (died).

Att. (I. B. ...

17th December, 1894

5th March, 1902 (died).

Att. E. A. ...

... 29tli November, 1904

10th October, 1908 (died).

Att. W. AY.

... l.st May, 1893 .

Still in the service.

Att. H. D. ..

...1 23rd 8e])tendjcr, 1902

Still in the service.

AY. J. SEWARD,

Modind Sif 2 ) 0 rIntnndrnl.

mh Uctoh^r, lf^U8.

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Dr. Bailey, Hanwell Asylum,

Reports the following cases: —

Nurse A. H.
E. C.
,, N. V.

Date of entiy Date of diagcosie

to service. of tabercle.

... 26-7-88 Dec. 1902 ... Left service 16-11-08.

... 22-^3-06 ... Dec. 1906 ... Left service 11-2-07.

... 19-9-99 ... Jan. 1907 . . Left service 27-4-07.

The last two have since died.

Att. J. W. G.

W. F. .
„ G. H.P.

16-12-96 ... Sept. 1904 ... Died 28-1-05.

5-8-01 Sept. 1904 ... Withdrawn from list 80-1-^>6.

15-4-01 .. March 1906 .. Died 12-8-06.

Dr. Lord, Horton Asylum, states: —

Regarding the prevalence of phthisis amongst the staff, my short
experience at this asylum does not permit me to give you exact figures, but
speaking generaUy I think it is a comparatively rare thing for nurses and
attendants to acquire the disease. I understand that here there have been
three or four attendants who have suffered from phthisis, but in every case a
strong family history of tuberculosis was present, and there was a degree of
doubt as to whether or not the seeds of the disease were not sown prior to their
admission here. Only one attendant has been reported as phtliisical since I
have been here, but the signs in the lung were indefinite; and after his death
I was told that he had suffered from cancer. One of the nurses who has a
strong tubercular history, had an irregular temperature for some months
during the early part of the year without any pulmonary signs.”

Dr. Donaldson, Horton Manor: —

“ I append herewith a list of nurses wdio left the asylum service owing to
having developed phthisis: —

Date of Date of

joining service. leaving service.

Nurse K.M. ... 28-8-02 ... :ll-12-02

Nurse A. P, ... 7-8-02 ... 5-8-02

Nurse A. R. J. ... 16-7-06 ... 11-8-07

The above-named were all medicaUy examined on admission, and no signs
were detected, although in some of the cases the disease may have been latent.
A nurse, E. P., who was here from 8th March, 1903, till 13th July, 1906,
resigned owing to ill-health; there was a suspicion of phthisis in her case. I
believe also that an attendant, J. G., who joined here on the 28th August, 1899,
and left on the 7th November, 1900, developed phthisis whilst here. I am
unable to inform you definitely with regard to his case, as he left the asylum,
owing to ill-health, before I came here.”

Dr. Spark, The Epileptic Colony: —

“ No attendant has to my knowledge acquired phthisis at the Colony.
There is at present an attendant with an abscess, possibly of tubercular origin,
but I do not consider that the tubercle has been acquired in the Colony.”

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

93

l)r. lioud, Long Grove Asylum, opened June 18th, 190 < : —

“ No member of the st^ff has so far contracted tuberculosis since entering
the servioe.-

It will be observed that, of the cases noted, the majority developed
the signs of tubercle after a sboid. period of service, three years or under,
some few, indeed, died of the disease within 6 to 18 months of admission.

Table XI. shows the approximate length of service of the inspectors,
matrons, and head attendants in the London County Asylums. It will
be observed that nearly 90 per cent, have been five years or more in the
service, and the majority 15 years or more. Now, those who have had
twenty years’ service, and they are 51 out of 137, have been located—at
any rate, for a great part of their service—in the old, and, presumably,
less sanitary asylums; yet, they have not been infected, or, if they have
been, they have undergone spontaneous cure, for I have not heard of a
case of tuberculosis occurring in a head attendant.

Table XL

Showing the approxinnite length of Service of the Matrous;, Inspectors, and Head
Attendant.s in the London County Asylums.

Length of Service.

.Male.

Female.

Total.

Hnder o years

3

12

1.5

•5-10 years

10

22

32

io-i:> „ .

(>

U

20

l.>-20 .. .

()

13

10

20-25 .

11

1.5

2t;

25-30 .. ... .

10

18

30-35 .

•5 1

— -

1

Over 35 yearK ... ... 1

1 2 1

1

—

2

Total . .. !

_i

1

HO

! 1.37

[

It is impossible to compare these statistics with the outside popula¬
tion, but if asylums were as infective as was supposed by the report of
the Medico-Psychological Association, one should have expected a much
higher incidence of tuberculosis among those employed for 14 hours
daily in actual attention to the lunatic. Moreover, length of service
appears to point to freedom from tuberculosis among nurses and
attendants, for the disease was recognised in those reported, in the
majority of instances, during the first few years of service.

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II.— Summary of Statistics R?:LATiN(r to Tuhekculosis found

laoriem AT Clayhury Asylum from Septemhfr Isr, 1898, to AuciUST
31st 1908-

The records of tuberculosis occuriiiig in the bodies of nearly all the
patients dying at Claybury Asylum during the above ten years may be
summarised 'as follows : —

All the necropsies have been made by the pathologist or his assistants
during that period. In 90 per cent, of the total deaths an examination
has been made, and the observations systematically recorded. In every
case every organ, including the bowel, has been carefully examined, and
particular attention has been paid to discover the existence of obsolescent
tubercle. In cases of doubt, examination for tubercle bacilli has been
made.

During that time 2,203 (1,075 M., 1,128 P.) deaths occurred, and
necropsies were made in 1,982 cases (901 M., 1,021 F.). Active tuber¬
culous pulmonary lesions were found in 215 female and 201 male cases;
total, 410, i.e.y 20*9 per cent, of the total f)Ost morlnns (20*9 per cent. M.
and 21*0 per cent. F.).

Pulmonary tuberculosis was judged to be the primary cause of death
in 323 cases (149 M. and 174 F.); 10*3 per cent, of the total post mortems
(15*5 per cent. M., 17*0 per cent. F.).

This figure does not compare with the percentage mortality on the
total deaths from all causes for the ten years (January 1st, 1898, to
December 31st, 1907) given in the Commissioners’ Report, but the dif¬
ference can be explained. Firstly, there must always be some difficulty
in deciding wdiich is tlie primary or immediate cause of death when two
or more factors are concurrent. Secondly, there are a number of cases
in which the symptoms of tuberculosis are masked by the mental condi ¬
tion, and in which tuberculosis, altliough sufficiently advanced as to
cause death, is not diagnosed except at autopsy. It will be seen, on
reference to the statistics of the association of tuberculosis with mental
condition (p. 101) that a good proportion of general paralytics die with
active tuberculosis; the disease in these cases is hardly ever diagnosed
(luring life (p. 80), and, although in manj’ cases it is jiurely a secondary
associated condition, in many others it is extensive and active enough
to have been correctly assumed to be the primary cause of death. The
above figures are taken from actual post-morUm records, and in each case
—if the tuberculous lesions alone were judged sufficient to cause death,
tuberculosis was assigned as being the primary cause. The personal
ecpiation of the various medical officers at the London County Asylums,

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

95

other than Claybuiy, who eacli Diake autopsies on their own cases, must
vary considerably in respect to this important point of deciding in cases
of general paralysis whether it should be recorded that the patient died
of general paralysis or concurrent tuberculosis.

Tuberculous ulceration of the intestines was found in 73 males (36’3
per cent.) and 115 females (53*4 per cent.) of the cases dying with active
tuberculous lesions; in the latter cuvse the higher percentage is possibly
due to the fact that females are more apt to swallow their sputum than
males.

'Paulk XI f.

Showing the incidonoo of phthisis amongst general paralytics, with comparison,
according to the age at death, with the incidence of phthisis among non-
paralytics during the ten years 1-9-98 to 31-8-08.

Fifty years of age
and under at death.

M

4t)S

129

Over 50 years of
age at death.

M. ! F.
493 I o92

I ht)
' 11 1

F. M.AF.

429 897

149 i 278 I 72
347 30-9 140

Total number of antop.^ies ..
Total number with active
phthisis

Percen ta ge w i t h a c t i ve ph 111 i s i s

Total number of general para-
13 -tics ...

Total number of general para-
13 ’tics with active phthisis .
Percentage of general para-
h’tics with active phthisis

Total number of non-paral vr ics
Total number of non-paralytics
with active phthisis
Percentage of non-paralytics
with active phthisis

•274 j

llo

[ :«4

82

23

r >2

30

! 82

1

8

1 -

18-9

1 27-4

! 2P3

]

97

217

194

319

' 513

411

1

' 569

119

19b

64

(;i

39 b

37-3

:18 2

15*5

10*7

1

Total.

M. F.
1085

M.

961

F.

1021

.V[. k F.
1982

138

127

201

20*9

215

21*0

4d;
2( >*9

105

356

133

•189

13

60

35

95

12-3

16*8

2t)-3

19'4

980

605

888

1493

125

141

180

3>21

12*7

23*3

20-2

21-5

The onset of general paralysis occurs usually in the third or fourth
decade of life, and death occurs in the majority of cases before the patient
lias arrived at the age of 50. If we wish to make a fair comparison
between the incidence of active tuberculo.sis at death between general
paralysis and other forms of insanity, we should compare corresponding
periods of life. The above table shows that in 1,982 jfost-mortem exami¬
nations, active tubercle was found in 20*9 per cent., the female incidence
being practically the same as the male, viz., 21*0 and 20*9 per cent.;
but if we take the non-paralytics, we find a higher incidence among the
males, viz., 23*3 per cent, males and 20*2 per cent, females, and this

96

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agrees with the relationship of pulmonary tuberculosis in the outside
population, where the males preponderate. Among the general para¬
lytics we find a reversal of this order of things, viz., 16*8 per cent, males
to 26*3 per cent, females, and it is this difference which makes the total
female incidence of active phthisis found fost mortem very slightly in
excess of the male incidence. Now we may ask the question, why should
female general paralytics show a higher incidence of active pulmonary
tuberculosis mortem ? Is it because there is more liability to infec¬
tion in the Asylum? I think not, for, as a rule, female general para¬
lytics live longer after admission than males; I consider the answer is
afforded by the relative social position of male and female general para¬
lytics. It is well known and acknowledged that the higher we rise in
the social scale, tlie less frequently do we meet with this disease in
females. Vice versdy the lower we descend in the social scale, the more
prevalent does it become, so that in the pauper classes the ratio of general
paralytics is about three males to one female, perhaps less for a consi¬
derable proportion of the male paralytics admitted as pauper lunatics
have only become paupers since the onset of the disease which deprived
them of their money, their business, their occupation, and, in not a
few cases, their profession. I have been struck by the.fact that, whereas
the friends who visit male paralytics frequently belong to the middle
as well as the lower classes, it is seldom that the friends of the female
paralytic belong to the middle classes. Many of them, although spoken
of as married women, belong, or did belong, to the unfortunate class
who earn their living by prostitution, and are not visited by friends.
The frequency with which one finds non-tuberculous adhesive inflamma¬
tion of the oviducts (50 per cent, of the total female general paralytics
that die) lends indirect support to tliis contention. Another interesting
fact, which Dr. Watson and I observed in the comparative examination
of a large number of brains, w’as the relatively inferior convolutional
pattern and weight of the brains of female general paralytics as com¬
pared with male paralytics. Quite 30 per cent, exhibited a convolu¬
tional pattern indicative of defective mental endowment, as if their pos¬
sessors belonged to the congenital feeble minded. It is generally acknow¬
ledged that syphilis is the cause of this disease, and the history of
sterility, miscarriages and still-births which is so frequently found in
female general paralytics, together with other reasons, supports the
contention that the reason that the female paralytics show a much higher
incidence of active pulmonary tuberculosis than the males does not rest
upon the fact that they are more likely to acquire the ,wils of tubercu¬
losis in the Asylum, but that the social conditions under which a good
number of them lived prior to admission, of exposure to cold and wet,

TUBERCULOSIS IX LONDON COUNTY ASYLUMS

97

of iusufiicient nourishment, povertxjy overcrowding, and alcoholism, com¬
bined with an inborn mental and physical deficiency in a considerable
percentage, produced a more suitable soil for the development of tuber¬
culosis.

In the doth Annual Report of the Local Government Board, 19U5 and
1906, Dr. Bulstrode remarks: “ Although there are doubtless many

factors influencing the prevalence of tuberculosis, there is one that stands
out prominently above all others; this factor is poverty, and although
it is matter for dispute which elements of poverty are mainly operative,
til ere is much evidence in support of the view that poverty as a whole,
with all that it comprises and implies, may be regarded as one of the
most, if not the most potent predisposing causes of the malady.’’

Sir Shirley Murphy, in his reports, has called attention to the cor¬
relation of pauperism and overcrowding with tuberculosis in various
districts of the County of London.

The increasing death rate from tuberculosis in Ireland in association
with a high total pauperism and increase of insanity points to pauperism
being productive of both conditions, as the Inspector in a supplement to
the 54th Report of the Inspectors in Lunacy says: “ It would seem not
improbable that the innutritions dietary and other deprivations of the
majority of the population of Ireland must, when acting over many
generations, have led to impaired nutrition of the neiwous system, and
in this way developed in the race neuropathic and psychopathic tenden¬
cies which are the precursors of insanity.”

Tatu.k XITl.

Sliowing perreiitago of cases of active phthisis found pos/ niortnm during the ten
3 'ears, 1-9-98 to Jll-8 08 with cavitation. Comparison of paralytic and non-
])aralytic cases.

—

1

Xon-paralytic.'i.

General Paralytics.

1

To no.

Nuinl)er of cnses

with

M. F.

1

__ 1

-V.iF.'

1

1

M. ^ F. M.A’F. M.

F.

1

i M. 2c F.

1

active phthisis
Number of cases

i

witli

i n 180 ;

1

:121 1

00 1 o:, 201

1 - v ,

: MO

1

cavitation

Per cent- of ca.ses

with ,

88 MV.] '

1

221 '

1

:i2 19 r,i 1-20

* l.'.i

!

1

cavitation

1

... 1

1

62-4 7:V8 1

68-8

r>4:i odo 597

1

i 70-7

j

In Table XIV. it will be obseiwed that practically 25 per cent, of
fhe cases of deaths with active phthisis occurred within a year of admis¬
sion to the asylum; even if allowance be made for the fact that the
combination of the mental affection with the bodily disease hastens the

98

ARCHIVES

fatal termination, it is more than probable that tubercular disease either
preceded or coincided with the onset of the meutal symptoms.

Tahli: XIV.

Showing the length of residence in Asylum of the caso.s dying with active jdithisis

during the ten years, 1-9-98 to ill-8-08.

Length of reKidence.

Males.

Femiiles.

Totals.

Under 3 months ..

It)

13

29

3 month.s to under

0 months

21

13

34

9

11

10

21

..

11

'>

16

18

19

15

34

IH

*2 years.

13

17

30

2 years

:i ■

25

29

54

:! „

4

18

25

43

4

10

20

30

5 ..

0

11

10

27

6

7

12

19

31

7 „

8 ,,

12

9

21

8 „

9

4

7

11

10

4

7

11

10 years atid over...

14

10

24

Totals ...

201

215

416

Of 416 cases of patients dying with active pulmonary tuberculosis
164 died within two years of admission; it is probable a priori that the
great majority of these patients suffered with tuberculous lesions on
admission, albeit the disease was not diagnosed on admission in a large
percentage of this number. It will be observed that practically 70 per
cent, of the cases died within five years of admission to the asylum. In
tile next five years we have a marked drop in the deaths, which decrease
does not accord with Dr. Chapman's deduction based upon the statistics of
the Medico-Psychological Association, viz.: “ The cases of tuberculosis in
asylums inhere in the asylums themselves and not in the character of the
patients sent to them^ If this were correct tliere should be a steady
increase of the deaths with active tuberculosis for each year of residence.
Colney Hatch is the second oldest (opened 1851) of the London County
Asylums; and when I made the jfost-mortem examinations there for one
year I had the opportunity of examining the bodies of patients who had
been in residence from 30 to 50 years, and I did not find in some of these
a trace of tubercle. I cannot therefore agree with Dr. Chapman’s deduc¬
tion. My contention, moreover, is supported by the io\\ow\n^ post-mortem
records: —

Tl HERCFLOSIS IN LONDON COFNTV ASYI.I MS

99

Table XV.

Showing incidence ot‘ ob-solescent tuberculosis without active disease in total
liOHt-mortemH at (.Uaybury Asylum during the six years, 1-T 02 to 31-3-08.

Signs pointing
to obsolescent disease.

Active disease.

Nil.

Total.

M. P.

M. 1 P.

1

1

1 j

F.

M.

F.

I7i> lO

122 j 122

2b 7

!

1

2b

:>b8

530

'I’oials...

244

531

1098

Thus 323 cases, or 29*4 per cent. (31*5 per cent, males and 27*1 per
cent, females), showed signs of obsolescent pulmonary tuberculosis
without any active disease; active or obsolescent lesions, or both, were
found in 51*6 per cent, of tbe total pod moiicrns.

Table XVT.

Showing probable time of infection of the ca.ses dying with active pulmonary
tuberculosis at Clay bury Asylum during the six years, 1-4-02 to 31-3-08.

Probably infected before
admission.

Probably infected after
admission.

Doubtful,

Total.

M.

F. ! M. F. M. 1 F. M.

1 '

1 F.

77

no

1

13 ■ 12

1

1

:>2 j 20 1 irj

122

'rOTALS... 107

25

1

0-2 j 244

Thus in only 10*2 j)er cent, of the euses with active phthisis at autop.s}"
was it inferred by post-morfcm examination that the disease had been
acquired in the asylum.

The above tables are based upon the records of autopsies made at
Claybury Asylum; they must, however, be considered as only affording
approximate truths, for there are many and varied difficulties of deter¬
mining accurately the data upon which they are based. If a patient, on
the one hand, has been a short time in the asylum, and we find evidence
of obsolescent tubercle there is no difficulty in asserting that the patient
had suffered with the disease before admission, even if there be asso¬
ciated active disease; it does not, however, prove whether tbe reinfeetion
was from within or from without; all that it shows is that there was a
suitable soil for the seed to grow upon. On the other hand, if the patient

G 2

100

ABCniVES

(lies some few or more years after admission it may be very difficult to
decide whether the obsolescent tubercle should be regarded as evidence of
the patient having suifered with tubercle before admission. Still, the fact
that d23 cases, or 29*4 per cent. (dl*5 per cent, males and 27 1 per cent,
females), showed signs of obsolescent pulmonary tuberculosis without any
active disease indicates that a large percentage of the residents in the
asylum have a soil suitable for the development of tuberculosis, yet have
not developed active disease by infection from without. iTiis does not
support Ur. Chapman's contention that the majority of the cases of
pulmonary tuberculosis in asylums are due to infection owing to causes
inherent in the asylums themselves, otherwise we ought to find relatively
only few cases of spontaneous cure among the residents in asylums,
whereas it is nearly as high as in the outside population. The time
elapsing between the onset of definite symptoms and the fatal termination
varies considerably according to tlie form of the disease and the resistance
of the individual. Is the institutional life more unfavourable than the
home life of the patient? I think not in the case of pauper patients, as
the food is wliolesome, plentiful and nutritious in the asylums; the
patients spend a considerable time in the open air, and, although large
numbers are collected in day rooms and wards, the air is infinitely better,
both as regards purity and temperature, than in the majority of the
overcro'vi^ded, badly ventilated and badly drained homes of the London
poor. These conditions, together with warm clothing and medical
attention, should to some extent counterbalance the effects of the mental
disease in making a comparison of the average duration of life after
active pulmonary phthisis has been diagnosed. It is impossible to make
comparisons with the pauper sane classes, about which there are no corre¬
sponding post-mortem data, nor with the cases attending a hospital for
consumption, e.q.^ the Brompton Hospital. We have no definite facts
to determine what is the average duration of the disease in a similar
class of the sane population, but it is probable that the Director of the
Henry Phipps' Institution at Philadelphia is right wlien he asserts:
“ The correct duration of the disease, however, should be measured from
the implantation, and this implies a long period of dormancy in most
cases. The probabilities are that tuberculosis is always primarily a
lymphatic disease, and that the 13 'mphatic period is alwaj’s dormant,
except when the disease manifests itself by an enlarged superticial gland."
The report further expresses the view that in the past medical men have
usually measured the duration of the disease hr the period of mixed
infections. The active destruction and ulceration with cavitation is
largely due to associated septic organisms. Lunatics, especially those
subject to fits, loss of consciousness, dementia, or who have to be fed

I'UUKKCtLOSlS li\* LU-NDOiN COLM’V ASYLUMS lOl

by a nasal tube, are especially liable to broiicbo-pneumonia owing to tluid
nourishment entering the bronchial passages. Such a condition in a
patient with obsolescent tubercle would light up the disease again, or if
there were no previous tubercular infection, form a very favourable soil
for infection from without. Thus we often find calcareous bronchial
glands or an old cicatrix at the apex in a lung in which there is active
broncho-pneumonic phthisis due to a mixed infection.

Occasionally I have found calcareous mesenteric glands, and, in an
autopsy I made at Colney Hatch Asylum on an imbecile youth, I found
an acute tubercular pleurisy which I ascertained was due to infection
through the diaphragm by a broken dow n mesenteric gland w^hich had
formed an abscess. The other mesenteric glands were caseous and
calcareous throughout. There could be no doubt that, although the boy
was not suspected of having phthisis on admission, he did not develop
this tubercular mesenteric affection during his residence of less than two
years in the asylum. Probably the infection occurred in early childhood
and spontaneous cure had occurred.

I liave made necropsies on patients wlio have died from active tuber¬
culosis, and the notes in the case book have decidedly pointed to the
acquirement of the disease since admission, yet careful i)od-moriem
examination has shown the existence of old lesions, that must certainly
have been present long before the patient was admitted. Occasionally,
but rarely, I have made autopsies in which I could find no evidence of
old tubercular lesion in the way of glands or cicatrices, yet I have
discovered that tlie physical signs on admission pointed to one apex being
affected, or I have occasionally ascertained from friends that the patient
had attended a liospital for consumption. In sqch instances there has
been a breaking down ulceration and cavitation destroying the original
quiescent focus of disease.

Auociation with mental condition ,—As there are no certain data forth¬
coming upon which to make statistics in regard to the mental condition
of the tuberculous insane, it w'as necessary to divide the forms of mental
disease into the following groups: —

Table XVII.

Showing the mental condition of the cases dying wnth active phtliisis during the ten

years. 1-9-98 to 31-8-08.

Form of Insanity.

MaU*s

Females.

Total.

Epileptic insanity

.*>

9

14

Epileptic imbecility

4

4

Imbecility and idiocy

9

14

Genc^ral |)aralysis

r»o

!

93

Melancholia

i

149

Other forms of insanity

> 73

110

Totals .

•201

213

•41b

Table XVllI.

Sliowing percentage of total autopsies with active phthisis during the ten years, 1-9-98 to 31-8-08, in which the disease w-as sufficiently
advanced to be the j)riniary cause of death. Comparison of various mental conditions.

N

Epilef)tics, imbeciles, and idiots lo 3 18 i 83 3 14 — 14 I l(K) 0 I -JO i 3 3*2 9(rti

TUliEiiCULOSlS iiN LONDUxN CUtxNTY AiiiLUMJi iOH

It will be observed that idiots and imbeciles are relatively few in
number, but they are for the most part not admitted to the London
County Asylums, but are sent to the Asylums of the Metropolitan Asylums
Board, lliese cases, therefore, may be practically left out of account,
although it may be remarked that the relatively few cases of imbecility
and idiocy which are admitted are especially prone to die of tuberculosis.
More of tliis class, especially boys, are admitted to Colney Hatch Asylum,
and when I made tlie autopsies there I noticed that death frain tuber¬
culosis was very common, and this accords with experience elsewhere.

I am indebted to l)r. Elkins for the following figures from Leavesden
Asylum. During the five years (1-1-Ud to b9d deaths occurred,

necropsies were made in G57 instances (95 per cent.), and 208 cases had
active phthisis at death. This latter figure includes the few cases of
tuberculosis which did not come to autopsy. Hence the percentage of
cases dying with active phthisis at Leavesden was 30 per cent. Dr.
Elkins has been very interested in the subject of tuberculosis, and has
done valuable work in connection therewith; he has made a special
effort to ascertain the existence of tubercle during life and post mortem^
consequently it may be assumed that this figure represents accurately
tlie proportion of deaths with active tuberculosis. It is therefore com¬
parable with the Claybury figures. It will be observed that the propor¬
tion of Leavesden to Claybury is 3 to 2; it might be asserted that this
is due to the fact that we are comparing an old asylum with a new
asylum, but it has been shown that the old London County Asylums—
Hanwell, Colney Hatch—have certainly not a higher incidence than
Claybury—a relatively new* asylum. The increased death-rate with
active tuberculosis must therefore be associated with the class of patient
at Leavesden, and the fact that imbeciles, idiots, and incurable cases of
insanity, which make up the bulk of the population of Leavesden Asylum
and the other institutions under the Metropolitan Asylums Board, should
die so frequently with signs of active phthisis accords with our experience
and with the statistics of the Prussian Blue Books.

The remainder of the cases may be grouped into paralytics and non-
paralytics ; the diagnosis of the form of mental disease in the latter was
symptomatic and does not therefore permit of systematic classification,
yet the large number of cases diagnosed as melancholia clearly indicates
a marked association of mental depression and tuberculosis. If we adopt
Kraepelin’s classification and only include under melancholia involu¬
tional forms of mental depression, then clearly the cases of melancholia
would be comparatively much less numerous. As mentioned on page 79
it is the insanity beginning in adolescence (dementia praecox) which is
so frequently associated with tubercle, and it is quite probable that in

U)4

AKCHIVES

tlie.se piitieuts tlie seeds of tubercle had not been sown on admission to the
asylum; as the mental symptoms progress the liability to infection
increases, but does this necessarily imply that they would be more likely
to perish from tubercle or perish in a shorter time if they were brought
to an asylum than if they remained at home. If tubercle is the infective
disease that it is believed to be by many authorities then tlie bringing
of feeble-minded into asylums and keeping them there till they die
should be a potent influence in diminishing the spread of tuberculosis as
well as of insanity, not, I believe, so much by removing a source of
infection by tubercular micro-organisms, althougli it would so operate,
but by preventing such weeds propagating their like, and transmitting
to future generations mentally and physically unsound stocks which
would infect healthy stocks. Segregation of the feeble-minded in colonies
and institutions before they have arrived at the reproductive period
of life would in the end turn out a national economic as well as a liygienic
measure, and would diminish pauperism, crime, insanity, and tuber¬
culosis. We know that prostitutes in our large cities are nearly always
sterile from venereal disease; otlierwise it would be positively appalling
to think of the number of illegitimate children defective in mind and
body that the State would have to maintain if in large towns women who
led immoral lives had numerous children, as so frequently happens in
country villages.

Occupation .—I have a.scertained the occupation of the patients dying
witli active phthisis at Claybury during the past ton y(‘ars: —

.M AI.KS.

Lahoiirers . ..

Fish Poilei’s ... •>

(derks . IH

(^oal Porters ...

Car|H‘nters . . . 11

(■oaciinien .. a

8oldi(‘rs ... .. 7

Shoemakers ... d

Painters ... .. 1

Grocers ... '1

Phinihei's ... .. d

J’ol icemen 2

Engineers . 1

Hawkers . ... 2

Sailors ... -1

(\)ok.s ... .. 2

Upholsterers .

Tailors 2

Printers ... ...

French J’olishers 2

Railway Portfis
Hatters
Errand Hoys
JInstrument ^lakers
Unknown
No oceiipatioii

Total

.)

o

10

('Tlie reiiiainiiJt*' M

casL's had each (littereiit occu)iati«»iis.;

These figures do not show much regarding the influence of occupation
on Ihe incidence of phthisis, as in a pauper asylum one would expect the
main proportion of the patients to be of the labouring and poorer class.

1 riJEK(;LLOSl.S IN LONDON COUNTY ASYLUMS

lo5

The females, however, show more interesting figures: —

F KM ALES.

Housewives ... 17

Servants ...

Charwomen
Needlewomen
Housekeeper.s
Dressmakers
Cooks

La undry maids . o

Hawkers ...

Nurses ... ... o

M aehinists '•)

Fur Haiuls 2

Bootmakers . 2

Bookfolders . 2

Bru.sh Workers

•)

Factory Hands

2

Barmaids

2

L’liknowii

4.

No occiijiation

58

Total

.. 201

17

()

<)

(Tlie i-eniaininu: 1-1 eases had each different oeeu])ations.)

It will be observed that more than 25 per cent, of the cases occurred
among women who were registered as of no occupation.* As the great
majority of these women are of the pauper class and must do some work
or have some occupation in order to obtain the necessities of life, and
bearing in mind what was said concerning the female general paralytic,
it seems highly probable that a considerable number of them may belong
to the unfortunate class that are obliged to obtain their living by pros¬
titution. A number of feeble-minded females, either by choice or
necessity (often both causes combined), take to tliis mode of living, and in
them all the conditions are favourable for the development of tuber¬
culosis. A certain number of young women who break down mentally
in the early period of adolescence or w^ho are feeble-minded from birth,
and have always lived at home without any occupation, form a part, but
I think it is probable t)»e smaller part, of this 25 per cent, of tul erculous
women w ith no occupation.

III.— Prophylaxis.

Since .Koch, at the Tuberculosis Congress held in London in 1901,
artirmed that the main cause for tuberculosis was its communicability
from diseased to healthy persons by the expectoration containing the
tubercle bacilli, there has been a widespread movement in all civilised
countries to combat the spread of the disease by this means.

Tlie death-rate from tuberculosis in England, however, had shown a
remarkable decline before science even had discovered the cause of the
disease. Professor Brouardel, in his address at the same Congress, said:
“ You have diminished mortality in England from tuberculosis by 40 per
cent.,” and he attributed this decline to the numerous Acts of Parliament

♦The large number of women in London that earn their living by prostitution are largely
the victims of venereal disease and are for the most part the subjects of alcoholism. All thest*
conditions tend to lower the vital resistance against tubercular infection. I do not find tlie
occupation of prostitute mentioned in the official asylum records, yet there must be a greac
number of such women admitted to the asylums.

AHCHiVES

lOG

and measures promoted by private individuals to render more salubrious
the dwellings of the poor and the conditions under which they live and
carry on their occupations in factories, mines and workshops throughout
the kingdom: —

“ Unhealthy dwellings cause other disasters. Dark and crowded as they
are, cleanliness is difficult, if not impossible, to preserve; they are not pleasant
t<j pass their time in, and the workman stays in his home as little as possible;
he eats there and sleeps there, but the rest of his time is spent in the public-
house. J. Simon was right in saying the wretched lodging is the purveyor of
tile public-house, and we can add to it that the public-house is the purveyor
of tuberculosis. In fact alcoholism is a most potent factor in the production
of tuljerculosis.”

Sot only does alcohol 6e lower resistance, but it is the most fruitful
cause of pauperism and all its attendant evils of unhealthy, overcrowded
dwellings with insufficient air and light; moreover, money expended by
the poor in drink means usually insufficiency of nutritious food, thus a
combination of devitalising conditions are brought about which favour
both soil and seed in the development of tuberculosis. It has already
been remarked that it is a general opinion founded upon statistics that
the high death-rate from tuberculosis among the insane as compared
with the outside public was in great measure due to the asylums and not
the patients—^in fact, that a large proportion of the cases of tuberculosis
are therefore preventable. If this be so it is our bounden duty to adopt
all necessary prophylactic measures (having due regard to economy) to
diminish this death-rate from preventable causes.

In all measures which may be adopted outside of asylums for the
prevention of tuberculosis it is necessary to remember that tuberculosis
is not an infectious disease in the sense of diphtheria, scarlet fever,
measles, typhoid; indeed, it is probably not so infecHous as pneumonia,
and it is well to take heed to the warning of Sir Hugh Beevor, who has
made a special study of this subject especially in relation to rural
phthisis. He drew attention to the remarkable constancy which obtained
year by year in the death-rate from pulmonary tuberculosis in the rural
districts of Norfolk, where the occupation and population (at ages from
25 to 45) had remained stationary for 30 years.

He further states: —

“ No, w'e must i)rocced in the interests of all by education and attention to
the wants of the people in food and in air, and we shall see the successes of
the past excelled by the higher successes of tlie future. I earnestly hope that
the medical profession at large will not encourage the public to avoid their
tuberculous fellow creatures. Such a course will not, in my opinion, diminish
the amount of tubercle. It will, however, infallibly .swell the ranks of the
unemployed, it will depress the phthisical wage-earner’s spirits, it will

Tl'BEKCULOSlS IN LONDON COUNTY ASYLUMS

1U7

(‘iiipty his ]»<»ckets, and ullimalvly, by want and (listit‘ss, reduce his fjiinily to
that coiulition of low vitality which the tiibeirle bacillus requires for a
successful invasion.”

Dr. Haldane inf onus nie of a fact which is also of iiuportance in show¬
ing that the soil is eveii more important than the seed. Investigation in
which he w as recently engaged on behalf of the Home Office show ed that
among Cornish miners at and beyond middle life the death-rate from
tubercular phthisis is enormously increased in consequence of the stone
dust which they have inhaled during many years of work. Although
nearly all these men die at home, and with every chance of spreading
infection, the local deatli registers show' no excess of death among the
w'ives and children of miners, and tlie death-rate from phthisis among
young miners is exceptionally low'.

Dr. Bulstrode, in his valuable report, comes to the following conclu¬
sions : “ The facts here set forth may perhaps be regarded as pointing to
the conclusion tluit tuberculosis is not a disease which can be reasonably
grouped as regards personal infectiousness wdth the acute exanthemata
such as smallpox and typhus fever; and this position, if accepted, should
involve a material difference in administrative action. Tuberculosis may,
perhaps, be best view'ed as occupying a distinct and separate position from
the exanthemata, and, as regards its duration and. low- degree of infec-
tivity, meriting a class to itself.^’

Practically speaking, there are two portals of entry of the specific
organism, viz., the respiratory tract (possibly tlie tonsils) and the intestirud
tract, and in respect to this important question it is desirable to refer
again to Koch’s memorable address, w hen he affirmed that the bacillus of
human tuberculosis w'as incapable of producing tuberculosis in bovines,
and that bovine tuberculosis w^as practically incapable of being trans¬
mitted to man; therefore the danger of contracting phthisis from the
meat or milk of tuberculous cattle need not be guarded against. This
dictum of Koch was not accepted by the majority of authorities on the
subject. It is now generally admitted that there is a practical identity
of human and bovine tuberculosis. Koch states his views thus: “ In by
far the majority of cases of tuberculosis the disease has its seat in the
lungs and has also begun there; from this fact it is justly concluded that
the germs of the disease must have got into the lungs by inhalation. We
know w'ith certainty that they get into the air with the sputum of con¬
sumptive patients; the sputum of consumptive people, then, is to be
regarded as the main source of the infection of tuberculosis.” On this
point he says, “ I suppose we are all agreed.”

AKCHIVES

lU8

Sir AVilliam Wbitla, in liis admirable Cavendisb lectures, adverting
to tbis statement of Kocb, says: —

“Many facts, some of them of rather a startling nature, have been brought
to light since the above words were printed a few years ago, and though it is
no part of my present purpose to attempt to prove that phthisis may not
sometimes be produced in this manner, it shall be my endeavour to show that
the results of recent experiment should induce us to conclude that the ink*stinal
route plays a far more important role in the production of human pulmonary
tuberculosis than has been hitherto recognised.”

In support of this view Sir William Whitla refers to tlie results of a
number of recent investigations as well as those which he conducted in
conjunction with Professor Symmers, and he states: —

“ These observers, liowever, reject Voii Behring's attirmatioii that adult
phthisis is always the result of an intestinal infection contracted in infancy,
since their experiments have demonstrated how easily and simply in¬
testinal absorption causes pulmonary tuberculosis in adult animals. Then
step by step the statements regarding the specific differences between the
human and bovine bacillus, and those made about the impossibility of
infecting boviiios with human tubercle, as well as the erroneous views regarding
the part played by inhalation, have binui disproved and the way finally opened
uj) for a clear appreciation of the intestinal origin of human phthisis througli
the demonstration afforded by experimental researches carried out on the
lower animals.”

As there can be no doubt that experiment and observation have indu>
bitably proved that the milk of infected cows can produce tubercular
infection of the human subject; and seeing that there is a widespread
occurrence of the disease in bovines from which we derive our milk
supply and a considerable proportion of meat consumed, it is obvious
that one of the most important steps to be taken in regard to prophylaxis
is to stamp out the disease in these animals or to adopt such measures
as may ensure the public against infection from this source. It has been
already said that there are two main portals of entry—the lungs and
the intestines; and practically it may be said that there are two sources
of infection: (1) By inhalation (a) of dried dust containing the tubercle
bacilli mainly derived from the expectoration of patients in the second
and third stages of pulmonary phthisis; {h) by the inhalation of particles
of moisture containing the bacilli expelled from tlie respiratory passages
of tuberculous patients, especially upon coughing. (2) The bacillus may
enter the body with the food and, since experiment has shown that it is
jiot necessarily destroyed by the gastric juice, it can enter the body by
die intestine and leave no signs there of its passage into the lymphatic
systom; the bacilli coming from the milk or butter, or uncooked flesh of

TITBERCULOSIS IN LONDON COI NTY ASYLUMS

109

infected animals, can produce primary tuberculosis in the lungs. Sir Wm.
W bitla remarks : —

“ That dosage is everything in the consideration of phthisis. Probably a
very small proportion of those infected by the bacillus of tubercle develop ilio
clinical symptoms of the disease, and it is here that the natural resistance
as manifested in the form of heredity comes into consideration; when the dose
Is large probably no human can escape . . .

“ The number of tubercle bacilli discharged daily in the sputum of a
patient in advanced phthisis has been said to be as great as the number of
human beings on the earth. The modest estimate Jiientioned by Cornet may
be taken as nearer the truth, viz., that 7,2UO,UOO,OUO may be daily thrown off
in the sputum from a single individual.

“ Even when we consider that a large proportion of these bacilli are dead
the numbers are so colossal as to defy realisation, and we must be driven to
the conclusion that the bacillus of tubercle is ubiquitous. Every individual
draws it into his ujiper air passages in the form of dust, swallows it in milk,
and probably injects it in infinitesimal amounts in almost every form of food
which has been long exposed to the city atmosphere. Were there not some
pow'erful phagtK’ytic and other mechanism for dealing with these minute do>es
of the tul)ertTe bacillus within the human healthy body, there probably would
be few, if any, of us left to study or discuss the tuberculosis problem.”

There can be no doubt that, although the tubercle bacillus is ubiquitous,
and likely in spite of all prophylactic measures to remain so, yet that if
dosage is of such importance in the production of the disease, theu all
measures which tend to diminish tlie number of tubercle bacilli which
the asylum inmates must perforce take into the body, either by inhalation
or by ingestion with food, will certainly tend to reduce the death rate
liom that disease iu asylums.

We havo seen that in successive years following notification an
increasing number of tuberculous cases were discovered, and in the
majority of instances segregated. This would tend undoubtedly to a
diminution of the dosage of the inmates who were healthy or free from
active disease. In this respect notification therefore has been a prophy¬
lactic measure of importance.

It might be asserted that there is no certain evidence that dosage
plays any part in the question of incidence of tuberculosis in attendants
and officials in lunatic asylums. But even if this be admitted, which is
doubtful, comparisons cannot be drawn between the relative effects of
dosage upon people healthy in mind and body and the insane inmates
who for the most part are physically feeble and of low vital resistance.
Consequently, if we admit the principle of the dependence of infection
upon the daily dosage, the most important prophylactic measure resolves
itself into the question of early diagnosis of active pulmonary phthisis
11 nd how it may be successfully attained. On p. 80 we have seen that
a large proportion of the cast's (25 per cent.) are not diagnosed during life.

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Whether the portal of entry be either the lungs or intestines, there
can be no question that a high percentage of unrecognised tuberculous
patients with active disease must cause a sowing of the seeds broadcast;
and the most important prophylactic measure to reduce the relative
amount of dosage of bacilli rests with the medical officers of asylums,
who by systematic examination of suspected patients would diminish
greatly the liability to large dosage by the early recognition of active
disease and by adopting the necessary prophylactic measures.

The first stage is the most important, for it is then intervention is of
real use; again, by curing the tuberculosis there is hope of curing the
mental affection; for the same cause may be at the root of each affection
and reciprocal interaction of the mental disease and the tuberculosis
tends to the production of a vicious circle, whicli can only end in death.
*The frequency with which one meets with tubercular ulceration of the
intestines is due to the fact that the insane swallow their expectoration;
of course, this tends to destroy any hope of recovery, and I think every
endeavour should be made on the part of attendants and nurses to
encourage patients to spit into properly provided recejitacles, even though
it may cause the nurses and attendants trouble to destroy the contents and
cleanse the vessels daily.

It is probable the air in the wards and dormitories of the London
County Asylums is not more contaminated by tuberculous organisms than
the homes of the people who are the inmates. Some years ago, when
Dr. Durham and I were investigating dysentery. Dr. Durham took some
of the dust of a ventilator flue of one of the large day rooms, and
inoculated a guinea pig without any result. A single experiment is of
little value, and I should have liked to have made an extended series of
observations ujion this important question; but, although there are
hundreds of guinea pigs kept for the amusement of the patients, my
laboratory not being licensed, I am unable to utilise these for purposes
which might be of much more use to the unfortunate inmates.

I am inclined to think that there is a greater danger of conveyance
of tubercle bacilli from an infected individual to a non-infectecl individual
by th.e fine particles of moisture expelled in coughing than by the dust
of dried sputum. I have not observed much evidence of patients spitting
on the floors when I have visited the day rooms and dormitories of the
London County Asylums. As regards personal cleanliness the inmates
of asylums are frequently defective in their habits, and their clothes are
often soiled by fcecal matter; but apm‘t from the fact that there is

♦The tubercle bacilli were fcuud by Dr. ('andler in the stools of a patient who was
supposed to be sufferin^iwith dysentery, and lie is at ])resent enpaircd in a research with the view
of ascertaining if the examination of the stools of donhtful tiilx'i culous eases would affoi'd an
additional means of diagnosis.

TUBERCULOSIS IN LONDON COUNTY ASYLUMS

111

the disadvantage of large numbers collected together, the personal
cleanliness and hygienic conditions are of a higher standard than the
generality have been accustomed to. Moreover, the quantity and quality
of the food is better than the majority of people of the same class obtain
outside the asylum.

Nevertheless, in my view, the facts and statistics tend to show that
active tuberculosis runs a more rapid course in the insane than the sane,
and this is mainly owing to an inherent low vital resistance and the greater
danger of auto-infection and associated invasion by seiAic and pyogenic
organisms^

Various prophylactic measures have been adopted at all the London
County Asylums to prevent infection and to improve the vital resistance
of tuberculous patients. The following summary of the precautions
adopted has been prepared from the information kindly supplied by the
superintendents of the various asylums: —

Re milk supply ,—All cows are submitted to the tuberculin test and
sent back to the vendor if they are found to react. In many asylums it
is apparently the custom to apply the test periodically. The risk of infec¬
tion from tuberculous milk is greatly diminished in the case of the in¬
mates of the London County Asylums as compared with the outside
population, for whereas in the former case the milk supply is carefully
superintended, in the latter case, according to the Medical Officer of
Health for the City of London, ‘‘ practically no precautions are taken by
either the farmers or the w holesale dealers in London to ensure that the
milk for which they are responsible is not a vehicle for the conveyance of
tuberculosis.^' This is evidenced by the fact that during the first three
months’ inspection of milk samples (July—September, 1908) by the
London County Council per cent, were found to be tuberculous, and
from the follow ing October to January, 285 samples were examined and
7*7 per cent, were found to be tuberculous.

It would be interesting to know what percentage of the samples of
butter sold in London contained tubercle bacilli, as this is a staple article
of food, especially for the poorer classes, and, as the greater part of the
quantity consumed is not subiocted to any process of cooking, it may be
a fruitful source of infection.

Dr. Moody states, referring to the tests: —

“ These may or may not be of value, but 1 can say that before the test was
applied before purchase, we often had found iho carcases on slaughter so
tul)erculous that they were condemned as unfit for food, whereas this is now
quite the exception.”

At Colncy Hatch Asylum the tuberculin tost is now^ not applied, but the

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milk is submitted to the Councirs chemist for examination. Milk from
the farm is sterilised.

Re therapy, diet, and sanitation: —There is apparently no routine
therapy or dietary for tuberculous patients. Each case is individually
catered for with such extras of milk, beef tea, dripping fat, cod liver
oil and malt, creosote, etc., as may be indicated. The possibility of the
entrance of tuberculous organisms into the body by butter made from the
milk of tuberculous cows does not arise, as margarine is used as a
substitute.

The ordinary methods of sanitation are practised. Spitting cups are
washed out frequently with disinfectants, sputum is wiped up from the
floors with rags, which are immediately burnt. The side rooms inhabited
by tuberculous patients are disinfected, and at one asylum Sanitas lamps
are burnt in the phthisical wards.

Re isolation. —All diagnosed tuberculous cases are isolated as far as
tlie mental condition of tlm patient and the construction of tlie asylum
will allow: —

Banstead Asylum :—

“ Male cases cf>]lcct(‘(l in Ward 8, a detached hnnc;al<>w ; females, in one
special ward.”

Beocley Asylum :—

‘‘All patients suffering from tuberculosis are collecte<l together and. a.s far
as possible, are isolated, the males in tlie East Villa and the females in H 1
ward {vide Plate I.). They are given open-air treatment, and if the patients
are confined to bed, the beds are placed in verandahs.”

(Jane Hill Asylum :—

“Our tulierculous patients, with few exceptions, are placed in J 1 and
J 2 wards, female division, and G 2 ward, male division, to which large
verandahs have been attached on my recommendation. Tn these wards we are
able to treat the patients largely in the open-air with decidedly beneficial results ”

Clayhui'y Asylum :—

The tuberculous cases are collected, as far as the mental condition will
allow, in special wards.”

Colney Hatch Asyluruj :—

“ All tuberculous patients on the female side of the Asylum are at present
collected in Ward E8; they will shortly be removed to the new infirmary (vide
Plate II.) for tuberculous cases, which is provided with verandahs. On the male
side the greater number of the tuberculous patients are collected in Ward C 5,
and it is in contemplation to provide a verandah in connection with it. The
remainder of the cases are kept in single rooms.”

Hanwell Asylum :—

“Unfortunately w’c havt‘ no means here of carrying out absolutely the
isolation of tulnM-culous pati^^nts. As far as i)ossible we place all such patients
in single rooms, but owing to the necessarily imperfect ventilation of these

TrUKRCULOSlS IN LONDON COUNTY ASYLUMS

113

rooms (clue largely to their size and the absence of fireplaces) I am in consider¬
able doubt as to tlie wisdom of this proceeding. We have no special means of
carrying out the open air treatment. iSuch tuberculous patients whose mental
and physical condition will allow are warded in infirmary wards, from which
there is easy access to a court, and they are permitted to spend practically the
whole day out in this court when the weather is favourable.”

Horton Asylum :—

“ All patients showing active signs of tuberculosis are housed chiefly in
infirmary A on the female side, and infirmary I on the male side. Attached
to these two wards are large verandahs where treatment, as far as possible, is
undertaken in the open air (ri</c Plate III.). A few of the more excited ones,
however, have at times to be kept in infirmary B on the female side, and
infirmary 2 on the male side.”

Lcnuj Grove As^ylum: —

“ All tuberculous patients aiv i.solated in one ward on each side of the
building. This ward has two dormitories and a number of single rooms
besides the usual day-room and dining room. All the active cases of tubercle
are placed in one of these dormitories; certain of them whose habits of spitting
are very marked or for other special reasons, are placed in single rooms.
Practically all of these cast s who are not up and about si^end the whole of
each day from either before or just after breakfast until sunset in beds under
a wide glass verandah built out along one side of this particular dormitory,
and other tubercular cas^‘s sit there and also have the use of the garden.”

Horton Manor Asylum :—

“Tuberculous cases are collected together, as far as possible, in special wards.”

The Epileptic Colony :—

“ Very few cases of tubercle occur ; they are treate<l in the Infirmary Villa,
the verandah of which is suitable for open-air treatment in the daytime.”

It will be observed that at all tlie asylums isolation of patients suffering
with active tuberculosis is practised as far as the mental condition of the
patient and the construction of the asylum will allow. At Colney Hatch
a special isolation hospital for tuberculous patients (Plate II.) is in con¬
struction, and it will be interesting to see in the future how far the
incidence of active tuberculosis diminishes in that asylum and how far
that institution will compare favourably wdth another old asylum like
Hanwell, in which there is no special provision for isolation or open-air
treatment. The admirable verandah arrangements at Bexley, Horton,
Long Grove, and Cane Hill, to my mind, are economical and fulfil all the
purposes required.

The great decline in the tuberculosis death-rate among the outside
population which has taken place during the last 30 years is undoubtedly
due to the improvement of the general social conditions of the people,
e.g., the better housing of the poor, the improvement in the conditions
of light and ventilation in workshop and factory, combined with cheaper

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food and the fall in the drink-bill. Doubtless the death-rate from this
disease will steadily go on falling for the same reason that every year
sees a progressive improvement in the social conditions of the mass of the
people ; and a steady fall in the death-rate from the time tuberculosis is
regarded as an infectious disease and made notifiable, may be ascribed
wholly but erroneously to the great diminution of dosage—that is, the
dissemination of the seed—by this special measure. But if tuberculosis is
to be a notifiable disease, why not syphilis!^ Certainly, the evidence of
conveyance of the disease from one individual to another by contact and
cohabitation is very weak in the former as compared with the latter.

The more phthisis can be treated in the early curable state the less
will be the chance of there being a focus of discharge of tuberculous
organisms.

This is a matter of diagnosis, and it might be desirable lo adopt in our
asylums even more systematic attempts to discover early cases on admis¬
sion, or shortly after admission, for it appears to me this is the very
essence of the question of prophylaxis.

Summary.

1. The evidence adduced does not support the contention that infec¬
tion is one of the strongest causative elements in the prevalence of tuber¬
culosis in tlie London County Asylums ; still less does it support the view
tliat the causes of tuberculosis inhere in the x\sylums themselves and not
in the character of the patients sent to them.

2. Notification during five years from all the London County Asylums
does not show any ward incidence comparable with that showm by the
notification of dysentery during the same period ; therefore if tuberculosis
is communicable, it cannot be regarded as an infectious disease in the
same sense as dysentery, small pox, scarlet fever, etc.

3. The average proportion of living patienis reported as tuberculous
is 20 per 1,000 inmates of the Londo-n County Asylums, but the incidence
of reported cases shows very considerable variations, the lowest being
Cane Hill, 10 0, and the highest Claybury, 40 3. The personal equation
must largely contribute to these wide differences.

4. Association with mental disease of the cases reported during life
indicates that young subjects suffering from melancliolia, dementia
]u*8ecox, and imbecility are especially prone to the disease.

5. Post-mortem statistics confirm this correlation, but in addition
show that a large number of general paralytics die with recent active
tuberculosis which is not diagnosed during life ; this is especially the
case in regard to female general paralytics, for which fact reasons are
given.

TL'HEUcrLUSlS IN LONDON COlNTY ASYLUMS llO

6 . In 14*8 per cent, of the autopsies made at the London County
Asylums during the past five years, active phthisis was found. Again, a
great variation in the returns from the various Asylums was noticeable,
for which the personal equation must be held largely responsible.

7. It cannot be shown that the variation in the incidence of tuber¬
culosis in the various London County Asylums depends in any measure
upon the class of patient received, the parish areas from which they are
drawn, the construction and age of the Asylum, or the dietary or treat¬
ment. Cane Hill Asylum, situated on a high chalk down, has a com¬
paratively lower death-rate and a lower tuberculosis death-rate than any
of the other London County Asylums. The relatively higher death-rate
from tuberculosis at Claybury may be explained to some extent by the
fact that the necropsies are made by a skilled pathologist, but it might
be attributed to the clay soil and cold damp climatic conditions, althi>ugh
the total death-rate is lower than at most of the other Asylums.

8 . A comparison of the phthisis death-rate for 1907 at the several
age periods per sane living in London, and per 1,000 of the total living
insane population (18,872) resident in the London County Asylums show
that the mortality from phthisis among the insane is highest at a much
earlier age period than among the sane. Ay the age period 45-55, when
i^ reaches its maximum among the sane, it is a question whether the
incidence among the insane is much greater than among the sane pauper
population.

9. The comparison also shows that the death-rate from phthisis for
the insane between the ages of 15-d5 is about 15 times that for the sane
for the same age period. Allowance, however, must be made for the fact
that the majority of the inmat(‘s of the Asylums belong to the poorest
classes.

10. The Jewish pojmlation at Colney Hatch (mainly aliens) show a
higher death-rate (25*7 per cent, of total deatiis) from tuberculosis than
the Christians, for which fact reasons are given.

11. Evidence is not forthcoming to prove that the statf in the London
County Asylums contract tuberculosis from the patients.

12. During the past ten years 1,982 necropsies were made at Claybury
Asylum by skilled pathologists, and active phthisis was found in 410
cases (20*9 per cent.). Tuberculous ulceration of the intestines was found
in 73 males (36*3 per cent.) and 115 females (53'4 per cent.) of the cases
dying with active tuberculosis. Twenty-five per cent, of the deaths with
active phthisis occurred within one year of admission, and practically
70 per cent, within five years of admission.

13. The 'post-mortem statistics for the past six years show that 510
per cent, of all the patients dying exhibited either obsolescent or active

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tuberculosis or both. It was inferred from the jiost-mortein examination
that not more than 10 per cent, of the cases with active phthisis at autopsy
could have acquired the disease in the Asylum.

14. Infection with the disease depends upon dosage and resistance.

15. The prophylactic measures for the prevention of tuberculosis are
good in the London County Asylums as regards milk, food, personal
cleanliness, ventilation, clothing, warmth, and exercise in the open air,
and the liability to infection from preventable causes is less than in the
houses from which the majority of the insane are taken. The only fur¬
ther prophylactic measures consistent with proper and due economy
appear to be (1) the earlier and more frequent diagnosis of active phthisis
with a view to isolation and treatment, (2) the adoption of the verandah
system of open-air treatment at all the Asylums, and (3) the encourage¬
ment of patients suifering with phthisis to expectorate into proper recep¬
tacles and thus possibly diminish the amount of intestinal tuberculous
ulceration caused by autoinfection.

I am indebted to the medical superintendents of the various Asylums
•for much valuable information and the illustrations shown in Plates I.
and III.; also to Mr. Clifford Smith for the plans of the new hospital at
Colney Hatch (Plate II.).

In conclusion, I wish to thank Dr. Bulstrode for his valuable advice
and for kindly looking through this paper. Also I desire to acknowledge
the help I have received from his valuable reports for the Local Govern¬
ment Board, “ Sanatoria for Consumption and certain other Aspects of
the Tuberculosis Question.’’ Moreover, I wish to acknowledge the
invaluable aid I have received from my assistant, Mr. Sydney Mann, in
keeping the records for the past five years and preparing the statistics
therefrom.

I’LATK J.

Face p. lie.

H 1 Ward. Female Side, at Bexley Asylum, showin^^ verandali.s for open-air treatment of Tuberculosis,

Si .M^ E4r.Jfr ^>^E,T TO ONE

I’LATK II

GROUND FLOOR PLRN

117

EXAMINATION OF THE NERVOUS SYSTEM IN A CASE
OF CHRONIC LEAD ENCEPHALITIS.

By F. W. MOTT, M.D , F.R.S., F.R.C.P.

With Clinical Notes by Fredk. H. Stewart, M.D., Senior Assistant
Medical Officer, Kent County Asylum.

J. D., set. 41, married, coach-painter, said to be an epileptic, was
admitted under my care on November 18th, 1907.

Family history .—No insanity or alcoholism traceable. Father died
from pulmonary tuberculosis, set. 44. Mother alive, set. 79. Two brothers
and five sisters alive and apparently healthy. Paternal and maternal
grandmothers and grandfathers lived to an advanced age.

Personal history .—^Has been a painter since he was a boy. Never
acquired syphilis. Used to drink heavily at times. Is said to have been
treated for enlargement of the liver ’’ three years ago. Married about
10 years ago to a healthy young widow, 4-para. All her children likewise
healthy. She states that she never conceived by him, although she is now
still within the child-bearing age.

While at his work, painting a motor-car, early in July, 1907, he
suddenly became unconscious, owing to the onset of a convulsion,
described by a medical eye-witness, as epileptiform in type, and diag¬
nosed by him, as due to plumbism.

For some time previously he had suffered much from agonising colic
and obstinate constipation. He recovered from the convulsion, and was
able to resume his work in a few days. Then it was noticed that he broke
down at his work, time after time, and if he attempted to pull himself
together by alcoholic indulgence, even in very small quantities, it made
a fool of him.’’ His fellow-workmen noticed this, as previously he was
able to carry a decent “ load ” with apparent impunity. He was admitted
into a union infirmary on two later occasions, viz., August 14th and
September 2nd, 1907, treated there for alcoholism, and duly discharged
recovered.

Present illness .—Began by a somewhat sudden onset on November
18th, 1907. He was observed to have a wild appearance, incoherent
ideas, inability to give a reasonable account of himself, illusions of

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si^lit, wanted to eat his pillow, restless, habits unclean, difficulty in
swallowing, pulls his bed about, and looks under the clot lies very much.
He had not had any alcohol for three to four weeks previous to this date.

State on admission — General .—Very weak and tottery. Temperature,
99*8 F., weight 8 stone 7 lbs., height 5 ft. 9 ins.

Marked cachexia, face in lower third looked puffy {vide Fig. I.), pupils
dilated, equal, but eccentric.

Fig. 1.

Oral sejisis, breath very ott'ensive. An irregular blue line present in
gums. This remained after thorough cleansing with cylliii and tootli
brush. Two irregular slate-coloured patches also present in mucosa
lining lower lip. Palatine conformation rather high and narrow, with
tendency to irregularity.

Menlid condition .—Marked restlessness, appearance excited {vide
Fig. 1), general clouding of consciousness, disorientation, difficulty in

LEAD ENCEPHALITIS

119

comprelieusioii. Ideas confused; attention weakened, remitting delirious
states. Periods of shouting, apparently coincident with the paroxysms
of colic. Rather drowsy, but has short lucid intervals. At night he
becomes worse, being very sleepless and continually tries to get out of
bed. Is passively resistive, has auditory hallucinations, says he has
severe pains in the head, asks to be killed, craves for water, is in a state
of morbid fear.

Physical condition.—Deruhitiis dor.udisy with both thighs flexed on
abdomen and some flexing of trunk generally. Unable to stand alone,
hand grip and gait impaired. Bilateral drop-wrist, and extensor
paralysis of all the fingers; spills contents of his feeding cup on attempt¬
ing to lift it towards his mouth. Supinator longus not affected. The
reaction of degeneration is present in the paralysed muscles; there are
coarse tremors observable chiefly affecting the upper extremities, also
irregular fibrillary twitching of the same parts. Staccato articulation.

Sensory .—During the lucid periods no marked alteration could be
detected in common, thermic, or pain sensibilities. Stereognostic, vibra-
tile and muscular doubtful. He did not wince on deep pressure being
made on the paralysed muscles.

Reflexes .—The pupils are regular, equal, and of moderate size. They
react sluggishly to light and accommodation.

Cremasteric and epigastric diminished. Plantar extensor reflex not
obtained. The knee jerk is brisk, especially on the right side, ankle
clonus absent, elbow jerk exaggerated, jaw clonus easily elicited.

Organic .—Deglutition difficult, can only take liquid nourishment.
Respirations laboured (12 per min.). Micturition and defalcation at times
are not under control. Enuresis at times.

Trophic .—Tliere is marked wasting of muscles in all the interosseous
sjKices, also of the thenar and hypothenar eminences. Some thickening
and contraction of palm, the general voluntary musculature was atonic,
and fibrillar contractions were characteristic.

Vaso-motor .—Tache cerebrale well marked.

Fundus ocidi. —Xeuio-retinitis present, but unecjual in the two eyes.
Impairment of vision.

Ilearl .—Impulse beat in nij)ph‘ line, action increased, but varied with
exacerbations of colic. First sound in mitral area impure, no trans¬
mitted bruit. Second sound in aortic area accentuated, pulse variable
in rate, regular. Radial palpable. Pressure variable, high when colic
was severe. The majority of the arteries were thickened.

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Lungs ,'—Slight cough. No definite physical signs of disease.

Abdomen .—Slight retraction, rigidity, tenderness chiefly on right side
and above umbilicus. Testicular atrophy, loss of sensibility on pressure.

Urine, —Clear, acid, Sp. Gr. 1*011. Trace of albumen. Lead not
tested for.

Treatment amj Progress.

Owing to the difficulty in swallowing he was given only fluid nourish¬
ment from a feeding cup. It consisted of milk and albumen water in
amounts equal to J iv. three-hourly. I'he extreme thirst was also
allayed by enemata of 5 xx. normal saline solution almost daily. His
bowels were kept open daily with white mixture 3 ss. given at 7 a.m. I
occasionally varied this with confection of sulphur in 3 jss. doses. He was
also given a mixture containing potassium iodide, gr. v., thrice daily.
The colic and general restlessness were treated by warm baths of half an
hour’s duration morning and evening. At night a hypodermic of
morphine sulph., gr. was substituted when necessary.

November 18.—Night report: Two hours’ sleep, restless, noisy, con¬
tinually tries to get out of bed, auditory hallucinations acute, resistive,
very confused ideas, wet.

November 19.—Day: Drowsy, lies in bed better, very thirsty, wet and
dirty. Saline enema and baths given.

Night: Three hours’ sleep, similar to previous night, thirst. Tem¬
perature normal.

November 20.---Day: Colic severe, restless, veiy confused ideas,
thirst. Morphine gr. ^ hypod. llequires feeding with spoon. Warm
baths.

Night: One hour’s sleep, troublesome to keep in bed.

November 21.—Day: Taken three pints milk with difficulty, short
lucid intervals. I frequently conversed with him during tliese lucid
times, and his conversation was rational and well sustained. To my
mind the contrast to his usual condition was marked.

Night: No sleep. Morphine gr. hypod. Colic severe.

November 22.—Day: Similar to previous day.

Night: Weaker, no sleep, unable to get out of bed now, wet.

November 23.—Day: Very confused to-day, articulates with diffi¬
culty, soap and water enema at 11.30 a.m., motion light yellow in colour.
Tw^o pints of milk. Morphine gr.

Night: Slept from 8 p.m. till 3 a.m. Involuntary evacuations. Very
weak.

LEAD ENCEPHALITIS

121

November 24.—Day: Colic less severe, no mental improvement, un¬
able to help himself. Saline per rectum, one pint.

Night: Slept eight hours, quieter.

November 25.—Day: Sight noticed to be very bad, has much diffi¬
culty in swallowing even liquids, bowels relaxed, motions light yellow.

Night: Slept from 11 p.m. till 4 a.m. Respirations eight per minute.

November 26 and 27.—In padded room owing to falling about, from
general debility and tendency to injure himself. Tube fed for first
time.

November 28 and 29.—Unable to swallow now ; looks like the final
stage of general paralysis, emaciation, incoherent jargon. Much mental
reduction evident.

November 30.—Evidences of bronchitis present to-day. Saline enema
alone given. Very low.

December 1.—Died at 6.50 p.m.

Fost-mortem December 2nd, 1907, at 11 a.m. Room, temperature
52 F.

Very emaciated cadaver, with slight abrasions on forehead, nose and
knees.

Fost-mortem lividity and rigor mortis established.

Slight bruising on arms and chest. Small sores on legs and trunk.
Pupils dilated. Arcus on both corneae.

Scalp. —Small areas of ecchymosis present, thickjiess and attachment
normal.

Calvarium. —Nothing unusual.

Dura. —Dry appearance. Non-adherent.

Fia~Arachnoid. —Dry, glistening appearance, slight excess of fluid;
frost-like opacities along course of vessels over posterior two-thirds of
both hemispheres. Slight injection of vessels.

Brain. —As a whole firm, w eight 48^ ozs.

Ventricles. —Choroid, pale and cystic, no granulations evident.

Mouth. —Very septic. Septic bronchitis. A haemorrhage about the
size of a sixpence present at base of epiglottis and left vocal cord.

Lungs. —Some septic broncho-pneumonia in early stage, most marked
on right side.

Fericardium. — Small amount transudate fluid, epicardial “ milk
spots.”

Heart muscle. —Markedly striated, bluish colour. Weight of organ
11| ozs.

Ventricles. —Contracted, pale yellow formations right side, dark clot
and very slight hypertrophy left ventricle.

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Vdivis. —Cuiiipeteiit, a few areas of atlieroma at coronary orifices, and
also at allachineiits of mitral cusps.

- Jlealtliv in upper parts, atheroma near its bifurcation.

—All more or less thickened.

Peritoneum . — Uetroperitoneal hauuon hage in region outside tlie pan¬
creas. It was recent and of small amount, and had become diffuse in the
loose tissue of the mesentery. Mesenteric glands enlarged, indurated
and bluish on section. (Ksophagus healthy.

iSionidch .—Mncli nuieoiis present and about .S iv. bilious tluid. Mucosa
pinkish.

Stained with bile in upper parts, vessels congested, large
bowel constricted at irregular intervals.

-Contents semi-ffuid, and of an orange yellow tint.

Jejunum and iJeuni. — Contents darker.

(aecurn .—M ucosa si at e-coloured.

Polon. —Irregular constrictions, between which were large dark
greenish scybalous masses. Eectum empty.

7>/rcr.- -47'* ozs. llluish colour on S(‘ction, with pale yellow areas,
llile very dark, no calculi. Soft consistency, volume reduced.

Spleen. -Surface mottling, usual size and weight.

Kidnajs. —Little fat around each. Both cirrhotic, capsule adherent
to an atrophic granular cortex. Bale in colour. Eight dj ozs., left 4 ozs.
Pelves healthy, no calculi.

Bladder —Some turbid urine. Mucosa healthy.

Supra-reitfd . —Eight medulla cystic, cortex casc^ous. Left well
marked; differentiation between these two parts. }dedulla slate colour.

MuseJes .—Dark in colour. Wasted.

1. IIisToLociiCAL Examination.

Brain and spiufd eord. —Portions of tlie top of the ascending parietal
and frontal convolutions, top of first frontal and the cervical enlargement
of the spinal cord and medulla oblongata, were examined by Nissl, poly¬
chrome blue, polychrome blue and eosin, and Van Gieson methods for cell
changes. Sections of 6-7w were cut and stained by the above methods
after the tissues had been hardened in formalin, dehydrated in alcohol,
and embedded in paraffin. Portions of the ascending frontal and parietal,
cerebellum and the lumbar, dorsal and cervical regions of the spinal cord
were chromed, cut in celloidin, and stained by Weigert and Pal methods
to display fibre changes and sclerosis. An attempt was made to stain
by the Cajal silver method, but except for the display of the neuroglia

LEAD ENCEPHALITIS

123

cells it was unsuccessful owing to too prolonged action of the fornialiu.
The glia proliferation, however, is extremely well displayed {vide Fig (i,
Plate I., and Fig. 2).

The spinal cord was very much damaged in removal, and the sections
accordingly are for the most part unsatisfactory. The nerves were curled
up, and owing to imperfect methods of labelling could not be identified.

Cerchral cortex—Le pto-nieniticjcs. —The pia-araclinoid is thickened
somewhat; tliis thickening is due to fibro-blasts and fibres, there is no
infiltration with lymphocytes and plasma cells such as is always found
in g(‘neral paralysis. There is a hyaline thickening of the walls of the
vessels, both arteries and veins {vide Fig. 7, Plate 1.).

Fkc ' 2 .

Drawing uf a .section of tlie cortex, sliowing the iiyperpla.'-ia of tl»e neuroglia cells, stained hy
Ueideinhain liajinotoxylin ci.-in method. Magnification 750.

The cortical vessels and perivascular sheaths .—There is some congestion
of the vessels, but tin' perivascular sheaths of the pia-arachnoid show no
all in filtration with hjm [diori/tes and plasma cells. The walls of the vessels,
however, are thickened, and, owing to the congestion and cell prolifera¬
tion and hyaline degenerative thickening of the walls of the small vessels,
both caj)illaries, arteries and veins appear more distinct than in the
normal brain; moreover, many of the smallest vessels have ruptured,
causing miliary microscopic hieiuorrhages into the perivascular sheaths

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and into the substance of the brain. Adherent to the vessels are large
numbers of hranching hypertrophied glia cells {vide Fig. 6, Plate L, and
Fig. 2). Some vessels are affected by the hyaline degeneration more
than others.

The neuroglia, —The most striking feature about the microscopic
appearances of this cerebral cortex is the neuroglia hyperplasia. This
proliferation of the branching neuroglia cells is observed not only in the
superficies of the cortex, but also throughout the grey and white matter;
it is most marked in the superficial and deeper layers of the cortex and out
of proportion to the wasting of the neural elements; it appears, therefore,
to be a formative hyperplasia resulting from chronic irritation. Besides
this hyperplasia of the mesoglia cells there is an abundant proliferation
of young neuroglia cells consisting mainly of a nucleus containing a fine
chromatin network with a number of delicate nodal points with clear
hyaloplasm between. These are seen in little colonies, the result of active
proliferation, especially in the deeper structures of the cortex and white
matter. They are not in the sheaths of the vessels, but are often seen
in the perineuronal spaces. They can be followed in all stages up to the
formation of large branching glia cells sending their processes on to the
walls of the vessels, where they end in a sort of foot-like expansion.
There is a considerable amount of subpial felting indicating that the
glia proliferation of the molecular layer is of earlier origin than the
remainder of the glia proliferation.

The cells of the cortex, —The cells are arranged in columns, and all
the layers can be seen, although owing to degenerative changes in the
cells, to be presently described, and to a great proliferation of the
neuroglia nuclei, the regular arrangement of Meynert’s columns so
characteristic of a section of normal cortex is not so readily made out,
especially is there a neuroglia proliferation in the polymorph layer and the
molecular layer. Changes in the large Betz cells are most readily seen if
present, therefore these structures will be first considered. Some of these
cells are paler than natural owing to the fact that there is a more or less
considerable diminution of the Nissl substance; also the Ifissl pattern is
more or less lost and a fine dust of stained particles is seen instead of the
tigroid substance Fig. 2, Plato I.). Where this is present in the cell
it is mainly at the periphery; there is, indeed, a moderate degree of peri¬
nuclear chromatolysis in some of the cells such as one generally finds in
a case of chronic peripheral neuritis whether due to lead, alcohol or other
toxic agency {vide Fig. 4, Plate I.). The change is not nearly so pronounced
as I have seen in other cases. The dendritic processes in some cells appear
to be attenuated and not so well seen as in normal structures. Some of

LEAD ENCEPHALITIS

125

the cells show an accumulation of yellow pigment in one portion of the
cells, but, taken as a whole, these cells do not show marked changes
indicative of a profound paralysis of the lower limbs. Glia cells are
rarely seen in the perineuronal spaces of the Betz cells; whereas in the
subjacent polymorph layer and the superjacent pyramidal layers
abundance of neuroglia cells are seen apparently exercising phagocytic
functions. A ganglion cell is often seen with one or several neuroglia
cells glued to it, so that if the neuroglia cell is a large branching one, it
is difficult to make out how much of the cytoplasm belongs to the ganglion
cell and how much to the neuroglial cell. The impression one obtains is
that the neuroglial cells are devouring the ganglion cells.

The view was put forward by Bevan Lewis that the proliferating
glia cells “ become the ‘ phagocytes ’ or scavengers of the tissue ; live,
thrive, and multiply upon the degenerating protoplasmic masses of nerve
cells and their extensions; and all eftete material lying in their neigh¬
bourhood is ultimately appropriated to their use.^' Certainly appearances
in these sections tend to support this view. The polychrome-eosin stained
sections show this best, because the cytoplasm of the neuroglia cell is
stained pink. A striking object is the appearance of the neuroglia cells
which are undergoing hyperplasia. The nucleus in some of the cells can
be seen to have divided into as many as eight daughter nuclei. Again,
one sees the pink cytoplasm of the glial cell with branching processes, and
in the concavity of two branches a nucleus with only a thin layer of pink
cytoplasm around. These young neuroglia cells can be seen in numbers
around decaying or disintegrated pyramidal cells; and it appears in
places as if they had taken the place of the ganglion cell. But as I am
unable to see these glia cells in any section attacking degenerated large
pyramidal cells I am doxihtful how far one can go in asserting that the
appearances are conclusive as to their attacking and devouring the other
ganglion cells; for the appearances observed may all be due to proximity
of the glia cells undergoing proliferation to smaller and primarily
degenerated cells. One thing I can be certain of, and that is, there is no
polymorpho-nuclear phagocytosis and no leucocytic infiltration of the
tissues, and the products of the degenerated nerve cells have to be
removed in some way or other.

Fibres .—There is no gross atrophy or degeneration of the fibres of the
cortex. The tangential and supra-radial fibres are diminished in number,
but this is comparatively to general paralysis only slight. Neither the
cerebellum nor the spinal cord at any of the levels examined show any
fibre atrophy or degeneration except jmssihly a slight diffuse sclerosis in
the crossed pyramidal tracts of the lumbar region.

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Spinal cord and medulla. —The grey matter of the cervical enlarge-
meat shows numbers of hyemorrhages, but i am not sure from the appear¬
ance of the sections that this may not be due to artifacts. The ganglion
ceils of the anterior horn show chionic changes which cannot be associated
with this condition. There is a perinuclear chromatolysis of some of the
cells indicative of a neuritic condition [vide Fig. 1, Plate 1.}. The vessels of
the medulla and spinal cord show liyaline thickening and degeneration.
The vessels of the choroid plexus show this change in im es^iecially
marked manner. There is no evidence of granulation of the floor of the
fourth venticle, a change which is so especially characteristic of general
paralysis. There are some microscopic haemorrhages in the medulla, of
the ninth, tenth, eleventh, and twelfth nuclei. A large number of cells
of the medulla oblongata, small as well as large, show more or less and
in a variable degree some chronic degenerative changes. The processes
are broken olf, many of the large cells have more or less lost their
incurved outline and become more or less rounded; in many of them
the nucleus is eccentric, and in nearly all there is some diminution of
the jN'issl substance. This diminution in the majority of instances is
due to a iJcrinucUar chromatolysis. This is fairly well seen in a large
number of the cells of the vagus nucleus and glosso-pharyngeal nuclei
[vide Fig. 5, Plate 1.); likewise the nuclei of the funiculus gracilis, and
iUirdach’s column show chromolytic changes. The hypoglossal and sixth
neiwe nuclei do not show so much chromolytic change. A great many of
the cells show a marked excess of yellow pigment. Very few of the cells
are absolutely normal, but side by side may be seen grades of chronic
change. A few vessels may be seen with lymphocytes in the lymphatics
(not in the perivascular sheath) of the adventitia of the arteries. No
plasma cells, however, were seen. As compared with the cerebral cortex
and subjacent white matter the glia proliferation is very inconsiderable.

E.ramination of the organs. —Heart, spleen, kidney, liver, lung and
suprarenal gland were examined. The portion of the lung examined
showed a condition of pneumonic consolidation going on to grey
liepatization. The arteries show fibrotic thickening with hyaline
degeneration in all the organs, but most marked in the kidney. There is,
moreover, a condition of angio-sclerosis, veins and capillaries as well
showing the chaiioe.

In the liver there is a fibrotic overgrowth around all the vessels in the
portal canal and a fatty infiltration of the liver cells.

The kidneys exhibit well-inaiked interstitial fibrosis with tubular
atrophy; this is especially marked about the region of the looped tubes
of Ilenle, the hyaline fibrotic tissue being in places as abundant as the

LEAD ENCEPHALITIS

127

epithelial parencliynia. The Bowman capsules are markedly thickened,
and the glomerular loop also ap[)ears shrunktui, and marked hyaline
degeneration is apparent. In some of the capsules the vascular loops
appear to have been destroyed and rt^placed by a hyaline purple-
stained mass; in some cases there is still evidence of it having
been a vascular coil, in others this is (|uite lost, ami there is nothing
l(‘tt but the very much thickened hyalim‘ (h*gen(*rated capsule and a
substance like it which hlls the anvi pi(‘viousIy oeciijiied ]ty the glome¬
rular vessels; these are quite numerous. The capsule of the organ is
markedly thickened and fibrous, anil from it tli(‘re extends into the
kidney substance, dense librous bands.

Many of the tubes are denuded of epithelium, in others the epithe¬
lium is degrenerated. Numbers of the tube's contain casts seen in section
and easily recognisi'd bv a diftusi* dull purple stain. The organ is in
a fairlv advanci'd stage of chronic insterstitial fibrosis [ride Fig. S,
Plate I.).

II. —Chemical Examination.

The remainder of the brain (both hemispheresj was dried and inciner¬
ated, and then extracted with liot dilute nitric acid after repeated in¬
cinerations, and finally extracted once with ammonium acetate solution.
The filtrates were cajllected and evaporated to dryness, and taken up in
dilute nitric acid.

No trace of lead present by qualitative or microscopic (Copper Potas¬
sium Nitrite Method*) tests.

Remarks .—Two brains from li'ad workers in the Pottery district were
sent to me some time ago from the Hereford County Asylum. Upon
microscopic examination, one proved to be a typical case of general
paralysis; the other was a case of lead encephalitis with polyneuritis.
Both were considered to be general paralysis, but then we know that
in former times Korsakow’s paralysis was called general paralysis. In
the case of polyneuritic psycliosis in the lead worker, it was extraordi¬
nary how marked was t!ie perinuclear chromotolysis of the giant pyra¬
mids, very much the same as in the case reported, but more widespread
and extensive. The neuroglia cell proliferation was also marked, and
there was a widespread hyaline degeneration of the small vessels (arterio-
capillary fibrosis), but there was no perivascular lymphocyte and plasma

* Evaporate aoluTioii !■> <lrviu‘ss. arid a f(‘\v drop'i dilute acetir acid. Transfer to microscope
slide ; add one drop copper aeetaU' solution, one droji sodium acetate '•olution. and twf) or thr<*e
drops saturated pota<Jsium nitrate solution; stir with a platinum wire: allow to stain! for a
few minutes, and examine under inicroseope. Violet black (mbesof Kj (hi Pb (NOj)(j willap{)car
if lead is present in a fiiiantity exceeding: O’OCtno.S nu/.

128

AKCUIVES

cell infiltration, or any marked atrophy of the superficial layers ol
pyramids, although there was a neuroglia proliferation. In the case of
general paralysis in the lead worker there was marked atrophy of the
ganglion cells, distortion of Meynert’s columns, dissolution, disintegra¬
tion, and decay of ganglion cells, increase of vessels and neuroglia cells
and fibres, and, as Fig. 9, Plate I., shows, marked perivascular cell in¬
filtration.

In Ur. Stewart^s case it is difficult to decide how far the symptoms
observed during life, and the changes in the organs noted post mortem
are due to a single factor—lead, or to the combination of lead, chronic
alcoholism, and renal inadequacy with uraemia. We know, however,
that chronic lead poisoning may be the single factor in the production
of a profound metabolic change and in the establishment of a chronic
progressive sclerotic condition of the vascular system, and that this may
lead to renal sclerosis and an extensive rise of the blood pressure in the
arterial system, which, while being in a measure preservative and com¬
pensatory, nevertheless by the continuous hypertension tends to damage
the whole arterial system, including that of the central nervous system.
The vascular degeneration is due, then, to a chronic toxsemia and
hypertension. It is not necessary to assume that symptoms of ence¬
phalitis in a lead worker means that there is lead deposited in the brain
in small quantities. Uixon Mann has found lead in the brain in chronic
lead poisoning, but in several cases which I have examined, including
the brain of this patient of Dr. Stewart’s, I could not find a trace of lead.

The symptoms, however, can be explained quite well; there is
abundant evidence of chronic irritation, viz., thickened membranes,
angio-sclerotic changes causing vascular stasis with microscopic
haemorrhages and congestion, and proliferated glia cells {vide Pigs. 6, 7,
8, Plate I.). The absence of granular ventricles, of perivascular infiltra¬
tion with lymphocytes and glia cells and the existence of normal pyra¬
midal cells .arranged in columns mark a distinction from progressive
paralytic dementia, with which this condition by a careless observer
might be confused.

The healthy condition of the pyramidal layer of cells (vide Fig. 3,
Plate I.), which is always affected markedly in general paralysis, accords
with the statement by Dr. Stewart, that “ he frequently conversed w ith the
patient during the lucid intervals, and his conversation then was rational
and well sustained.’’ The mental condition was, therefore, mainly due
to toxaemia, and not decay and destruction of the neural structures of
the cortex.

The physiognomical expression of tlie individual, as shown in the
photograph, exhibits a wild appearance,” a mild degree of terror and of

LEAD ENCEPHALITIS

129

paiu; it would accord very well with (lelirium truneiLSy which the notes
indicate rather was his condition on admission. At the same time the
notes distinctly state that he had not been drinking recently. Cases
of pseudo-general paralysis have been described due to lead, and though
more likely to occur in those who are intemperate yet it occurs in those
who are temperate, and theivfore must be due, directly or indii’ectly, to
the lead poisoning. There is usually in such cases a sudden onset with
violent delirium, motor restlessness, epileptiform seizures and hallucina¬
tions generally of a terrifying character, associated wdth loss of memoiy,
mental confusion, and delusions of persecution, of being followed

or of being poisoned. These syinjitoms combined with muscular tremors
and speech affection make up a clinical picture in some respects very like
general paralysis; but the history of lead jioisoning, the sudden onset,
and the hallucinations of sight and hearing together with lucid intervals
are unlike ordinary general paralysis and more like delirium tremens,
Thei’e was apparently some evidence of lead accumulation observed in
this case in the abdominal organs at the post-mortem examination;
sections of the liver, however, were cut and placed in ammonium
sulphide without any definite apparent change. The fact that although
his wife was a widow and had had four healthy children by her first
husband, “and although she was still in the child-bearing age’' had no
children by this man (although he was not impotent), is in support cd
the pernicious influence of the lead on his whole body; tor there is a
(considerable amount of evidence to show that chronic lead poisoning
affects the germ plasm in the male and produces sterility. In the
female, it is well hnown and an accepted fact, that lead poisoning
produces sterility, miscarriages and aliortion; it is even taken by women
in the form of emplastrum plumbi as an abortifacient.

Dr. Oliver, in his interesting article in Clifford Allbutt’s system of
medicine, states that only a few cases have ended fatally, and in these
the post-mortem appearances were those of ordinary general paralysis; on
chemical analysis, however, lead was found in the brain. In this case I
have shown that the microscopic appearances were not like general
paralysis neither were the macroscopic appearances. The brain weight
was that of an average man; there w'as only slight excess of fluid and
therefore there could have been but little wasting, and there were no
granulations in the ventricles. It might be argued, therefore, that this
was not a case of lead encephalitis. Von Jacksh (Die Vergiftungen
NothnageTs system), however, describes the case of a young female
porcelain painter who died with all the signs and symptoms of severe
brain affection, yet no trace of lead could be found in 529 grammes of
brain substance. So that it is difficult to decide whether the case of

I

Dr. Stewart's, above recorded skould be regarded as one of cbronic lead
encephalitis or a chronic encephalitis indirectly due to the effect of lead
l)y the changes this poison has worked in the body in causing an inter¬
stitial nephritis and arterio-sclerosis, which combined with chronic
alcoholism caused a meningo-encephalitis. Von Jacksh points out that
chronic lead poisoning interferes with the oxidation processes and leads
to gout and interstitial nephritis.

DESCRIPTION OF PLATE 1.

Fig. 1.—Three colls from anterior horn of the spinal cord cervical enlargement, show¬
ing one large eell with verj marked chromatolysis, the Nissl grannies ai’e
almost absent; adjacent are two fairly normal smaller spinal motor cells.
Magnificatioji 4-00.

Fig. ‘2.—Giant pyramidal cell from motor area with marked chromatolysis and
eccentric nucleus. Magnification too.

Fig. —Two large pyramidal (association) cells, sliowing normal Nissl granules and
processes. Magnification iloO.

Fig. t.—Giant pyramid from tlie face area of the motor cortex, showing less advanced
change of the cytoplasm ; thei-e is a perinuclear chromatolysis, and the
nucleus is eccentric. Magnification 400.

Fig. o.—Small cells of Vagal nucleus of the medulla, showing various stages and
degrees of perinuclear chromatolysis. Magnification ^0.

Fig. G.—Cortex stained by Cajal silver method, showing a large mesoglia coll sending
processes on to the wall of a small vessel. These neuroglia cells were
extraordinarily numerous throughout the grey matter of the cortex and in
the subjacent white matter. Magnification 4410.

Fig. 7.—Small hyaline degenerated arteriole in the pia-arachnoid of the spinal cord.

This shows the usual appearance met with in the small vessels, and is typical
of arterio-sclerosis (arterio-capillary fibrosis). Magnification 750.

Pig. 8.—Section of the base of a ]iyramid of the renal cortex ; it shows marked
interstitial fibrosis; a number of the tubules are devoid of epithelium and
contain casts—stained deep purple by the hsematoxylin. Magnification 250.

Fig. —Section of cerebral cortex of a worker in lead who died of progressive
paralytic dementia (G.P.I.). The perivascular infiltration wdth lymphocytes
and ])lasma cells is shown. Magnification 200.

Fig. I

Cervical Cord.

Cortex

Cortex.

Nucleus, Magj. 400,

Cortex.

Fig. 9.

Cerebral Vessel. G.P.I.
Mag. 200.

131

A CASli OF EMBOLISM OF THE ANTERIOR DIVISION OF THE
LEFT MIDDLE CEREBRAL ARTERY.

By F. W. MOTT, M.l).. F.R.S., F.H.C.P.

The notes of this case are very deficient ; 1 only once saw the patient
myself. For this reason the brain was not kept for mic roscopic investiga¬
tion, but tliere are some points of interest worthy of record.

Case Book Notes.

A. G., aet. 49. Admitted to Claybiiry Asylum, transferred from
Fisher ton House, 1/11/94.

History previous to adviissio/i. —Married. Occupation, artificial flower
maker. Alcoholic excess.

Medical certificate. —Noisy, raving and violent. Tears at those around
her. Refuses food. Seems to be under the delusion that her daughter is
being murdered. Restless and constantly dressing and undressing
herself.

Condition on admission. — Physicfd: Has marked right facial
paralysis, lips and face drawn over to the left side. Marked motor
aphasia. Articulation very thick and indistinct. Deep reflexes
exaggerated on right side. Inco-ordination of right arm and leg. Heart
hypertrophied. Lungs impaired resonance and coarse rales at the left
apex. Pupils irregular, react to light and accommodation.

Mental .—^Uuiet and obedient, depressed at times, very incoherent,
speech bad, cannot be understood. Melancholic in appearance. Clean
in her habits. Eats and sleeps well.

21/12/94: Mania, with general paralysis. Incoherent, unable to
answer questions.

21/12/96 : Secondary dementia. Excited and noisy at times. Aphasia,
and her memory is impaii*ed, also her articulation, and it is difficult to
understand what she says.

22/5/98: Resfless, noisy, dances wildly about the airing court, and as
her right leg is somewhat spastic her movements are more or less in a
circle, from left to right. At times very spiteful and bad tempered.

20/12/99: Recurrent mania. Memory mucli impaired. No idea of
time or place. Restless, noisv and abusive.

I 2

132

AllCHlVKS

2/12/U2: Getting worse mentally, being more lost, dirty and dennmted.
More feeble and cannot walk well.

30/(1/03; Is in bed in D.I. in a very feeble state, and in the last stage
of general paralysis. Pupils 2 mm., contour regular. K. J.'s exaggerated.
Muscular movements very inco-ordinate. Speech inarticulate. Breathing
broncliial with moist rales over both lungs, most maiked at left apex.
There is much detraction at both apices.

4/7/03 : Died this evening at 6.2S p.m.

In October, 1897, my attention was called to the case, and 1 took tin'
following notes: —

She is suffering from facial paralysis, very marked of the right lowin’
half of the face with tongue deviating to the right; there is some
riglit homiparesis. Knee jerks very exaggerated, patellar and ankle clonus
(»f right leg. Marked wrist t^p and triceps jerk on right side. She
has a fairly good grasp with the right hand, hut she is unable to write or ust a
needle^ which she 3ould do before she had the apoplectic attack. She can pick up
a needle with the right thumb and foretinger and she helps in various ways in
the wards. She carried a cup filled with water to her lips by placing the cup uu
the jDalm of the right hand and then grasping with the thumb and fingers. She
could not take it with safety by the handle.

She can close both eyes, but neither one indeiiendently, although she tried to
do so. She understands ercryihinij that is said to her, and quite understands every¬
thing that is written don'ii. The following questions were asked her in writing or
orally. She iiidicateil by an affirmative or negative sign of the head, as she was
quite unable to express her thoughts in comprehensible spoken language; the
words were usually either misplaced, inappropriate, or incomprehensible owing
to her difficulty of utterance. Sentences in which the words had any logical
sequence were not uttered. She understands what is said to her for she olu^ys
ciunmands.

The following sentences w’ere written down: —

Did you lose consciousness w^hen you were paralyst'd?—To tliis (jiiestion she
made signs and gestures that slie was asle<‘p wlu*n slie lost her speech.

Had she a fit?—Negative sign.

Had you any headache?—Negative sign.

Were you in good health?—Affirmative sign.

Could you walk the next day after you lost your sjieech ?—Affirmative,

Could you use your hand?—l*artial aflirmafiv(‘, pcniiting to her hand as if
weakened.

Your age is 54 ?—Affirmative.

Are you married ?—Affirmative.

Have you a son ?—Affirmative.

Have you a daughter?—Affirmative.

When making these signs slie would fry tn speak, but I could not understand
what she said.

How long have you lost your spti ch. 4 or oyt^ars^—This was written down and
she pointed to 5.

EMBOLISM OF LEFT MIDDLE CEREUKAL ARTERY

166

Pupils equal, I'eact to light ami acconnnociatiou. Some hemiparesis of leg
and arm, but gait is not hemiplegic ; the leg is somewhat spastic. She occasionally
has attacks of excitement which are, I am informed, followed by depression. It
swnied to me that this was partially due to the fact that she could understand,
but could not make others understand her wants; for she indicated to me by signs
and occasionally words that she wished to go away from tliese people.

Diagnosis .—Softening with destruction of Broca's convolution and of the face
and arm centres of the left hemisphere.

Abstract of post-morlem notes: —

Emaciated. Poor physique. Muscles pale and wasted.

Abdomen distended and becoming greenisli-purple in colour.

Nebula on front of right cornea.

Considerable excess of fluid in sub-dural and sub-arachnoid spaces.

The greater part of the central convolutions of the left hemisphere are
markedly wasted and softened. The whole brain was removed and placed
in Muller’s fluid for further examination. Weight 1,210 grammes.

Fourth ventricle only very faintly granular.

Pons, medulla and cerebellum: Weight 175 grammes.

Neck : Small movable tumor of skin in region of thyroid cartilage.

Thorao !.—Right pleura, apical adhesions. Left pleura, generalised
adhesions.

Bronchi: Congested and mdematous. Broncliial glands: Enlarged,
but not caseous.

Right lung: GSO grammes, apex nodular. No caseation or cavitation.
Whole lung mdematous and congested.

Left lung: 590 grammes: old adherent pleuiisy, witli forjnation of
calcareous plate over posterior border; the organ was carnihed.

Heart: Muscle substance soft and flabby.

Valves: Old endocarditis of mitral valve.

Coronary arteries: Orifices atheromatous.

Aorta: Atheromatous especially in descending part.

Ahdonien. —Liver: Fatty, fibroid and covered with lympli.

Kidneys: Fatty, cortex diminished, capsule strips leaving granular
surface.

(huieralised |)erii()niti8 and acute intestinal obstruction from volvulus
of large intestine.

Cause of death : —

1. Acute intestinal obstruction from volvulus with generalised
})eritonitis.

2. Endocarditis, mitral valve.

6. Old embolism of ant(‘rior division of hdl ]iiiddh‘ ccu’ebral. Soften¬
ing of the left bemisphere corresponding to its ar(m of distribution.

ARCHIVES

i;;4

Brain .—(Jii reuioving the membranes the lollowinj^ appt‘arances were
noticed:—As a result of embolism of the left middle cerebral artery
probably only the anterior branch (as judged from the area of softening)
was blocked. The temporal lobe presents no appearance of softening or
atrophy, the lesion being limited below by the sylvian tissure. The
superior frontal and the anterior half of the second frontal present no
atrophic change; it may be remarked that the second frontal is
reduplicated, consisting of two convolutions, which connected at their
anterior end are joined with the first frontal. Tlie posterior half of the
lower division of the second frontal presents an atrophied appearance
with little depressions on its surface indicating thickening of the mem¬
branes. The third frontal, or rather what remains of it, is atrophied
similarly to the second frontal. The part of it corresponding to Broca’s
convolution, namely, the jmrs basilaris, with its connection to the ascend¬
ing frontal has completely disappeared. The atrophy also involves the
pars triangularis and extends to the pars orbitalis; this extension of the
atrophy to the oibital surface becomes apparent on comparison with the
right hemisphere.

Central convolutions: The whole of the lower two-thirds of tlie
ascending frontal and ascending parietal convolutions are involved in
the lesion, the upper part corresponding to the leg area is not involved
owing to its supply by the anterior cerebral; thus the portions of the
central convolutions which are connected in front to the superior frontal
convolution and posteriorly to the superior parietal lobule are unaffected.

The lower third of the inferior parietal lobule, including the
marginal, is atrophied, and on section it is seen that the Island of Reil
is atrophied in its whole extent, as well as the upper portions of the
gyri transversales which connect the temporal and parietal lobes. As the
photograph of the left hemisphere shows, the first temporal convolution,
including its posterior third, is entirely free from atrophy. There is a
little atrophy, as shown by a worm-eaten appearance, in tlTe second and
third temporal convolutions of the left hemisphere, but not like that due
to embolic softening. It is probably the result of secondary atrophy of
functionally correlated structures. Examination of the right hemisphere
shows the following remarkable changes: A secondary symmetrical
atrophy of the second and third frontal convolutions, whereas the superior
frontal shows but little change. The posterior half of the second frontal
and the greater part of the third frontal exhibit a shrivelled and worm-
eaten appearance like that which appears in various regions described on
the left side. There appears also to be a slight secondary atrophy of the
lower two-thirds of the central convolutions, but this is not so apparent.
Elsewhere the right hemisphere presents no structural defects. These

EMBOLISM OF LEFT MIDDLE CEREBRAL ARTERY

i:;5

tluiiiges are in all probability due to atrophy of association fibivs which
connect similar functionally correlated regions of the two hemispheres.

Spinal cord ,—There was well-marked naked-eye degenerative sclerosis
of the direct tract which could be traced down the left side of the spinal
cord as far as the eighth doisaL There was well-marked ditfuso
degenerative sclerosis in the right-crossed pyramidal tract which was
less evident.

Remarks .—It is certain that this patient did speak, altliougli it was
for the most part incomprehensible jargon, still there was not a complete
motor aphasia. When I saw her I came to the conclusion that we should
iind the lesion that was discovered jmst mortem. The secondary atrophy
in the same convolutions of the opposite hemisphere and in associated
structures concerned with the function of speech of the same hemisphere
is of interest. Also the fact that the second and third temporal convolu¬
tions of the left hemisphere should show a more marked secondary
atrophy than is seen in the first temporal, would suggest some functional
association of this portion of the cortex with the region of the brain most
atrophied, viz., the lower two-thirds of the central convolutions.

13G

A BACTERIOLOUICAL INVESTIGATION OF (GENERAL

PARALYSIS*

By J. P. handler, M.A., M.D. (Cantah), D.P.H., Assistant Pathologist to the

London County Asylums.

SUMMARY.

PAGE

IXTRODT CTION . ... ... .. ... . . lo7

Description of Methods Employed .. .. . ... ...

The Examination of Post-Mortem Matehlai.11)8-141

ObserrationvS on the study of Post-Moitem Material ... I ll-Ml!

Examination of Urine and Urethras of Living Peu.sons ... . 142

Examination of Urine of General Paralytics ... ... M2-Mil

Examination of Urethras of General Panilytics ... ... ... M^l

Examination of Urine of cases other than General Paralysis M3

Examination of Urethra.s of cases otlier than General Paralysis M3

Observations on the above Investigations . . Ml

Examination of the Blood and Cekebuospinal Fluid witiiduawn duhing

Life . . . Ml

Analysis of Inve.stigations . Mh

The Presence of Diphtheroid Organisms in Nature.M6-M8

Conclusions on a hove Investigations .. . . ... ... ... J 1-8

The Biicillus Bfinth/fictinH of Ford Robertson ... ... M8-LM

The Preseni k of Bacteria in Films of the Brmn and Meninges 131-l."i:i

The Experimental Production of General Paralysis in Rats . l.S2-l3il

The Value of Antisera Treatment . ... 133-131

Summary .. . 13i

Illustrations.

Acceptel a.s a thesis for the »leprcc of M.D. of CamhrMt^^e University.

BACTERIOLOGICAL INVESTIGATION OF GENERAL PARALYSIS

137

intkodi:(;tion.

The purpose of tliis thesis is to describe the result of a reseurcli in
which I have been engaged for nearly a year in the Pathological
Laboratory of the London County Asylums, and to record the conclu¬
sions at which I have arrived as the result thereof.

The line of study was suggested to me by Dr. F. W. Mott, the
Director of the Laboratory, as one suitable for investigation, and also
because of the theory which has recently been brought forward that
general paralysis of the insane is a bacterial toxaemia dependent upon
the action of a certain group or groups of diphtheroid organisms.

My investigations, which have been mainly directed to the detection
and isolation of diphtheroid organisms from cases of general paralysis,
and as a control, from other forms of insanity, have comprised: —

(1) The examination of the blood, cerebrospinal fluid, respiratory,
alimentary and genito-urinary tracts of the cadaver.

(2) The examination of the urine and uVethras during life.

(3) The examination of the circulating blood, and the cerebrospinal
fluid withdrawn by lumbar puncture, during life.

For the sake of clearness I propose to record tlie result of my
investigations in the order I have mentioned, but first I would briefly
state the main objects I had in view at the commencement and through¬
out the whole of the work. The special organisms which I wislied to
detect and isolate were to be those which could be grouped under the
class of dij^htheria-lik^ hacilli, with the exception of the bacillus of
Hofmann, which has not been suggested as an etiological factor in the
production of general paralysis*

Description of Methods Employed.

The media employed during the course of the res(‘arch wtue;
bouillon, agar-agar, serum agar, blood serum, gelatine, peptone wafer,
potato, and solutions of the sugars in 1% peptone water. In
the earlier part of the investigation byno-haemoglobin agar, made from
Allen and Hanbury's byno-htemoglobin, Avas prepared and used according
to the instructions of Dr. Ford Robertson, who claimed that this medium
caused the metachromatic granules or polar bodies, so frequently seen
in stained films of diphtheria-like organisms, to stand out with special
clearness. In a few instances I was able to confirm this observation,
but I found that the medium in most instances tended to produce atypical
forms, while the cultures quickly died out; latterly, therefore, T decided
to abandon it.

138

AUCHIVES

For staining roaLlions, Loefiler’s metliylenc blue, eiirbolic Uietliylene
blue, Gram's stain and 2Seisser's method for the ditferentiation of polar
bodies were used; the latter stain, however, showed no advantages
over well-prepared specimens stained by either of the methylene blue
})reparation8.

For the separation of diphtheroid bacilli from colonies of other micro¬
organisms which might be present, I used, in nearly every case, Petri
dishes containing a thin layer of solidified blood serum, serum agar or
agar-agar. After preparation, these plates were placed in the incubator
at 37° C. for 24 hours to ensure that they were sterile. They were used as
follows : One or mogre loopfuls of the suspension to be plated were deposited
on the medium in the Petri dish and smeared over the surface by means
of a sterile L-shaped glass rod; a second and third plate were similarly
smeared with the glass rod without further addition of the suspension.
In this way it was possible to obtain a plate which contained a fair
number of colonies, sufficiently discrete to allow of their isolation and
examination. This method is in common use for diluting suspensions
of intestinal bacteria over the surface of plates containing special solid
media such as MacConkey’s bile salt agar, or the Conradi-Drigalski
medium, and possesses the advantage over other methods of plate cul¬
tivation that any colonies which appear are situate on the surface of the
medium and can be dealt with readily.

The Examination of Post-Moetem Mateeial.

The bloi'd, cerebrospinal fluid, respiratory, alimentary and urinary
tracts of 84 cases were examined. Twenty-five of these were general
paralytics and the remaining 59 comprised other forms of insanity.

The method of collecting the material was as follows: —

The heart was raised so as to expose the inferior vena cava; the wall
of this vessel was seared with a cautery; the sharp end of a sterile glass
pipette thrust into the lumen and five to ten cubic centimetres of blood-
were removed from the vein and distributed into two or three tubes of
sferile bouillon which were placed in the 37° C. incubator for further
observation. The cerebrospinal fluid was obtained by thrusting a sterile
glass pipette into the lateral ventricle through the corpus callosum,
while the brain was still m situ. The spot for puncture was exposed by
gently separating the cerebral hemispheres so as to display the corpus
callosum freely, the searing iron being applied to a small part of the
surface previous to the introduction of the pipette. Part of the cerebro¬
spinal fluid was pipetted into a sterile centrifugal tube and the centri¬
fugal ised deposit smeared over the surface of sterile agar or serum agar

liACTKRIOLO(iICAL IXVKSTIGATIOX OF GENERAL PARALYSIS

131J

j)lati*s, while a seeojid sample was placed in a sterile culture tube without
the addition of any culture media.

The material from the lungs was obtained by inserting a stout
looped platinum wire down one of the smaller bronchi. A tube of
bouillon and a series of slanted blood serum and agar tubes were inocu¬
lated. Scrapings from the mucous membrane of tlie stomach and
intestine wore tieated in a similar manner. The serous surface was
seared with the cautery and the incisions into these organs were made
with sterile instruments. The urine was collected from the bladder by
means of a sterile pipette, which was thrust through the wall of the
organ after the surface had been tlioroughly seared; the centrifugalised
deposit of about 10 c.c. was at once plated, while, as a control, about
1 to 2 c.c. of the urine were pipetted into a broth tube. All the cultures
obtained were placed at once in the 37^ C. incubator and examined at th(‘
end of 12 to 24 hours for the presence of diphtheroid bacilli. In success¬
ful cases these were isolated and sown in pure culture over the surface
of blood serum tubes and their morphological characters and cultural
reactions on other media recorded.

The 25 cases of general paralysis so examined yielded diphtheroid
organisms in three, or 12?o*

In Case I. a diphtheroid organism was obtained in pure culture from
the blood, and from the respiratory tract in association with other
organisms. A film preparation from the cerebn)spinal fluid, after
incubation, showed the presence of a bacillus similar to that obtained
from the respiratory tract in very scant numbers among a host of other
organisms; attempts to isolate it were not successful. The organism
obtained from the blood was very typical and differed in many respects
from that isolated from the respiratory tract, which appeared to belong
to a different species. The principal characters of the former, after
cultivation on blood serum for 24 hours were as follows:—A non-motile,
non-sporing, Gram-positive organism. Stained with Lceffler’s methylene
blue, the bacilli were of medium length, very slender and straight or
slightly curved.

At this stage of growth they pre.sented the chaiacters of taper¬
ing bacilli, each of which appeared to possess a definite unstained
transverse septum, causing the organism to look like two bacilli of
triangular shape with their bases in apposition. The ends of the
bacilli tapered to an exti’cmely fine point, and, in many instances,
stained very faintly (the so-called sheath form). Metachromatic
granules were present in abundance. The characteristic grouping of
the diphtheria bacilli was well seen in stained preparations (Fig. I.).

After two to three months’ incubatimi at 20 ^ C. tlm bacilli had lost

140

ARCHIVES

some of tlieir original characters, there being a tendency on the
part of some to stain very faintly, while some slender thread forms were
also found. The number of bacilli with metacliromatic granules was
far less than in the original cultuie and tho Neisser reaction w^as very
faintly marked.

Cultivation ~Ovi agar and blood serum plates the colonies appeared as
small circular dots at the end of 48 to 72 hours, rather opaque, w hite
in colour, the centre somewhat raised and denser than the periphery,
of wrhich the margin was quite regular (I'ig. XIV.). In size they varied
from 2 to 4 mm. in diameter.

In bouillon the grow th was attended by an initial turbidity, followed
by the deposition of a finely granular deposit on the sides of the test
tube.

On potato the growth was invisible to the naked eye.

In litmus milk media the growth was not attended by any apparent
change.

A well-marked acid reaction occurred in glucose peptone water, but
the organism had no ell'ect on lactose.

No liquefaction of gelatine occurred after six weeks’ incubation at

200 c.

The inoculation of bacillary emulsion into a guinea-pig produced no
result.

From the same case the respiratory system, including both the trachea
and bronchus, yielded a diphtheroid organism, which differed in several
characteristics from that isolated from the blood in pure culture. In
stained preparations the bacilli were almost completely of the segmented
variety and somewhat longer and thicker. Here and there in the
methylene blue preparation a few^ granules could be seen, but they were
not displayed by the Neisser stain; the ends of some of these bacilli
w ere decidedly pear-shaped or bulbous.

The growth on all solid media was far more luxuriant and moist than
in the case of the true diphtheria bacillus, and the individual colonies
were of larger size.

In bouillon the growth w'as attended by a decided turbidity without
any deposit on the sides of the tube.

A visible dirty grey coloration attended the growth on potat-o.

The growth in milk gave rise to slight acidity but no coagulation.

There was no liquefaction of gelatine.

Qrowdh in glucose peptone water gave mai ked acid reaction; t he
lactose peptone water remained unchanged.

The organism was non-motile, non-sporing and Gram-positive. It
was also non-pathogenic to guinea-pigs.

BACTElllOLOCaCAL lAVESTIGATlUN UE UEXEKAL rAtt.AJLYSIS

141

lu Case II. a diphtheroid organism was isolated from the respiratory
tract of a general paralytic which iigi'ced morphoh^ically and culturally
with that obtained from the respiratory tract of Case 1.

In Case III. an organism of the diphtheroid species was isolated
from the base of one of several circular erosions of the stomach of a
general paralytic.

The grow’th on all solid media was very luxuriant and moist with laigr*
individual colonies.

On potato the growth was dirty grey in colour, moist and luxuriant.

The reaction in glucose peptone water was acid but in lactose peptone
water no visible change occurred.

in bouillon there was a general turbidity, and after two days a
somewhat stringy deposit had settled at the bottom of the test tube.

The growth in milk showed no visible alteration and there was no
liquefaction of gelatine.

Stained specimens of a 24 hours’ grow’th on blood serum showed the
pi*(»sence of bacilli of medium length but stouter than the true diphtheria
bacillus. Polar .bodies were present in almost every bacillus, but they
were only very faintly stained by the Jseisser method. The organism
was lion-motile, non-sporing and Gram-positive (Fig. VII.).

Fifty-nine cases of insanity other than general paralysis were
examined jjod mortem in a similar manner.

Diphtheroid organisms were isolated in four cases or G'G%. In three
of the cases they were isolated from the respiratory tract and in the
fourth case from a scraping of the urethral mucous membrane. The
type obtained from this region was similar to that obtained from the
u retinas of cases examined during life and to w^hich I shall shortly refer.

Of the three cases obtained from the respiratory tract, one agreed in
all characteristics with those obtained from the respiratory system of
general paralytics. The other two were similar to the diphtheria
bacillus in staining reactions and cultural characters, but were of an
extremely short variety. They w^ere not patliogenic to guinea-pigs.

Observations on tue Study of Post-Mortem Material.

The study of iwd~moriem material for the presence of diphtheroid
organisms presents many difficulties. Firstly, the blood and cerebro¬
spinal fluid become invaded with organisms of all varieties immediately
or shoitly after deatli, and even with the aid of a cold chamber for the
reception of bodies previous to autojisy it was rarely that I found these
tw^o fluids sterile, although I exercised every precaution to prevent
external contamination. Secondly, the respiratory and alimentary
systems contained such a wealth of organisms that the isolation of the

142

Alien IVES

diphtheroid species involved a considerable amount of labour, and it is
possible that in some cases they may have been outgi*own or overlooked
amongst the other forms which were present. Therefore I do not con¬
sider that observations attended Avith these difficulties should be looked
on as of accurate statistical value; at the same time, however, my own
observations do not lead me to think that diphtheroid bacilli are present
in the cadaver with a sufficient degree of frequency to justify any claim
to their importance.

Examination oe the Uhine and Uhethras of Living Persons.

My attention was next directed to the examination of the genito¬
urinary tract of living individuals by reason of the statement of Dr. Ford
Robertson that diphtheroid bacilli could be found in the urine of cases
of general paralysis and locomotor ataxia with very considerable fre¬
quency. The method which I used for the examination was as follows: —

The urine Avas collected into sterile vessels after careful cleansing of
the meatus urivarius and wdthdraAval by means of a sterile catheter.
Part of the ceiitrifugalised deposit of about 10 cc. of urine was at once
plated, Avhile a second portion was placed into a tube of sterile bouillon.

Cultures from the urethra were obtained by inserting a small
platinum loop as far as possible into the urethra after careful cleansing
of the meatus. The loop Avas rotated several times in the canal and then
smeared OA^er the surface of tAvo or more tubes of slanted blood serum
and agar-agar. All the cultures so made Avere examined after 12 to 24
hours’ incubation at 37^ C.

Examination of the Urine of General Paralytics.

Twenty-six cases of general paralysis yielded a diphtheroid bacillus
in two cases, or 7*6%.

The two examples of diphtheroids obtained possessed identically
similar characters. They Avere non-motile, non-sporing. Gram-positive
organisms. On blood serum at the end of 24 hours the bacilli were of
siiort to medium length, straight or slightly curved and grouped in
small clusters. The granular type of bacillus was by far the most
constant, but segmented forms were occasionally present. After 24 hours’
growth on blood serum, pear-shaped and bulbous forms were frequently
to be seen (Fig. V.).

On agar plates the colonies were sIoav to make their appearance and
then became visible as small, extremely delicate, pearly white, circular
colonies with even margins, someAvffiat similar to the growth of a strepto¬
coccus, with some tendency to adhere to the surface of the medium
(Fig. X\.). The increase in size of the colonies was slow, but after five

BACTKRTOL()(iICAL IWESTTGATIOX OF GENERAL TAEALYSIS

14a

or six days they became more spread out with margins slightly irregular
and the centre raised and umbiiicated.

In bouillon the growth was accompanied by a very tine granular
precipitate, the supernatant fluid remaining clear.

Milk remained unchanged.

There was slight acid reaction in glucose peptone water, but none in
lactose.

The growth on potato was invisible.

There was no liquefaction of gelatine and the growth on this medium
was extremely scant.

Inoculation of guinea-pigs produced no effect.

Examination of the Uretiihas of General Paralytics.

Thirty-one cases of general paralysis yielded diplitheroid organisms
in 5 or 16%.

The first diplitlieioid isolated was identical with tliose obtained from
the urine.

The rest differed in only one particular, viz., that the colonies on agar
plates were visible to tlie naked eye at an earlier date, and at the end of
76 hours showed a small but definite central umbilication, the growth
from this to the periphery being flat and the margins slightly irregular.
The colonies were somewhat flaky and did not tend to adhere closely to
the surface of the medium (Fig. XVI.).

In bouillon the growth was attended by the formation of a very
delicate scum or pellicle, a similar appearance being noted over the
water of condensation at the bottom of the slanted agar tube. Micro¬
scopically there was no difference between this variety and that obtained
from the urine.

Examination of the Urine of Cases of Insanity other than

Gener.\l Paralysis.

The urine of 28 cases of insanity other than general paralysis yielded
a diphtheroid bacillus in one case, or 8*5%. It agreed in morphology
and culture with those isolated from the urine of general paralytics.

Examination of the Urethras of Cases of Insanity other than

General Paralysis.

From 44 cases of insanity other than general paralysis diphtheroid
bacilli were isolated in 6» or 13*6%. All the types were similar to those
already described (Figs. VI. and XVII.).

144

ARCHIVES

OliSEllYATlO.NS ON THE AliOVE Iv\ AMI NATIONS.

The examination of the genito-urinary tract of cases of general
paralysis and other forms of insanity has revealed the presence of
diphtheroid organisms which have dilYered in certain characteristics from
those met with in other parts of the human body as ascertained from
post-mortem investigation. Although not absolutely identical with the
bacillus xerosis, they are, in my opinion, very closely allied to members
of that group.

It is rather difficult to decide with certainty as to what part of the
genito-urinary systeui attords a nidus for these organisms. In my
opinion the examination of the urine, whether withdrawn by catheter or
after it has been voided in the usual wav, will fail to decide whether
tlie organisms have come from the urethra or from the bladder, as by
either method contamination with urethral organisms appears to be un¬
avoidable. I am inclined to think that they exist mainly in the urethra,
as I have not been able to obtain a growth of diphtheroid organisms
from the urine which has been withdrawn at autopsy by puncture of
the fundus of the bladder.

I^XAMINATION • OF THE CIRCULATING BlOOD AND CERElillOSriN AL ElI ID
WITHDRAWN BY LuMBAR PuNCTURE.

Tccliniy^ue .—Blood in amounts varjdng from 5 to 20 cc. was removc<l
from the basilic vein into a sterilised syringe containing a small amount
of potassium citrate solution. The greater part of the blood was at once
s(piirte<l into a tlask containing about 100 cc. of sterile bouillon. As a
control 0*5 to 2 cc. of the remaining blood w^as placed in a culture tul>e
containing 10 oc. of broth.. In addition the surface of a slanted agar
and blood serum tube was also smeared over wTth drops of blood. In
several cases anserobic methods of cultivation w’ere used in addition to the
ordinary procedure. The cultures were in the majority of cases transferred
at once to the 37^ C. incubator, but in a few instances they were placed for
12 to 24 hours in the ice chamber prior to incubation, as Dr. Ford Robert¬
son has suggested, in order to diminish the possibility of phagocytic or
lysogenic action of the blood, which, he asserts, destroys the diphtheroid
organisms before they have an opportunity of multiplying in the culture
medium. Previous to the withdrawal of the blood the skin of the arm was
carefully cleansed to avoid as far as possible contamination from this
source.

I have examined the blood of 27 cases of general paralysis on 45
different occasions during life, some cas(‘s liaving been utilised more than
once. In no single instance liave I been successful in obtaining a

UACTKKlOLOCaCAJ. IXVKSTKJATiON OK OKMvHAL i’AUALVSIS

14o

culture oi u diplitheroiJ bacillus. The majority ot the cases selected
were advanced cases of general paralysis, nearly all of wliom have since
died, and tlie clinical diagnosis has been verified at autopsy. In five of
the cases the blood was obtained during the progress of, or shortly after,
the terinination of epileptiform seizures.

In 12 of the cases special efforts were made to obtain a culture of a
diphtheroid bticillus from tlie bouillon flask inoculated with the bbxMl
ot a general paralytic. After incubation at 37^ C. for two to three days
20 to 30 c.c. were pipetted into two or more sterile centrifugal tubes, and
the deposit thus obtained was smeared over tlie surface of sterile agar
plates, or, as an alternative, was distributed into tubes of liquefied agar,
and plates poured in the usual way. This method was adopted because
by its use Dr. llobertson, of the Moniingside Asylum, claims to have
isolated a diplitheroid organism of the xerosis type from the circulating
bloofl of several cases of general paralysis. My attempts to obtain a
growth of a diphtheroid organism by this technique were unsuccessful.
Xor have 1 ever seen, in stained films of the circulating blood or in
films prepared from the centrifugalised deposit of a bouillon flask after
incubation, any organisms which I could accept as resembling diph¬
theroid bacilli.

The presenco oi other organisms in the circulating blood of general
paralytics: —

In seven iustaiices during my examination ot the circulating blood
I have obtained growths occuning in the broth flasks and tubes which
I have been unable to account for on the theory of external contamina¬
tion, although this is extremely liable to occur from the skin and from
the atmosphere (vide Fig. XYIII.).

In four instances the organism was a staphylc<K*cus albiis; in one
ihe colon bacillus; in one a small diplo-bacillus with occasional long
forms resembling the bacillus of Friedlander; in one case a small
delicate streptococcus, which was later obtained in pure culture from
the heart blood at autopsy (Figs. XI. and XII.). Those were all obtained
from rapidly progressing cases of general paralysis and were probably
factors in the production of the fatal termination.

Examination of the cerebrospinal fluid withdrawn by lumbar punc¬
ture during life: —

The cerebrospinal fluid of nine cases of general paralysis and one of
tabes dorsalis was examined. In the last seven cases the centrifugalised
deposit of 10 c.c. was plated directly in a manner similar to that used
in the examination of the blood, and the rest of the fluid was placed in
broth tubes and on the surface of slant agar tubes. I did not succeed

K

14U

AlM'tllVKS

in ohiiiinin^ a of a ilijilillioroid organism from tin's neither

did I s(*e any diphtheroid bacilli in srain(‘<l films of the d(‘j>osi(.

Analysis of tiif Uksi lt of niw : An()\K Invkstioatiox.

7'he (.tffmIfuUion of jKfsf-tnorttin ;///////•/<//. -Twen(y-hvt‘ cases of
ji^eiKoal ]»aralysis yiehh'd diphlheroi<ls in or r-i",,. Fifty-nine

(*ases of insanity other than »:('mMal paralysis yitdded diphtheroids in
four, or h ti'/o.

K.ramindiioti of ilo (j( nito-urnKny tvifvf. Fifty-s(‘ven cast's of general
])aralysis yit'ldt'd di])htheroids in seven, or Sevt'iOy-two (*ast's

of iiisaniiv othei* than ^^i*m*ra! ])aral\sis yit'hit'd diphtheroids in st'ven,
or

The total numher of cast's examined vas 21*), 82 of which were cases
of p^t'neial ])aralysis and 1*J1 wt'ie of other forms t)f insanity.

The percentage incidence of diplnheroid organisms in general
paralysis was 12’2, while in other foiins of insanity it was 8*4.

I liave not included in these figures the cases in which the blootl
ami cerebrospinal fluid were examined during life, the results of which,
as far as diphtheroid organisms are conct'rned, were entirely negative.

The Preskxck of Diphthekoid Okoanisms in Nature.

Kvidence of the ubiqiiitoiis nature of the diplitheroid group of
organisms has rapidly accumulated since the discovery of the Klebs-
Loeffler bacillus. Organisms resembling the true diphtheria bacillus
have been found in almost every part of the luiman body and also in
domestic animals and birds, some virulent and others non-virulent to
laboratory animals and to man. Graham Smith gives a very complete
hibliogra])hy wlierein they are staled to have been found in the normal
(*ye, the mouth, nose, ear, the lesions of vaccinia and variola, the lesions
of leprosy, eczema and other skin lesions, the female genital organs, tin'
male urethra, the urine, the pus of a livt'r abscess, the valvular lesions
of ulcerative endocarditis, milk, the lungs of rats, the eyes of normal
guiiK'a pigs and dogs, the mouths of diseased and normal birds, etc.

Hudson and Paiiton in an investigation of 105 cases of acute (*on-
junctivitis, found diphtheroid bacilli in no less than 60.

Stanziale obtained a diphtheria-like bacillus in 12 out of 27 cases
from the normal uretlnal mucous membrane. He (|Uotes the work of
Pfeiffer, who in 15 examinations of normal urethras found diphtheria-
like bacilli in 11.

Stuart McDonald found diphtheria-like bacilli in tin' oerebrospina!
iluid of cei’i'brospinal nn'iiingitis on thr(*(* occasions, during a seri('s of

BACTERIOLCKilCAL I \ YESTlli AT[()N OF GEA ERAL FAllALYSIS

147

ov(‘r 40 autopsies; iu two instances in assoeiatioii with tlie inenin^ococcus
and once in pure culture.

Morrell and Wolf record a case of ineningilis, from the cerebro¬
spinal tluid of wliich, both by lumbar puncture during life and also after
death, a diphtheroid organism was isolated.

At a meeting of the Medico-Psychological Association in May, 1907,
the frequency of diphtheroid organisms in cases unassociated witli
insanity was commented upon by Dr. Eyre, of Guy's Hospital, and
Dr. Dean, of the Lister Institute. Dr. Eyre stated that during tlie
routine examination of from 500 to GOO specimens he had found
diphtlieroid organisms in the cerebrospinal fluid withdrawn during life,
and from tlie plural exudate of a case of tuberculosis meningitis; also
twice in cultivations of blood from cases of suspected infectiv(‘
endocarditis, once in a case of tuberculosis cystitis, and once from material
(d>(ained from a case of disease of the antrum. He also stated that those
who had any experience in the examination of material obtained from
general hospitals were aware that diphtheroid organisms were of
extremely frequent occurrence.

Dr. Dean also commented upon the extraordinarily wide distribution
of diphtheroid bacilli in nature; that they were frequently met with in
disease, iu accidental association with the organism responsible for that
ilisease; also that they could be found in many normal conditions, e.g.,
in the male and female smegma and other sebaceous secretions, in urine,
and very commonly in milk, which might possibly account for their
presence in the stomach of eases of general paralysis. He also stateil that
Dr. Arkwright, working at the Lister Institute, had found diphtheroid
organisms in two out of seven cases of suspected cerebrovspinal meningitis
in which he examined the brain and meninges post mortem. Purtlier,
out of 24 cases in which he had examined cerebrospinal fluid he found
diphtheroid organisms on two occasions. These were sometimes asso¬
ciated with other organisms such as the meningococcus.

In view of these facts he thought that great caution should be
observed in accepting any diphtheroid organism as having a causal
relation to general paralysis, unless it possessed well-marked ctiaractcris-
tics, including pathogenic action on experimental animals.

The incidence of diphtheroid organisms in cases of general paralysis
and other forms of insanity has formed the subject of an investigation
by Eyre and Flashnian, who found diphtheroid organisms present in
10 0% of general paralytics, as compared with 17*0% of other forms of
Insanity. Their conclusions were based on the examination of the
throats of a large number of cases suffering from all forms of insanity
and also of material obtained at post-mortem examinations. They state<l

K *2

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that ill their hands diphtlu'ioids could not be iscdated from eas(‘s of
general paralysis any more readily than from other torms of insanity.

Dr. George Robertson, oi the ilorningside Asylum, claims to
have isolated a dijjhtheroid bacillus from tlie circulating blood or cerebro¬
spinal fluid of seven out of 14 cases of general paralysis; in three of
these the organism is stated to have been seen in stained preparations of
the fresh blood. He states that his organism is not identical with Rerd
Robert son’s linrilltts whicli he has never isolated. He lias

also found the same bacillus in other forms of insanity in aciiti' cases.

Conclusions.

The conclusions at which 1 have arrived as th(‘ r(‘sult of my own
investigations, together with those obtained by other (dismvers, aie:---

(1) That diphtheroid oiganisms, sonn* pathogimic and others non-
virulent to man and animals, are extremely common organisms in
nature.

(2) That they can be found with considerable fie(|uency and i*epre-
senting several different sjiecies in all parts of the human bculy, but
especially on serous and mucous surfaces.

(d) That the genito-urinary tract affords a very frequent nidus for
some varieties.

(4) That diphtheroid organisms may be found either in pure culture
or associated with other micro-organisms in diseases which have bcvui
proved beyond doubt to be due to another specific factor.

(5) That my own observations lead me to believe that diphtheroid
brganisms cannot be isolated from cases of general paralysis with any
greater ease or frequency than from cases unassociated with that disease.

(6) That during tlie progress of general paralysis the impairment of
tissue resistance facilitates the occasional entry of micro-organisms into
the blood stream.

(7) That the organisms which gain ejitry are not confined to any
particular species, but may include st'veral varieties among which,
according to the obseivations of others, the diphtheroid class must be
included.

The Bacillus Paralyticans of Ford Roukrtsox.

In a series of articles which have ajipeared from time to time during
the last few years I)rs. Ford Robei tson and McRae have claimed that an
organism of the diphtheroid species is the specific (diological factor in
general paralysis and tabes. The contention of these observers seems
to be that, although such agents as syjihilis, alcohol and excess of nitro¬
genous diet, individually or collectively, may serve as predisposing

IJACTKIHUUH.ICAL IXVESTiliATIO.N UF GENERAL PARALYSIS

149

tactois by undermining the tissue resistance, yet without the Bacillus
j/aralyticans there can be no general paralysis or tabes.

The grounds on which they have based their contention appear to

be:

(1) The discovery of diphtheroid organisms with great frequency in
the alimentary, respiratory, and genito-urinary system of all cases of
advancing general paralysis.

(2) The experimental production of general paralysis in rats.

(3) T)ie success which they claim to have attended the treatment of
certain cases of general paralysis and tabes dorsalis by vaccines and
antisera prepared from their organisms.

I will therefore draw attention to some of the statements they have
made in support of their claims, and will attempt to criticise such of them
that appear to require further substantiation.

Firstly, with respect to the frequency of diphtheroid organisms in
cases of general paralysis, Ford Robertson and McRae state: “The
evidence that a diphtheroid bacillus—either an attenuated form of the
Klebs-Loffler bacillus or more probably an altogether distinct micro-
organh'sin—is the specific etiological factor in general paralysis and tabes
dorsalis is briefly as follows: A bacillus of tliis nature is, according to
the results of our investigations, present in large numbers, either in the
alimentaiy or respiratory tract, or in both, and in the genito-urinary tract,
in all cases of advancing general paralysis. This bacillus has a thread
form, which has been found invading the walls of the respiratory or
alimentary tract in five cases of general paralysis. It can be shown that
this bacillus invades tJie pulmonary tissues in cases of general paralysis,
and it is commonly the only micro-organism present in large numbers
in the catarrhal pneumonic foci that occur in most of such cases dying
in congestive attacks. A growth of a diphtheroid bacillus has now been
obtained in cultures made from the brain jwst mortem in ten cUvses <jf
geneial paralj^sis out of 24 in which cultures were made from this organ.
Diphtheroid bacilli exhibiting metacliromatic granules in Neisser pre¬
parations have been detected in the fresli blood in one case and in sections
of the brain in two cases. It has been ascertained by experimental
methods that these diphtheroid bacilli in contact with the living blood
are rapidly taken up by the polymorpho-nuclear leucocytes, and that
tliey may be completely digested in the course of two or three hours.
Dodies exactly corresponding in appearance to these dissolving bacilli
can be detected in the blood and the cerebrospinal fluid of the living
general paralytic, es|)ecialiy during a congestive attack. Whilst the
fact that most of the bacilli present are in process of disintegration
satisfactorily explains the long succession of negative results of

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eudeuvours to obtain cultures from the blood and cerebrospinal fluid,
we have, by the use of special metliods, succeeded in obtaining pure
growths of a diphtheroid bacillus from the fresh blood in four cases of
general paralysis, and from the cerebrospinal ftuid withdrawn by lumbar
puncture in two cases. In sections of the brain prepared by special
metiiods disintegrating diphtheroid bacilli can be recognised in the walls
of the vessels and in the pia-arachnoid in many cases of general paralysis.
The centrifuge deposit from the urine of the general paralytic, especially
during a congestive seizure, commonly contains abundant diphtheroid
bacilli that have been more or less attected by lysogenic action. ' In
seven consecutive cases of general paralysis, combined with tabes, we
have found the centrifuge deposit from the urine to contain, not only
these altered diphtheroid bacilli, but also living ones, showing distinct
metachromatic granules. In such cases a culture of the bacillus can
be obtained from the ifrine.’^

Further obseivations have led them to suppose that there are at least
two types of diphtheroid bacilli capable of producing general paralysis
and tal)es dorsalis. These they have named Bacillus 2 jara'hjticafis Ion (fits
and Bacillus i^aralyticans brevis respectively, the latter bearing a close
resfeniblance to the bacillus xerosis and being found most frequently in
the urine. Furthermore they have suggested that the frequency with
wliich diphtheroid organisms can be found in cases free from mental
disorder has no particular bearing upon the point at issue; but, if their
organism is to be classified as specific, it must be shown to possess special
distinctive characters. These the Bacillus paralyticans has not yet been
shown to ])ossess so tar as morphology and cultural characters are con¬
cerned, and until its specific pathogenic property has been conclusively
dejuonstjated, I maintain that the presence of organisms of a similar
species in cases une.lVected with general paralysis cannot be considered
to be of secondary imj)ortance.

■JMio great difficulty which these observers have ex])erienced in cul¬
tivating th(‘ diphtheroid organisms from the circulating blood and
cerebrospinal fluid is worthy of consideration. This apparently cannot
be due to paucity of numbers, for bacilli possessing metachromatic
granules are stated to have been seen in stained films made from a drop
of the circulating biood. They must therefore be present on occasions
in the bh)od stream in enormous numbers to allow’ of their identification
in a blood film and should certainly be capable of cultivation if two or
three cubic centimetres be jdaced into a suitable culture medium and
incubated at body temperature.

The r(*ason assigned by Ford T{obe]ts{)n for this failure is that (he
bacilli an' rendcued inert, parlly by the pliagocytic properties of the

BACTEUIOLOUICAL iXVKSTKiATlOX Ol- (iKMOUAL TAUALYSIS

151

lt*iioocytA‘s, and partly by the lysogenic! aethni of the blood .serum, and
other fluids. As evidenee of this he states that in stained films of the
blood, cerebrospinal fluid and urine, and in sections of the brain,
bodies corresponding to dissolving diphtheroid bacilli are almost con¬
stantly present. 1 have examined a considerable number of stained
films of the blood, cerebrospinal fluid, and sections of the brain, and
have never been able to detect diphtheroid bacilli. With regard to the
debris seen in films of the cerebrospinal fluid and in sections of the brain
1 think it would be very difficult to form any precise opinion as to its
nature, and moie difficult still to recognise disintegrating bacilli.

This lysogenic action of the serum has been disputed by Dr. Bulloch,
Bacteriologist to the London HosjDital, who states: “ If diphtheroid
bacilli exist in the blood or cerebrospinal fluid of general paralysis they
should be capable of cultivation at once without waiting for the cessation
of any supposed bactericidal action, for no lysogenic action of the serum
for bacilli of this group has been proved to exist.’'

My own experiments performed in vitro do not support the observa¬
tions of Ford Hobeitson. I have subjected two strains of diphtheroid
bacilli obtained from cases of general paralysis to prolonged contact
with the serum of patients suffering from that disease. Emulsions from
a 24 hours’ agar culture of the organisms have been mixed with fresli
s(vrum from a general paralytic in known proportions, and placed in
sealed tubes in the 37° 0. incubator for 24 hours. Control experiments
with normal serum were made. The contents of the tubes were then
blown out into melted agar and plates poured in the usual way. The
results obtained, as estimated by the number of colonies growing up on
the plate cultures, showed practically no difference in inhibitory powc^r
between the two types of serum employed. Further, stained films made
fiom the diphtheroid bacilli which liad been exposed to the action of
undiluted serum of general paralytics for 24 hours at 37° C. showed
little if anv alteration in the sluipe and staining reactions of the bacilli.
(Compare Figs. I., TI., TIL, IV.)

Tilt: PuKSENCK oE Bactkiua IX Films of the Brain ano Me.mnoes.

Dr. Ford Itobertson statics that he lias found diphtheroid bacilli with
imuachromatic granule's prc'sent in sections of the brain of general
])aralytics on two occasions. I have been unable to confirm these obser¬
vations. On the other hand I have found bacteria of various kinds present
in the stained films of the brain and meninges, and I show three photo¬
micrographs to illusi rate this])oint. Fig. VIII. shows micro-organisms in
a smear prejiaratiou of the coitex of a female general paralytic. I’his

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patient died from the exhaustion of very severe and numerous epilepti¬
form seizures. The autopsy wus performed one hour after death. The
blood and cerebrospinal fluid both contained several varieties of micro¬
organisms on cultivation, but diphtheroid bacilli were not found. Fig. IX.
shows micro-organisms in a smear preparation from the cortex of a male
general paralytic made 22 hours after death, the body in the meantime
having rested in the cold chamber. Fig. X. shows a strepto-bacillus in
anotJier field of the same preparation. I produce it to emphasise how
deceptive microscopic evidence might be. This strepto-bacillus possesses
several very well defined and deeply stained granules. Had this organism
been broken up into two or three portions during tlie preparation of the
film the separate parts would have borne a remarkable resemblance to
diphtheroid bacilli with metachromatic granules. Tliese three photo¬
micrographs, especially the first, serve to substantiate what I have pre¬
viously said concerning the almost invariable presence of micro¬
organisms in the blood and cerebrospinal fluid obtained jwst mortem^
and offers presumptive evidence of microbial invasion of the tissues in
the terminal stages of the disease.

The Experimental Production oe General Paralysis in Pats.

Through tlie kindness of Hr. Leathern, Bacteriologist of Charing
Cross Hospital, I have been able to observe the result of some feeding
and inoculation experiments on white rats. Tliese were carried out in
the laboratory of Charing Cross Hospital by Dr. Leathern, who on tlie
death of the animals forwarded them to me for examination.

The organisms used in the experiments were obtained— ((i) from the
blood pod tnortern; (b) from the genito-urinary systmn of cases of general
paralysis. Seven rats have been examined which have died after the
course of feeding and nine which were subjected to inoculation. The
latter were inoculated twice in the early part of August, 1907, with
0’25 c.c. emulsion of a 24 hours’ agar culture. All died between the
dates of Tth November and 2nd December, 1907, having survived about
three to four months from the date of the first inoculation. In the feeding
experiments eacli of the animals received tuice weekly 0*5 c.c. of an
emulsion of tlie diphtheroid organisms mixed with its food. The
dui'ation of life from the commencement of feeding was three to four
montlis. Control animals remained healthy. The fact that practically
all the animals subjected to the experiments died, while the controls
remained healthy, suggests that the former succumbed to the toxic
action of the organisms. This, however, is no proof of the specificity of
these organisms in general paralysis; and sections of the brain showed
no changes suggestive of (hat disease. Cultures were taken from the

HACTERIOUX.U'AL IN VKsTKi ATION OE (iKNKRAE P AttAEVSIS

1 53

tissues of the aniiuals after death, but diphtheroid bacilli were not
demonstrable.

The X'alue of Axtiseka Treatment.

Dr. Ford Itobertson has claimed for antisera prepared from his two
types of diphtheroid bacilli valuable curative and diagnostic properties.
Of the use of this material I have no personal experience.

It is to be remembered that beneficial results of a more or less
transitory nature have from time to time been advocated from the
employment of other remedies such as anti-diphtheric serum, defibrinated
blood withdrawn from a case of general paralysis and inoculated into
another; fibro-lysin in a case of locomotor ataxia, etc. Moreover,
remissions in the course of this disease may be of such duration as to
simulate recovery and give rise to false impressions as to the value
of any particular line of treatment which is being adopted. I hold it,
therefore, to be wise to await a more extended use of this serum before
it is universally accepted as a specific for general paralysis. With
regard to the diagnostic value, the author states that whether the serum
be given by the mouth or hypodermically, the rise of temperature which
follows it is characteristic and, in his opinion, diagnostic. Now it is
well recognised that general paralytics are frenuently the subjects of
irregular pyrexia produced by the varied coni]dications to which they
are liable. It would have been advisable, therefore, to have clearly
stated that every precaution had been taken to ensure that the patient
had been entirely free from any pyrexia for some days previous to the
inoculation. In regard to the control cases it is stated that: “ In none
of these did any specific reaction occur after mouth administration, and
any rise of temperature subse([uent to injection could readily be explained
by other factors.’* Explanation as to what these factors were is certainly
desirable if the importance of the reaction is t(» be fully appreciated.

In conclusion I would like to draw aliimtion to a recent publication
of Dr. A. Marie. This writer states tliat as the lesult of a visit to the
Morningside Laboratory in 1904 he was stimulated to follow up the
researches of Ford Eobertson. Dacteriological examination was first
made of the urine and different tissues, notably the nervous system,
cerebrospinal fluid and blood, but he was unable to find the Tidril/us
pnrahjticanii. Cultures of the ctMobrospinal fluid gave no result. In
the blood he only found strepto-bacilli and staphylococci. Intra-peritonea 1
injections of the Bacillus paralyticans (sent to him) into white rats were
unproductive. Experiments with regard to opsonisation and sero-
agglutination in his hands ])roduced anomalous results. In con.se(|uence
he believes that the Bacillus parafj/fleans is not the spc'cific factor in

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154

general paralysis, but only an epij)lnuu)nienon and an element in the
production of secondary infections.

Summary.

With the opinion of Marie I am in entire agreement. That general
paralytics are liable to secondary infections and complications is not
disputed; moreover, it is possible that diphtheroid bacilli may pbiv
some part in these secondary infections and tliat the use of an anti¬
serum prepared from such bacilli may be attended with transitory bene-
ticial effects.

The assumption, however, that a particular group or groups of
diphtheigid organisms act as the specific factor in the production of
general paralysis is unwarranted and has not yet been substantiated by
any published research.

In conclusion, I desiie to thank Dr. F. W. Mott for the interest he
has taken in the work and for his manv suggest iems. I am also indebted
to Dr. (j. F. Barham and Dr. W. S. Iluglies, who kindly obtained for im‘
a large amount of material in the wards.

REFKRHNCKS.

(1) Eyiu’. and Kl. ashman. Ih-H. MrfL Jininnil. Octolua* and ArrJnns •>/

Ntnu'ohKfijy vol. iii., H>07.

(*J) Fkrkiek and (Bui.locii). “The Liiinlcian Lccliii'cs.” lOoO.

(•^) (jiiAUAM Smith. Jitvnnt! nf Ififijienr, July,

(!•) Hudson and I’anton. Limrri^ July 0, 1007.

(5) Makie, a. Societc dc Biologic*, Seance de '17 Juilh‘t, 1007 .

(h) Mark, Hamilton. /icr/r/»- Xw-rohKjif miA psj/rji{ah'i/, ISOveiuher, I00!s.

(7) McDonald, Sti akt. Hrrirv) XviimltHfif aiul /'.s/yr/t/fz/r;/, Se|)teinlK‘r. 10o7.

(S) Mokkei.i, and \V()LK. Jnnnuil Anirrii'im Mctfirtil l)ec(*inl)er 20, lOUd.

(0) Ncttall and (Iraham Smith. Thr narh rinfiHji/ of I)l 1!mi^.

(lOj lloitEKTsoN, (ji. M. iSrii. MrA. JotirneJ, Se|)t(*inlM‘i* 2S, JlM>7.

(11) Rohektson. W. Ford. Hcru tr Xi iinthuiij n hA rff. Aprd, .Max, J lily, 10o:>;

May, 1007); Fehriiary. Marcli, .V|)ril, lOoH; June, Sepleuiher, 1007.

Brit. Mrd. JoifrntA, July 20, 1001.

„ ,, Octolu*!* 26. lOOl.

,, ,. (Ictoher 21, lOod.

JonnuA if Mrntnl Scii’ficCy July, 1!>07.

(12) Stan/.iale. C>')ilriflhlnlt fUr iycA’/rr/M/f*////, August, looo.

ADDFNDU.M.

Sinci' till* above arlicli* was written, Dr. Hamilton Marr lias n^corded
the results of a bacteriological examination of tin.* cendirospinal fluid of
od cases of gmieral paralysis. In no single instance did he succet‘d in
cultivating a bacillus or any othciorganism from the fluid.

PLATE I

Fig. I.

Diphtheroid organism isointed in pure
culture from the blood of a general
paralytic {post-niorUm), Blood serum,
24 hours’ growth. Mag. 1,500.

Fig. II.

Same organism as Fig. I. after several
sub-cultures on Agar. Mag. 1,500.

V

Fig. III.

Diphtheroid organism (Fig. II.') after
24 hours’ exposure to the undiluted
serum of a general paralytic. Mag. 1,500.

Fig. IV.

Diphtlieroid organism (Fig. III.) after
re-cultivation for 24 hours on blood
serum. Mag. 1,500.

X/

f-

" 1

' ' y

Fio, V.

A diphtheroid organism isolated from
the urine of a male general paralytic
during life. Blood serum, 24 hours’
growth. Mag. 1,600,

Fig. VI.

A diphtheroid organism isolated from
the urethra of a case of senile mania
during life. Blood serum, 24 hours’
growth. Mag. 1,500.

fnce p. 154.

PLATK II.

Fig. VII.

A diphtheroid organism isolated from
the stomach of a general paralytic post¬
mortem, Blood serum, 24 hours’ growth.
Mag. 1,000.

Fig. VIII.

A smear preparation from the cortex
of a female general paralytic (one hour
after death), Mag. 1,000.

Fig. IX.

A smear preparation from the cortex
of a general paralytic (22 hours after
death). Mag. 1,000.

Fig. XL

Growth in bouillon from the circu¬
lating blood of a general paralytic.

This organism was also obtained in
pure culture post-mortem from the blood
of same case. Mag. 1,000.

Fig. X.

A smear preparation from the cortex
of a general paralytic. Same case as
Fig. IX. Mag. 1,000.

Fig. XII.

The same organism as shown in
Fig. XI. Film made from the water of
condensation of an Agar tube after trans¬
plantation from broth. Mag. 1,000.

^ac€ p. 154.

PLATE 111.

Fig. XIII.

Colony of a Kleb's-Liiffler bacillus on
Agar plate (76 hours).

Co^^par»^ margin with that of the
\ colonies shown in following four figures.
Mag. 5.

Fig. XV.

Colonies of a diphtheroid organism on
Agar plate, 76 hours, from the urine of a

f sneral paralytic (same organism as
ig. V.). Mag. 5.

Fig. XIV.

Colony of a diphtheroid organism
(same as Fig. I.) on Agar plate, 76 hours.
Mag. 5.

Fig. XVI.

Colonies of a diphtheroid organism on
Agar plate, 76 hours, from the urethra
of a general paralytic. Mag. 6.

Fig. XVII.

Colonies of a diphtheroid organism on
Agar plate, 76 hours, from the urethra
of a case of simple mania. Mag. 5.

Face p.

PLATE IV.

Fig. XVIII.

Photographs of Agar plat3s exposed for 15 to 20 minutes to the air of the general paralytic
ward during the taking of blood cultures. Four-ninths original size.

(To illustrate one of the liabilities to external contamination during this procedure.)

Face p. 154 .

155

llJiMOUKHAGE lATO THE SmiAllENAL ( APSl LI-:.
By J. P. CANDLEK, M.A., M.l). {Vastwi.), D.P.H.

Tile object of the following paper is to record two cases of liitMUorrhage
into file siiprarejial capsule which were recentlj' found on the post-modern
table of the London County Asylum at CTaybury within three months of
each other. The second of these cases is of esjiecial interest in that the
patient showed symptoms pointing to some obscure abdominal trouble
shortly before death: —

Cask I.— Bk. xii., Fol. 7. W. J. L., a widower, was a<lniilted to the Asylmii on
the 24lh of November, 1900, and died Mareh Gth, 1908.

He is descnbed on admission as l>ein.i' a poorly nourislied, miserable old man <d
72, suffering from senile dementia, and in poor lieulth and condition.

His physical state on admission is describ(*d as folh>w's : “Tongue furred,
edentulous. Reduplicated first sound at apex of heart. Complete arcus senilis.
(Edema of feet.”

He gradually became more feeble, and on the oth of March, 1908, he had a
syncopal attack.

He was put to bed and examined. His pulsi* rate was 02 per minute, and very
feelde. There was evidence of commencing lung cimsnlidation. The patient never
rallied, and died on the following day.

The jmst-mortem examination revealed the presmice of generalised arterio-sclerosis,
granular kidneys, and cardiac enlargement. Iliere were several old cerebral soften¬
ings situate in the basal ganglia, and also scattertKl over the cenbral cortex. '1 he
lungs weIV congested and oedeinatous, and in placi-s were consolidated.

The left supraivnal capsule wuis disintegrated. The right was enlargerl to the.
dimensions of a walnut, and on section was found to be tilled with recent blood
clot. {Vide Fig. I., Plate I.).

A microscopic examiniition was made of the various tissues to confirm
the post-modern findings. The mednllary portion of the suprarenal
capsule had been entirely replaced and destroyed by a recent luemorrbagie
extravasation.

This, so far as could he seen, was confined to that region and had not
invaded the cortical portion of the cajisiile. The cells, however, in this
region had nearly all undergone a necrotic change.

A microscopic examination of the kidneys showed a very marked
degree of interstitial fibrosis.

(A\si: TT.7*1., F(tl. 140. I. B. IT.. m;ilc. iigcd 71, was admillcd l<» the
Asylum on December 21th, 1900. and died DceemlKT 19lh, 1907. This patient

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alsu wa; llu? subjc*ct of senik* doiiu-iitia. His physical condition was oxtrenioly
feeble. The bjllowiiig details of his last few weeks of life are of inlerost : —

Oil November :20th, 1007, he was seized wdth a snb-aciite attack of diarrhoea, from
which he recovertnl.

On I)eceinl>er Idth he fell as he was being assisted in from the airing court;
an attendant jiartly broke his fall, but he sustained an abrasion over his right eye.

On December 17th the patient had a kind of syncopal attack. Dulse rate 1(K),
ainl of fair tension.

On December 18th he had a temperature of lO'iO'^ and f^igus of broncho¬
pneumonia. He was apparently suffering from severe abdominal pain, for lie
groaned repeatedly and drew up his knees. 'Hie abdomen was distemled and
resonant on percussion, but there was dulness in the tlanks. 'llie bowels w^ere C('n-
fined. Patient <lied on Deceml)er 19th.

At the st-mortem examination there w’cn* found general arttu-io-seku-osis ami
some cardiac enlargement, with incii‘ase in density of the renal tissue. There was
a patch of old yell<;w s<dtening in the right (x;n*ebral hemisphere. There was marked
purulent bronchitis and hypostatic pneumonia.

Both suprarenal capsules w\*re found to Ik* very much enlarged, and on s<^ction
were hlle«l with clot of the colour and cniisisteiicy of rec(*ntly shed blood {rii/r
Fig. IT, IMate L). The right caj)sule was laig<‘r than tin* left, iKungd cm. in length,
d cm. in width, and 2 cm. in breadth. There was no extravasathui of blood into
the periadrenal tissue, or into the peritoneum.

Microscopic exjunination showed that in the case of both ca])sules the hajinorrhage
was mainly situate iii, and ha<l completely dc*stTV)yed the imslullary j)ortion. dlie
cortical j)ai't showed a largo numlK?r of very distende<l capillaries and some
extravasation of bl<x>d. nie colls in this regi<ui had undergone a considerable degrei-
of necridic change.

The kidneys show'od a marked dt‘gix‘e of interstitial fibrosis.

Tlie discovery of tliese two cases induced me to examiue the jfosf-
morlcni legistei’s in ordm* to ascertain the frequency of visible luemorrhagc
into the suprarenal eapsule in the insane, as shown by the records of
tills iiistitutioii, and to note in how many eases symptoms had been present
wliieli pointed to the existence of any abdominal trouble prior to death.
1 liave therefore inserted in tabular form a list of all cases of suprarenal
luemorrhage out of a tfital number of 1,926 jwst-morton investigations
held oil all forms of insanity.

From a perusal of the literature it would aj)pear that haunorrha^e into
the suprar(Mial eapsule may occur as the ri'siilt of ((f) active or (h) passive*
cong:t‘stiou. The former variety appiuirs to be more prevalent in
young' chihli'en and in the still-born, nc<'uiringf in about 4o per cent, of
necropsies, according to.Arnaud. T)r. Still, howc'vor, only found four
cases of suprarenal Ineinonliage in muMopsies on children under

12 yea I S of agfo.

Accoiding' to Dr. Spenu'er, injury at hirih may lx* i(‘sponsible for a
larL»*e nunilx*!’ of cas(*s in the lU'wly-born. Tn youngs childien the disease

I the post-mortem table at the Lonaoi
fcive. Total number, 1,9*26 (males, 937;

Other patholoncal conditions present
in toe body, dtc.

the Vascular de^ifeneration; coronary
I arteries calcareous; cortical
softenings; renal fibrosis; cardiac
hypertrophy.

dney Aneurism of aorta; vascular de-
iarv generation; adherent pericar-
livei’i diuin ; bronchitis and emphysema.

hitis General paralysis of the insane;
men- scars of old syphilis; papilloma of
the bladder with cystitis; a patch
of dense ])early fibrosis in the
aorta; kidneys congested.

ionia| Pulmonary tuberculosis; scattered
iraly- areas of early atheroma and
I ])early wliit^ fibrosis in the aorta ;
I kidneys a|)parently (|uite healthy,
but some slight increase in density.

into!

cap-:

Purulent bronchitis; hypostatic
pneumonia; c^-rebi-al sottening:
general arterioscleiosis; granular
kidneys.

lonia General arteriosclerosis; granular
re. I kidneys; multiple cerebral soft¬
enings.

; hy-i ? Myxoedena ; a moderate amount of
stion; scattered fibrosis generally discri-
I: the buted through the aorta; kidney s
I congested.

lurall

^cute

A moderate degree of atheroma.
Granular kidneys, some cardiac
hypertrophy.

icho-j Nil notewoithy .
and'
effu-
side.l
ofi

onia.. Moderate degre^e of atheroma.
Granular kidneys.

rs before death hieinaturin commenced and
cry collapFcd state.

pinal trouble were noteti on the day before

I

elsewhere.)

nd rapid, but no murmurs.

It. ; females, 0*4 per cent.).

Il.KMOKlin AGK INTO Si rUAllliNAL

157

may supervene during the course of many acute infectious, especially
diphtheria, or may occur quite suddenly in a previously liealthy child,
accompanied by purpuric eruption, fever, and sometimes convulsions,
suggesting the onset of some intense infection. That this acute condition
is due to some toxic origin is rather favoured by the results obtained
by the experimental injection of various micro-organisms into animals,
e.jr., diphtheria bacilli (Iloux and Yersjin), bacillus pyocyaneus (Langlois
and Charrin), Friedliinder’s bacillus (Roger), whereby congestion of tln‘
gland with engorgement and effusion have resulted.

That a similar condition may occur in adults is shown by a case,
reported by Rr. Andrewes, of a medical man, aged 5d, who was suddenly
seized with profuse haemorrhagic purpura and died in a few hours. A
1)1 ood examination showed the presence of meningococci. Pod mortem
both suprarenals were in an intensely haemorrhagic condition, whilst, in
addition, there were cutaneous and subarachnoid haemorrhages.

The characteristic features of these haemorrhages into the suprarenal
capsule are stated by Rr, H. R. Rolleston to be the sudden onset with
lever, j)ain in the hypochondriuni radiating into the loins, convulsions,
vomiting, diarrluea, and later tympanites, colla 2 )se, and death within
48 hours.

In adults, hvemorrhage into the suprarenal capsule is much less
frequent. According to Leconte it occurs once in every hundred cases,
but Arnaud thinks that this rather under-estimates the frequency.

Out of a total number of 1,926 post inortems at Claybury, visible
haemorrhage was found in 10 cases (six males and four females), giving
a frequency of 0’5 per cent. {Vide Table.)

Generalised atheroma is a fertile cause of haemorrhage; consei[uenMy,
age and senility are predisposing factors. As will be seen from the tabh^
only three cases of suprarenal haemorrhage occurred under the age of
40, and two of these were cases of general paralysis of the insane. In
the remaining cases a greater or less degree of vascular degeneration was
present.

The proportion of cases is stated to be greater in the male sex (the
appended table shows a percentage of O’6 per cent, in males as against
0*4 per cent, in females). This may be explained by the greater liability
of the male sex to degenerative changes in the vessels. Predisposing
factors will be found in all the causes which promote venous engorgement
in the general or abdominal circulation, such as cardiac and respiratory
embarrassment, pulmonary tuberculosis, especially noted by Arnaud,
cerebral aflfections accompanied by prolonged coma, etc.

The co-existence of renal lesions, especially of interstitial nephritis,
with haemorrhage into the suprarenal capsule has been noted by Letulle

uiid Pilliet. A rofereiR ‘0 to the table of eases in this paper will show the
marked association of suprarenal htemorrhage with arterial degeneration
and granular and fihrotic kidneys. Phlebitis of the capsular veins and
thrombosis of tlie renal veins have also been noted as being associatetl
with this lesion (Arnaiid, Parrot, Droubaix).

Sympiom(doli)(jy. 'ihe symjitoms are vague and indefinite. Arnaud
has classified them as follows: —

(1) (’ases exhibiting signs of peritonitis or of intra-abdominal
Inemorrhage ca])ab]e of being diagnosed and treated during life.

The author mentions two eases which were signalised by painful
crises, returning at intervals, situated in the epigastrium or in tlie region
of the kidney. The crise.s were accompanied by vomiting. Mattei has
reported the case of a man, aged 60, with an ulcer of the leg, w^ho shortly
after admission was seized with very acute pain in the lower part of the
abdomen and died in 24 hours. No otlier lesion was found post mortem
(*xeept haemorrhage into the suprarenal capsule.

Of the series of ten cases recorded in the accompanying table, one
ease only presented symptoms of abdominal pain, with a somewhat dis-
t(*nded abdomen resonant on percussion, and dulness in the flanks. The
symj)toms are unfortunately very obscure and liable to Tbe confused with
other forms of acute abdominal trouble, especially, perhaps, wdth
luemorrhage pancreatitis. This case, however, shows the importance of
nmiembering the possibility of suprarenal haemorrhage wdien the precise
nature and situation of some acute abdominal trouble cannot be located.

(2) Haemorrhage giving rise to symptoms of suprarenal insufficiency,
such as anaemia, muscular w’eakness, prostration, loss of weight, and
diarrh(ea (witliout bronzing of the skin), and the author thinks that it
wmuld be well to place by the side of the classic malady of Addison a
clinical chapter on “ Suprarenal Syndromata not Addisonian.”

To diagnose a case of liaemorrhage by these symptoms alone would, I
think, be an impossibility. Many cases of insanity exhibit the symptoms
of anaemia, muscular weakness, prostration, and loss of weight. With
regard to diarrlupa it is interesting to note that one of tbe cases recorded
had an attack of sub-acute diarrheea one month before death, but to
assign this solely to suprarenal insufficiency w’ould be unjustifiable,
especially in an asylum wdiere cases of simple diarrlwa and institutional
dysentery frequently occur.

Reference to a paper by T)r. F. W. Mott and Professor Halliburton on
The Suprarenal Glands in Nervous Diseases ’’ show s that suprarenal
insufficiency is common in the insane. In T1 cases of insanity in wdiich
tlie supraix'ne^ glands w’eix> examined clunnically and physiologically,
46*4 per cen‘. gave no reaction or only a faint coloration with Vulpian's

II KMOURHACiK INTO SVPRARRXAL

159

f(‘n ie clilorlde test for adrenalin, and U per cent, oecasioned a fait ot
hlood pressure when injected into rabbits. It is of interest that one ot
lh(‘ r*ases <d lirpmorrhage recorded in the Table (viii., fol. 109) was among
the series of suprarenal glands tested in this way, and both (‘hemicallv
end physiologically showed a deficiency of adrenalin.

(0) Hoeinorrhage accompanied by predominant nervous sym])toms.
These are cases of the utmost importance.

They are characterised by a rapid and unexpected fatal termination
pi (‘ceded or ac companied by grave nervous phenomena, such as convul¬
sions, delirium, or coma without paralysis. For examjile, as Arnaud
slates: ‘‘ A person in full liealth or during the course of some illness of
miiior importance is suddenly struck down with syncope or coma, with
oi' without convulsions, and succumbs after some hours or days without
a?)ything being found to explain the cause of death, the only lesion jfoat
mottem being luemorrhage into the suprarenal capsules. He reports such
a case in a man, aged dG, who was brought into hospital in an un¬
conscious condition, deatli occuiTing in 48 hours without any evidence
b(‘ing forthcoming as to the nature of his malady. Hsemorrhage into the
sujirarenal capsules was the only lesion discovered mortem.

It is of interest to notice that three of the cases which I have recorded
had a severe syncopal attack 24 to 48 hours before death, though it must
be acknowledged that this might have been due to other causes.

Such cases, Arnaud says, are not uncommon. He has met witli 15
similar instances in his observations upon 79 cases of haemorrhage into
tlu'se organs.

The sudden and rapid death is attributed to the damage done to the
adjacent abdominal sympathetic plexus by the luemorriiage into and
distention of the suprarenal capsule.

Vigoroux and Collett have recorded a case of bilateral haemorrhage
into the suprarenal capsule in a general paralytic, aged 50; the symp¬
toms noticed being those of profound coma followed by death. This case
is, so far as they are aware, the first case recorded in a general paralytic.
Out ot the ten cases recorded in these statistics, two occurred in cases of
general paralysis. Haemorrhages occurring in the course of diseases of
the nervous system have also been recorded in chronic meningitis with
cerebral congestion, epilepsy, senile dementia, cerebrospinal meningitis,
and hemiplegia from cerebral haemorrhage.

(4) Cases which give rise to no appreciable symptom, and are not
capable of being attributed to a capsular lesion.

The condition of the suprarenals is only found at necropsy, associated
with some other pathological condition which of itself has been sufficient
to cause death. Several of the cases which I liave recorded must be
included in this group.

AlU’lllVKS

l(i(^

Lastly, there is a ^roup ot cases in whicli death lias occurred and
nothing else lias been found pod mortem beyond liannorrhage into the
suprarenal capsule. Dr. Langdon Drown, in an analysis of 4,110 necrop¬
sies at St. Dartliolomew’s Hospital, n‘ports three such cas<‘s. This
suggests that death and even sudden death may occur from such a
haemorrhage alone, without giving rise to any symptoms. Such a case is
recorded by Dr. Hoodhart in a man sutfering from emphysema, who died
suddenly and without apparent reason, hiemorrhage into the suprarenal
cajisule b(*ing the only lesion found.

CoxcLrsioN.

The importance ot luemorrhage into the suprai-enal capsule li(‘s in
the fact that such a lesion may occur, giving rise to obscure abdominal
or nervous manifestations difficult of diagnosis, and may even be a cause
of death without any appreciable symjitoms whatsoever.

I wish therefore to emphasise the necessity of remembering that such
a condition can occur, and further to urge the imiKudance of carefully
examining the suprarenals in all cases where death has occurred without
any lesion being found in other parts of the body of sufficient gravity to
account for death.

REFERENCES.

(1) AxniiEWEs. “ Patli. Ti’jins,” 190(}, ]). 117-2.

(2) AiiNACn. Arcliiv. "eii. dc* Mrd., Pai'i-s,” P.iOo, t. iv., ]i. 5.

(i») Brown, W. E.wodon. St. B»rtlu)l(>nu‘\v’s Itosp. Reports, vol. xlii., ]). 10.

(4) Droueaix. Quot(‘d by Arnaiid.

(o) Goodhart. “New Sydenliain Society’s Atlas of Path./* London. 1870.
Fa.^c. ii., f. 7>0.

(()) Lanolois and Charrin. “ Soc. do Bioloi^ie.” July, 180:1, and Dec.. iSOd.

(7) LANliMEAD. Laurel, 1004, vol. i., ]). 140t).

(8) Leconte. “ These de Paris,” 1807, ]). 78.

(0) Letulle and Piluet. “ Bulletin Soe. Anat.,” 1889.

(10) Mattki. Lo Sperimentale.” Florence, 188:1, p. :i8(i.

(11) Mott and Hallibi kton. Arehive.s of Neurology,” vol. iii., )). 12:1.

(12) Parrot. Archiv. gt^n. de Med., Paris,” 1872, t. 99, ]>. 2o7.

(13) Roger. “ Soc. do Biologie,” 1894, and “ Presso Med,” 1801.

(14) RoiiLEsT(^N, H. I). Moutrrdl Mrd. Jouriidl^ 1007. Nxxvi., ]). 1171.

(17>) Roux and Yersin. ‘'Anii.de ITnstitur Pastenr.” ISSO.

(10) Si’ENCFR. “Trans. Obstetrical Society.” 18:»1, vol. xwiii.

(17) Stii.e. “ Patli. Trains*’ 1^08. p. -J.Ml.

PLATK I.

Fig. I

Haimorrliage into right suprarenal capsule. (Case I.)

Farr p. 160.

Fig. if.

Hnemorrhage into both suprarenal capsules. (Case II.)

161

THE PHYLOGENESIS OF THE PALJilO-COETEX AND ARCHI-
CORTEX COMPARED WITH THE EVOLUTION OF THE VISUAL

NEO-CORTEX.

By C. U. ARIENS KAPPEKS,

Amaienhim.

Wliile studying the phylogenesis of the rhinencephalon and its con¬
nections I was struck by the great resemblance which its cortical layers
show compared with different stages in the progressive development of
the visual cortex as described by Dr. Mott, and I thought a short com¬
munication thereon might contribute to our knowledge of the principles
underlying the development of the central nervous system.

Before trying to make out these structural analogies I will describe
the progressive evolution of each form of cortex separately, and will first
explain w’hat is meant by the expression i)(d(]eo-cort€x.

As is known Elliot Smith has distinguished two territories
in the pallium of mammalia, the archi-jJtiUium and the neo-pallium^ of
which the first is older, being already present in reptiles, where a neo-
pal liuiu at his time had not yet been demonstrated. The charac¬
teristic feature of the archi-pallium is, that its cortex, the archi-cortex,
receives tertiaiy olfactory fibres, which bring olfactory impressions to it
from the secondary olfactory centres, the neo-cortex receiving tertiary
impressions of non-olfactory character, acoustic and visual impressions,
and impressions of general and special body sensibility. The different
sorts of pallium, however, are not yet exhausted by these two types, as
ill the lower vertebrates, in cyclostomes and selachians, the mantle only
consists of nervous substance, which does not receive tertiary but only
secondary olfactory fibres, and the same is the case with the greater
part of the dorsal nervous wall, which covers the lateral ventricle in
amphibia.

This nervous substance, in order to distinguish it from the sub-
ventricular grey substance, should be called palceo-pallium,^

* This palsBo-pallium is also present in Ganoids and Teleosts, but poorly developed and is
bent outward (latero-ventrally) instead of inward (medio-dorsally). The primary, medial
epistriatum of these fishes replaces a great deal its functions. For further details see the paper
published by Mr. Theunissen and myself on the Phylogenesis of the Rhinencephalon.

L

AKCHIVES

m

It is the oldest nervous mantle occurring in vertebrates, and in
higher vertebrates is pushed ventrally by the great development of the
archi-pallium and especially of the neo-pallium.

Just as in the pallium there can be distinguished three territories
according to the connections which they exhibit, so the cortical structures
occurring in them should be distinguished, according to the same principle,
into a palceo-coHejc, archi-cortex and neo-cortex, of which the first forms
what is often called the cortex olfactoria, cortex lobi olfactorii, cortex lobi
piriformis, etc., which names are better replaced by the expression
palceo-cortexy which indicates its phylogenetic position.*

The place which this latter cortex occupies in lower vertebrates is,
perhaps, strange to our general conception of cortex as it first appears
in its most distinct form in the subventricular wall of the brain and not
in the palaeo-pallium, where the palaeo-cortical arrangement, thougli
present, is not nearly as typical as in the ventral grey substance.t

Fig. 1 shows the structure and position of the typical palaeo-cortex
of a Selachian, scyllium canicula (in many sharks—galeus canis, centro-
phorus, spinax—it is present in exactly the same form). It is evident
that it consists of two layers (I do not speak of the molecular layer in
this short note): a very large and distinct layer of granular cells (Fig. 2)
and underneath this [i.e., nearer the ventricle) a layer which contains
amongst others larger cells, which sometimes are pyramidal in form, in
other parts exhibit very different outlines (Fig. !3): polymorphous cells.
In and above the granular layer secondary olfactory fibres end and
underneath it, mostly from the infragranular cells, tertiary tracts
originate (part of the tr. olfacto-habenularis and of the tr. olfacto-
hypothalamicus rectus et cruciatus).

As is known in amphibia the ganglion cells remain for the greater
part in the stage of the Mantelschicht ’’ of His ; they do not or hardly
ever emigrate from the ventricular ependyma, near which they keep
crowded together. Distinct cortical layers are not formed in the pnlseo-
pallium of these animals. So the next type of a well-differentiated
palaeo-cortex is found in the reptiles (Fig. 4), where it lies in the ventral
and lateral wall. Tlie dorsal and medio-dorsal part of the pallium
contain the archi-cortex, the structure of which will be described here¬
after. What has to be noticed here is that a continuation of the lateral
cortex extends a certain distance over the pars ammonica of the archi-

♦ The expression mostly used until now : cortex olfactoria, is not right because the archi-
cortex is also a cortex olfactoria.

t In Teleopts and Ganoids a real cortical structure does not occur, because the whole
tendency of these brains, where a massive (primary) epistriatum replaces the greatly reduced
palaNi-palliuiii, is to contain the greatest quantity of grey substance with as little superficies as
jMjssible, and so all cells are more crowded together.

PUYLOGKNKSIS OF PAL.150-C0RTEX AND AKCUI-COETEX

1G:J

cortex, which may bo called sujjerposUio lateralis^ and that fibre tracts
from the lateral cortex go into the archi-cortex: filn*8e olfacto-hippocam-
pales extemae, which are partly associative fibres.

A closer study of the lateral cortex shows that it contains many more
pyramidal cells tlian the palseo-cortex of the selachians, and that these
pyramidal cells (Pig. 5) are found chiefly in the dorsal and the caudal
part of it, whereas cells of a granular, stellate and fusiform character,
closely crowded together, are found in its frontal and basal part (Fig. G),
although some of them are also present in the other parts. This
arrangement can be easily understood if we know that the secondary
olfactory fibres finish mostly in the frontal and basal part of this cortex,
whereas the greater tertiary olfactory tracts take their origin in more
dorsal and caudal parts, in the latter of which caudal descending con¬
nections (with the hypothalamus and ganglia habenulae) also originate.

An important thing to mention here is that the upper part of the
lateral cortex layer has certainly already a neo-cortical character, as is
proved by the fact that a certain amount of fibres, originating in a neo-
thalamic nucleus of the fillet (nucl. rotundus: chiefly n. med. thalami of
mammals) end in it. As the nucl. med. thal. (and also the nucl. rotund.)
receive trigeminal fillet-fibres, it results tliat tlie first neocortical tactile
region is one of oral sensibility (just as the first neostriatum). The associ¬
ative part of the dorso-lateral fibres are consequently partly trigeminal-
hippocampal fibres (besides olfacto, hippoc. fibr.). This fii*st neocortical
I'egion is directly continuous with the palaeo-cortex itself.

The most characteristic feature of the palaeo-cortex itself is that
the granule-like cells are less in number and chiefly restricted to the
fronto-basal part, whereas the pyramidal cells, greatly augmented, are
chiefly found in more dorsal and caudal parts, although they are found
also under the granular layer in the fronto-basal part. So the cells of
different type are not as much arranged under each other as next to each
other, side by side.

To comprehend the palseo-cortex of mammnlia, Professor Livini and
I studied marsupials, of which it is necessary to say a few words about
the neo-cortex.

The latter is formed between the archi-cortex and the palaeo-cortex,
originating from the palseo-cortex, with which it is still entirely con¬
tinuous in the reptiles. By its enormous development the archi-pallium,
with the archi-cortex, is pushed medialwards, and is rolled together.
(Compare also Elliot Smith and Gius. Levi.) The palseo-cortex is pushed
ventralwards, and occupies a great deal of the base of the brain and a
small part of its lateral aspect; so its place can be hardly still called
palaeo-pallium, as it is located for the most part under the striatum, but

L 2

164

AKCHIVES

its cortex is liomologous with the palseo-cortex of the reptiles; iu contra¬
distinction to the reptiles the paheo-cortex in nuimnialia is sharply dis¬
tinguished from the neocortex by a deep tissure: the fissura rhinalis
lateralis.

So, the archi-cortex and palaeo-cortex are greatly removed from each
other by the extensive growth of the neo-cortex and the only place where
they are not separated from each other by neo-cortex in the mammalian
brain is the occipital pole of the brain, where the superj^ositio lateralis* is
very striking (Fig. 7) and where the fibrse olfacto-hippocampales externm
—in the reptiles distributed over the whole extent of the lateral wall—
for the greater part are packed together in some thick bundles, which
now form the tr. spheno-ammonicus of Cajal.

It is evident from this that the occipital part represents a region,
found in the dorsal and caudal part of the palseo-cortex of reptiles, which
is confirmed by its structural features, as its cells, arranged in four to six
rows (of which the upper and lower one contain the most of them), are
nearly all pyramidal cells, or at least such of which the type shows that
they are cells with long axis cylinders.

The granular layer—as in the reptiles—is chiefly confined to the
fronto-basal region of the palsBO-cortex (Fig. 8), where it is very pro¬
nounced as well in the form of its cells as in their close arrangementt
(Fig. 9). Under it there is a distinct layer of very large pyramidal
cells (Fig. 10). In this region a great deal of secondary olfactory fibres
end (granular cells) and in the deeper layer tertiary olfactory fibres to
the archi-cortex begin (pyramidal cells).

If we compare the different forms of palseo-cortex, from the selachians
to the mammalia, we see that its progressive evolution goes together with
an increase in number of the pyramidal, larger cell-type. In the selachians
the few larger cells are chiefly located under the very extensive granular
layer, as is found still in the baso-frontal part of the palseo-cortex of
reptiles and mammalia, but in the greater part of the mammalian palaeo-
cortex and in the reptilian the greatly augumented pyramidal cells
are also present next to the granular layer, more side by side.

For the study of the phylogenetic development of the archi-pallium
and archi-cortex we have to begin with the amphibia, where such a cortex
first occurs.

• The superpositio lateralis is also visible between the rest of the Amraonforraation and
the subiculum, reap, the eyrus fomicatns, but less typical. According to my opinion the fibr.
olf.-hipp. ext. contain different fibres, which bring impressions from different regions to the
archi-cortex of which in reptiles the palaeo-cortical connection (packed together in mammals in
the tr. spheno. amm.) prevails. In mammals also fibres from the gyrus fomicatus occur in this
ystcm.

11 cannot understand how Cnjnl can deny the presence of granular cells in the
palap.o-cortex of mammalia. As my drawing shows (here are many of them, as also has been
St ated by Calleja (l.c. p. 33).

t’llYLOiiKNKSIS OF PAL-KO-CORTFX AXJ) AIICIIT-CORTEX 1G5

Tbe prvmordium liippocampiy as one niiglit call the poorly differen¬
tiated archi-cortex of these animals, is, however, too primitive in its
structure for a distinction in layers to be possible.

Granular cells, or rather cells of little differentiated character, form
the greater part of it, and are mixed with some multipolar cells, which
probably send out the little fornix and a part of the commissura pallii of
these animals.* In reptiles, however, a very distinct division in layers is
visible (Fig. 4).

The granules packed together in a dense row of very small cells
(Fig. 11) occupy the whole mesial wall of the pallium and a small part
of the dorsal. The rest of the dorsal wall contains much larger cells of
a pronounced pyramidal type (Fig. 12), which are not at all crowded
together but rather at some distance from each other.

The first layer (A) is the fascia dentata (c.f. Brill, Gius. Levi) and the
latter (B) the ammon-formation, the cells of which have long axis
cylinders that can be traced in the fornix, in the tr. cortico-habenularis
and in the commissurse pallii anterior and posterior (which form the
psalterium of these animals).

In consequence of the fact that the tertiary olfactory fibres reach the
archi-cortex for a great part (directly or indirectly) through the molecu¬
lar layer, the fascia dentata has a somewhat more superficial position
than the ammon-formation, and, though in some reptiles these layers are
continuous over the whole extent of the dorsal surface, in most ophidia
and sauria they are separated more or less, and the ammon-formation
extends a short distance under the fascia dentata {superpositio medialis)
as well as under the lateral cortex {superpositio lateralis). On an average
the ammon-formation lies much nearer the ventricular ependyma than
the fascia dentata does, and its cells are much less numerous than those
of the latter, as is seen: (1) From the length of the ammon-formation,
compared to the length of the fascia dentata, about as 1 : in Boa

constrictor; (2) from the fact that the cells of the ammon-formation are
much less packed together. It is difficult to estimate the exact relation
between the number of granular cells and the number of pyramidal cells,
but there are at least four times more of the former than of the latter.

If we compare with this reptilian archi-cortex the archi-cortex of the
kangaroo-rat (Fig. 13) we find an enormous increas? of the ammon-forma¬
tion the length of which, compared to the length of the fascia dentata,
is about as : 2J. Moreover, the cells of the ammon-formation
(Fig. 14) are nearly as much packed together as the cells of the fascia

♦ A striking difference with the cells in the palaeo-pallium is that those in thearchi-pallium
are much further emigrated from the ventricular ependyma, and so form the beginning of a real
cortical layer.

IGG

AECHIVES

deutata (Fig. 15), and the cells of the ammon-formation extend much
nearer to the ventricle than they do in the reptiles. So, whereas in the
Boa the ammon-formation was the smaller of the two, in Hypsiprymnus
it is by far the larger, and contains more cells than the fascia. This is
accompanied by an enormous enlargement of tlie fornix and the
psalterium.

Another difEerence between the archi-cortex of reptiles and marsupials
is the large development in the latter of what in analogy to Mott’s nomen¬
clature I have called the olfacto-psychic cortex, the “ Anlage ” of the gyrus
fornicatus and the caudal subicular region, the olfactory character of
which is proved by the tertiary olfactory fibres, which reach it through
the septum* and because it receives a part of the fibrse olfacto-hippocam-
pales. The externae (tr. spheno-ammonicus) psychic, i.e., higher associa¬
tive character of this region is proved: (1) by the enormous amount of
pyramidal cells which extend into the molecular layer and so partly have
to be considered a^i supragranular pyramids; and (2) by the great number
of association fibres, which connect it with the adjoining neo-cortex and
which, with the tertiaiy' fibres above-mentioned, constitute the cingulum
S. Str. (also called cingulum gyri-fornicati, better called cingulum
limitans, because it separates the archi-cortex from the neo-cortex). This
olfacto-psychic cortex is connected with the other hemisphere by callosal
fibres and not by the psalterium.

Surveying the evolution of the archi-cortex we find as characteristic
features: —

(1) A primary prevailing of the granular layert (about four times
more granules than pyramids: Reptiles);

(2) The enormous increase in mammalia of the pyramidal layer
(ammon-formation) which has projective and bilateral associative
functions;

(3) The formation in the latter of an olfacto-psychic centre with a
great amount of pyramidal cells, which reach up to the molecular layer
and so partly have to be considered as supragranular pyramids.

It is obvious that the fascia dentata represents the granular layer of
other cortex forms, and equally sure tliat the ammon-formation repre¬
sents the subgranular pyramids and polymorphous cells, because it lies
nearer the ventricle and even partly extends under the granular fascia
dentata (c.f. fig. 4 and 13).

Comparing these results wdth Dr. Mott’s concerning the visual cortex

♦They run tojreilK-r witli the cinculum (limitans'), already pres«‘nt in reptiles, but, just
as the olfaeto psychic centre, hardly indicatetl tluTC.

t Accordinjr to J’andlt.T and Kantor this layer also a|)p‘ars first uf all the layers in the
onioircnesis of the reptilian fond)rain.

l»nYLouj:M:sis of tal^eo-coktex asd arcim-cortex

1()7

we find that the palseo, archi- and visual neo-cortex correspond in so
far as: —

(1) In the lowest degree of development the granular layer prevails in
the pafeo- and archi-cortex, and is also clearly developed in the lower
types of visual cortex;

(2) With higher development the large pyramidal and polymorph
cells, which constitute the sub-granular pyramids, become more numerous
(compare for this Dr. Mott’s drawing of a earners visual cortex with the
mole's).

(3) With further evolution, as well in the archi-cortex as in the
visual-cortex a psychic centre of higher associative character is formed in
which the granule-cells are greatly diminished, the pyramidal cells
greatly augmented, and extend unto the molecular layer* (compare for
this Dr. Mott’s description of the primate’s visual cortex with my Fig. 13).
So w'e find nearly the same principles as well in the progressive develop¬
ment of the paleeo- and archi-cortex as in the progressive evolution of
the visual neo-cortex.

In forma, however, there is a very striking difference, viz., the
fact that, while in the visual and other forms of neo-cortex the different
layers are located one above the other, they are—especially in the jarchi-
cortex—located side by side, although the pyramidal layer of the ammon-
formation is nearer the ventricle, a fact to which already Cajal and
Taalman Kip have drawn attention. The very fact that in the archi-
cortex the different layers are so far removed from each other is just the
reason why the significance of each layer can be stated there so clearly.

It seems to me that this difference may be due to the economy in
space, which is necessary in the neo-cortex, w'hich is so enormously
developed in mammals.

There is another question about which a few words might be said.

Dr. Watson, in his paper on the “ Cortex of Insectivora,” supposes
the infra-granular polymorphous layer to have, besides motor function,
an associative character of low order.

This is easily demonstrable for the sub-granular pyramids of the
archi-cortex: the ammon-formation, because we know that thepsalterium
arises here, and the psalterium, as only containing bilateral associative
fibres between two centres of the same quality (tertiary olfactory centres)
has to be regarded as a relatively low associative system.

♦ In the palaeo-cortex, the homologue of this region—as far as concerns strtctu-al
features—is found in the posterior region of the piriform lobe. The greater part of the
pyramidal cells of that region constitute fibrae-olfacto-hippocompales externat?. which are
better concerned as tertiary olfactory fibres than as associative fibres, but there end near or in
this region also cingulum limitans fibres, so the homology does not entirely fail. Moreover, we
see that this cortex continues in the subiculum and the latter in the gryrus fornicatus.

1G8

ARCHIVES

On the other hand, it is true that the anmion-formation has given rise
to the fornix and cortico-habenular tracts, and so has at the same time a
projective character. Now fornix and psalterium get nearly at the same
time their myeline-sheaths^ which is also the case with the fibres profund»
of Meynert* and the neo-cortico-fugal tracts. This, combined with the
fact that a great part of the largest pyramidal cells (Betz-cells) in the
motor-cortex, which are generally considered as mother-cells of projec¬
tion fibres, lie in the sub-granular layer, makes the above-mentioned
supposition still more probable to me: that not only in the archi-cortex,
but also in other cortices the deeper pyramids have as well a projection as
an intra-regional association function.

In contradistinction to the sub-granular pyramidal cells, those of the
supra-granular layer have a more in/er-regional associative character
connecting functionally different regions of the cortex, and, therefore,
chiefly developed in those animals which lead a more advanced intel¬
lectual life, their number being not only dependent on the development
of the special region in which they occur, but chiefly on the presence of
other neighbouring or distant cortex-regions with which they are in
connection.

This conclusion, drawn from Dr. Mott's and my own researches, has
lately been confirmed in a most striking way by a small though most
interesting article of Biny, Bing found, examining a deaf man's brain,
that there was a reduction in the cells of the auditory cortex. This reduc¬
tion, however, was almost entirely confined to the layer of infra-granular
pyramids of* which the depth was diminished to about three-fifths of the
normal (a similar observation has been described by v. Monakow after
lesion of the internal capsule). Recently, Winklerf showed me a brain of
a deaf man, which exhibited exactly tlie same features as far as concerns
its cortical layers. I believe that no fact is more able to prove the truth
of the deductions above-mentioned than these, as they confirm entirely:
(1) that the sub-granular layer depends in the first place on the local
development of the sub-cortical system to which its region belongs,
whereas the supra-granular layer is, in the first place, dependent on
iVi/6r-regional associative qualities of neighbouring and distant cortical
regions.

A few words might be added about the nature of the granular cells

♦ Interesting for the difference between deeper interradial associative fibres and the supra-
radial associative fibres (Edinger) is also Kaes’ observations (if it might prove to be constant)
that the first prevail in the Chinese and Hindoo brain, whereas the latter were more numerous
in an average European brain. It seems quite possible that “instinctive” or at least lower
associations prevail more in the first than in the latter.

t Compare: O. Brouwer, Over doofstomheid en tie acustische Canen. Inaug. dissert,
Amsterdam. 1909.

PHYLOGENESIS OF PAL.EO-CORTEX AND ARCHI-CORTEX

im

in iiie brain-cortex. They belong, as is known, to the intercalary
cells of Von Monakow, who pointed out their presence in nearly
all parts of the central nervous system. Since he called special attention
to them, their general occurrence has often been stated, and it is beyond
doubt that their presence is of utmost importance.

In a paper upon the causes of formation of nervous tracts, I have
pointed out that there are several good reasons to prove that a connection
between dilferent regions of the central nervous system is mostly caused
by the sensory qualities of these regions; that even, for instance, the
pyramidal tract of the forebrain does not descend to the spinal cord
because the motor cells in the latter want stimulation, but because there
is a functional relation between the sensory centres of the spinal cord and
a sensory centre of the telencephalon. I further called attention to the
probability that the granular cells of the central nervous system play
the greatest role in neuro-bio-taxis, because, while in projection cells
the nervous current is directly realised and led away, on the contrary, in
the granular cells with short axis cylinder forming an intricate network
the stimulation is kept within a certain region, and so this region acquires
a great importance as an attractive centre for the outgrowth of axis
cylinders and dendrites from other regions.

A fact is that the granule-cells, or cells with short axis cylinder,
are very often the primary places which receive the long ascending* or
descending! tracts. The phylogenesis of the palseo- and archi-cortex
demonstrates this law in a very striking way, as it shows that the small
granule-cells in the cortex are ahvays the first thing present, they are the
primary constituent of every cortex, tlie receptory cells whereabout the
long afferent (tertiary) tracts end (see Fig. 1). So, being primary in
character, they are often present in a fairly large number even there,
where their function for transmission of the nervous current on projection
cells is not yet of great importance. A striking example of this is the
fact mentioned by Zuckerkandl that in the dolphin, where no olfactory
tracts are present the fascia dentata forms a “ thick layer ’’ of cells, and
equally interesting is the fact that in the visual cortex of the mole, a
nearly blind animal, the granular layer shows the best development.
The same was the case in the deaf man’s brain examined by WtnMer,
where the granule-cells did not show any reduction at all.

The efferent tracts and their cells, according to my results about the
palaBO- and archi-cortex, are formed only later, and no doubt they

• A striking; example is the ending of the sensory root-fibres in the oldongata and (less
general) in the coni.

t A striking examfde is the en<ling of the pyramids in the eord and of the tecto-bulbar
tracts in the oblongata.

iro

AECHIVES

take tlieir origin from undifferentiated cells, which originally in their
form and character come nearer the granules. An example of this seems
to be given by the primordium hippocampi of Amphibia, where some
cells, of which the perikaryon and the dendrites are exactly like those
of granular cells, send out pretty long axis-cylinders, which pass in the
commissura pallii to the other side.

From this point of view it is not astonishing if, during phylogenesis,
we should not only find an augmentation of the pyramidal cells, but also
a diminution of the granule cells in certain regions.

The latter cannot easily be stated in the archi-cortex, because the
numbers above-mentioned, which show the relation between the granule
cells and pyramidal cells in the archi-cortex of reptiles and mammals,
may be due as well to an augmentation of the pyramidal cells alone
(which, in this case, I think more probable) as to an augmentation of the
latter and a diminution of the granule cells at the same time.

The phylogenesis of the palseo-cortex, however, supports this mode
of evolution if we compare Fig. 1 to Fig. 4, where not only the augmenta¬
tion of pyramidal cells is visible, but the diminution of granule cells is
still more evident, and although in marsupials the granular-like layer
in the fronto-basal })art of this cortex is still very large, there are cer¬
tainly much less than in the Selachian palseo-cortex, so that there really
seems to be some evidence for the supposition that not only the augmenta¬
tion of pyramidal cells, but also diminution of granule cells,
at least in some regions, may be an attribute of further development
during phylogenesis, a conclusion which seems to be in harmony with
Brodmann’s ontogenetic observations, though certainly in other regions
further development is accompanied with an augmentation of the
granules.

There i^ still anotluu’ j)()int about these intercalating cells to which
attention may be drawn; the fact that these little granule-cells are
sometimes pn^sent, where two long paths join, without being interca¬
lated betwe(Mi the paths. An example of the latter is the formatio
bulbaris, wlnue granule cells can be found from the cyclostomes
(Johnston) to the mammals, whereas the dendrites of the mitral-cells in
the glomeruli olfactivi are in direct contact with the end branches of the
fila olfactiva.

Apparently there are j^laces where such an intercalation between the
afferent and efferent tracts is either not necessary, and never has existed,
or has gradually disappeared. This much is certain, that there are
jdaces where tin* granule-cells are nearly always intercalated between
two long tracts (as f.i. between the sensory and motor-root of the VII.,

PIIYLOGENESJS OF rAL.EO-CORTEX AND AECHI-CORTEX

171

and between the sensory root of the IX. and X. and the nucl. ambiguus)
and others (less in number) where they are not present as such.

Without presuming to be able to explain this difference, I desire to
call attention to it, inasmuch as in the progressive development of the
palseo-cortex we observe something analogous in the fact that not all the
secondary olfactory fibres end around cells with short axis cylinders,
which, as already pointed out, may be the case in a part of the archi-
cortex.

It is uot improbable that, in a region wliere the granules were
originally abundant, in the course of progressive evolution they may
change into larger stellate or pyramidal cells of projection systems. If
their axis cylinder became longer* their cell-body also would lose the
small granular form, and then the afferent tracts would terminate directly
around a projection cell. Similar results have been obtained by Dr.
Itondoni, who worked in Dr. H. Vogt’s department of Edinger’s Institute,
on j)athological brains.

On the other band, it might also happen that, when in a certain
region of the central nervous system only one direction in the nervous
current is possible, as in the bulbar formation, where associations with
other regions are excluded, that a direct connection without intercalation
is formed and the granular cells only form short paths of association
between adjacent cells.

With our present knowledge, however, of the structural laws of the
nervous system, this question cannot yet be explained with certainty, and
the idea of this short communication is chiefly to point out the evolu¬
tionary principles of the palseo- and archi-cortex, their resemblance with
those in the progressive evolution of the visual neo-cortex, as shown by
Dr. Mott’s work, and the character of the different cortical layers, which
we may deduce from them.

Resuming my results, I may draw the following conclusions: —

(1) The granular layer in the cortex is primary in character, and has
originally receptory functions. This can be proved phylogenetically and
pathologically. Being primary in character, it shows a great constancy
ill being present, whether the affeient fibres are numerous or not. (It
can enlarge, however, if the afferent tracts greatly increase.)

(2) The infra-granular layer, as already pointed out by Watson, has
projection and intra-regional associative functions.! It increases phylo-

An example of this is seen in the development ot the secondai v epistrialnm whicli in
palaio-cortex, and so has very short ^nnections with i"
whereas in mammals the same conmctions (with the nuelcus amv-gdahe) are very much longer’

amouUoi^ffrr^nrfibr^^alt^^ do receive) a certain

172

AtCHlVES

genetically after the formation of the granular layer and before the
formation of the supra-granular pyramids [Mott).

(3) The supra-granular pyramids—as already was proved by Dr. Mott
are the latest to appear—have chiefly associative functions of a higher
order,* and, therefore, are just as much dependent on the surrounding
regions as on the region where they are found. This can be proved phylo-
genetically and also pathologically, as they remain very much the same
after localised sub-cortical lesions.

(4) The first tactile neo-cortical centre (occurring in Reptiles) belongs
to the trigeminal sensibility. This has to be explained by the associative
functions between olfactorium and oral sensibility.

(5) The neo-cortex originates from the paleeo-cortex, and not from
the archi-cortex. This explains why the corpus callosum (commissure of
the neo-cortex) in the lower mammals originally runs ventrally together
with the anterior commissure (commissure of the palaeo-cortex), and not
dorsally with the psalterium (commissure of the archi-cortex).

* So(* note nniler t on jnwious |»a<ro.

LITERATURE :

Mott, F. W. “ The progres-sive Evolution of the Structure and Functions of the
Visual Cortex in Mammalia,** Archives of Neurology^ vol. iii., 1907 (London).

Watson, G. A. “The Mammalian Cerebral Cortex, with special reference to its
Comparative Histology. 1. Order Insectivora,” uirchives of Neurology^ vol iii.,
1907 (London).

EDINGER, L. “Vorlesungeu iiber den Hau der nervbsen Centralorgane des Menschen
und der Thiere,” 2ter Band, 7te Auflage, 1904.

Edinger, L. “ Neue Studien uber das Vorderhirn der Reptilien.” Abhandlungen
der Senckenbergischen Naturforschenden Gesellschaft in Frankfurt a. M., 1896.

Brill, N. E. “The true Homology of the Mesial Portion of the Hemispheric Ve.sicle
in Sauropsida,** Medical Review, March, 1890.

V. Monakow, C. “ Himpathologie, Holder, Wien,” 2te Auflage, 190o.

Called A. La region olfatoria del cerebro. Madrid, 189.3.

Ramon y Cajal, S. “ Textura del Sistema nervioso del Hombre y de los Yerte-
brados,” Tome ii., Moya. Madrid, 1904.

Brodma.x.v, K. “ Beitriige zur histologi.scheii Localisation der Grosshimrinde.
Fiinfte Mittheilung,” Jonnud fur Neurologic und Psyrltologie, Band vi., 1906.

Levi, Gius. “ Sull’ origine filogenetica della formazione ammonica,” Archirio di
Anatamia e di Emhriologia, vol. iii., 1904.

Unger, L. “ Un ter such un gen ul)cr die Morphologie und Fascrung des Reptilien-
Gehima,*’ A jiat. Hcfie, Band 31, 1906.

Taalman, Kip. “ De Phylogenie van de Cortex Cerebri.” Verhandelingen van het
negen-de Vlaamsche Congre.s voor Natuur- en Geneeskunde, 1905.

PLATE I.

Fig. 1.

A part of the palseo-cortex of ScyIlium caniciila

Fig 2.

Celia of the graiiul:ir
layer of the palaeo-cortex
of ScyUium canicula

V'

Fig. .‘1.

Cells of the infragranular layer of the pahieo-cortex
of ScyUium caiiicula.

p. 172.

PLATK II.

Fig. 4.

The pallium of boa constrictor.

A is the fascia dentata.

B is the ammon formation.

C is the lateral cortex, which originally represents the palmo-cortex, but here
already includes the first rudiment of Neo-cortex, and dor.-<ally a small
associative group of cells.

Fig. 5.

Cells of the upi>er part of the lateral cortex of boa constrictor.

* K

Face p. 172.‘

Fig. G.

Cells of the fronto-basal part of the paheo-cortcx of boa constrictor.

PLATE III.

Ei(». 7.

Occipital pole of the brain of Hypsiprymnus rufescens (where the
palreo-cortex and nrchi-cortex meet).

i;

*4*

/

.// ^

• l • K V ^ i . / f' '

V‘*.'• V <

t

' \

' A^

Fig. 9.

Orainila-like cells in the
front o-basal i)art of the
paheo-cortex of Hypsipryui-
mis rufescens.

Fig. c<.

Ficuto-basal part of the paliocortex of Iljpsiprymnns
rufesceno.

hnvp p. 172 .

Fig. 10 .

Pyramidal infragranular cells
in the fronto-basal p.art of the
pal neo-cortex of Hypsiprymnus
rufescens.

PLATE IV.

/

•3

Fig. 11.

Granule cells in the fascia
dentata of Ijoa constrictor.

Fig. 12.

Pyramidal cells in the ammon formation of boa constrictor.

.V. ,©• »

y Cd

/

O

V

Fig. 15.

Grannie cells in the fascia dentata

Fig. 14.—Pyramidal cells in the ammon formation of Hypsipr>mniis rufcscen...

llypsiprymnus mfescens.

Face p. 172,

PHYLOGENESIS OF PAL^O-CORTEX AND ARCHI-CORTEX

173

Tandler, J. und Kantor, H. “ Die Entwickelungsgeschichte des Gecko-Gehims,”
Anai. Hefte, Band 33, 1907.

Kaes, Th. “ Ueber Grosshirnrindenmasse, und iiber Anordnung der Markfaser-
systeme in der Rinde des Menschen, u.s.w.,” Wiener Medizinische Wochenschrift,
45, 1895.

Kaes, Th. “Ueber Markfasergehalt der Hirnrinde,” Miriichener Medizinische Wochen-
schrift, 43, 1896.

Johnston, J. B. “The Nervous System of Vertebrates,”?. Blakiston’s, Sou & Co.,
Philadelphia, 1906.

Livini, F. “ II Proencefalo d’un Marsupiale,” Archivio di Anaimnui e di Emhriologuiy
vol. vii., 1908.

Ariens Kafpers, C. U. und Theunissen, W. F. “ Die Phylogenese des Rhinen-
cephalons, des Corpus Striatum und der Vorderhim-Commissuren,” Folia
Neurohiologica, Bnd. i.. Heft ii., 1908.

Ariens Kappers, C. U. “ Weitere Mittheilungen iiber Neuro-bio-taxis.” Folia
Neurohiologica, Bnd. i., Heft iv., 1908.

Haller, B. “Die phyletisohe Entfaltung der Grosshimrinde,” Archiv. f. Mikro-
akopische Anatomie, Bnd. 71, 1908.

Rondoni, P. “ Contribute alia Patologia dello Sviluppo del Cervello,” Archivio di
Biologia normale e paiologica. Anno Ixii., Fasc. iii., Maggio-Giugno, 1908.

Vogt, H., und Rondoni, P. “ Zum Aufban der Hirnrinde.” Deutsche unediziniache
Wochenachrift, No. 44. 1908.

Siebenmann, F., und Bing, R. “Ueber den Labyrinth und Him. befuiid boi eifiem,
an Retinitis pigmentosa erblindeten Angeboren-Taubs turn men,” Zeiischrifi f.
Ohrenheilkunde, Bnd. 57, Heft. iii. und iv.

Brouwer, “ Over doofstomheid en de acustische Caneu.” Inaug. Dissert., Amster¬
dam, 1909.

174

A CHEMICAL STUDY OE THE DRAIN IN HEALTHY AND
DISEASED CONDITIONS, WITH ESPECIAL REFERENCE
TO DEMENTIA PR^COX.

Bv WALDEMAR KOCH am> SYDNEY A. MANN.

(From ihr Pathohtqxral Tjnhorofort/ of the LunuUm (bonify Asyhnm ond thr IfuU
Jdiy»iolo(jn'a/ Jjahurotory of thr Foirrrsify of Chirotfo.)

CONTENTS.

SECTION I.—LvTHonrcTiON.

Aiiiilysis of I^riiie
Anjilysis of Ct*rel>rosj)iiial Fluid
Examination of Nerve l^issue ...

Chemical Comstituents of Brain Ti.'^sue
Brinciples of Estimation of (M)nstituents

SECTION Tl.—E xpeiumkntal Part .

Oeneral Outline of Methods
Collection and Preservation of Material
Method of Extraction ...

Details of Method
Separation of Lipoids ...

Estimation of Sul])hur ...

Method of Keeping Analytical Records and Calculation
Estimation of Phosphorus
Estimation of Water
PiStimation of Groups of Constituents

SECTION Til.— Analytical Results .

Comparison of Brains at Different Ages
Com])arison of Th-ains from Different Sj)eci(‘s
Comparison of Brains from Cas(‘s Dying of Diffeieiit Can
Changes observed in Mental ('ases ...

(e) Dementia Prcecox
(h) Dementia Paralytica ,

(/•) Other Cases of Mental Disorder
Changes observed as the Result of Expeiimental Pr
Dr. F. H. Pike) .

SECTION TV.— Desciuttion of Ca.ses .

SECTION V.— Summary .

ReFEKENC'ES .

of Res

lilt

edii

(w

th

Pa OB

175
175
175
175
I7t>-180
ISO-IS-J

182

182.183

183-185

185-188

189-191

191- 192

192- 190
196-198
198-200
200-201
201-202

202

20L-205

205- 206
206
206

206- 209
209-210

211

211-212

212-216

216-218

218-219

CHEMICAL EXAMINATION OT BRAIN

175

I.—In trod u ction .

At the suggestion of Dr. F. W. Mott, F.ii.S., the methods for the
chemical study of the brain outlined in a previous paper (1) by one of us
(W. K.) have been extended to the study of certain mental disorders.
In the course of the work the above methods have been frequently revised
and elaborated, and we take this opportunity of republishing them in
their amended form.

Attempts have been made by various observers to study the chemistry
of mental disorders by analysis of the various bodily fluids and
excretions, such as the blood, cerebrospinal fluid and urine. Results
obtained by this method are difficult of interpretation and are liable to
lead to erroneous conclusions. With regard to the examination of the
urine, Folin and Schaffer (2), using carefully elaborated analytical
methods, have completed an exhaustive work, and have come to the con¬
clusion that there is little information to be obtained by attacking the
problem solely through tliis source, and, further, that the large number
of observations on record based on analysis of the urine and regarding
the relation of an abnormal metabolism of tlie body to mental derange¬
ment, are of little value. The more recent observation of Pighini
[Vide p. 220), that there is an increase of neutral sulphur in the urine in
dementia praecox can be explained as being due to a general decrease in
the oxidations and can be produced experimentally, as Richards and
Wallace (0) have shown, by cyanide poisoning. This result, however, is
of interest in view of the change in the neutral sulphur content of the
brain ( Vide p. 209) in this form of mental disorder.

The cerebrospinal fluid bears a more direct relationship to the nervous
system and offers good opportunities for the chemical study of the pro¬
ducts of nervous metabolism, but the amount of fluid which can be
safely withdrawn by lumber puncture during life is not sufficient to
allow of accurate quantitative estimations. Qualitative tests, however,
have shown in certain morbid conditions the presence of various products
of degeneration, r.^., choline (Mott and Halliburton (4) ), and in general
paralysis especially, a disease in which the fluid is in great excess, the
protein and lipoid constituents are found to be increased in amount.
In view of the significance which has been attached to the Wassermann
Plant reaction in cases of general paralysis and other parasyphilitic
aft'ections, the further studj- of the protein and lipoid constituents in
the serum and cerebrospinal fluid of these cases is of great importance
in deciding the chemical nature of the substance causing the complement
deviation.

Eitamination of the nerve lisstte —(a) Micro-chemical .—By far the

176

ARCHIVES

largest number of investigations of the nervous system itself have been
concerned with such histological methods of staining as devised by
Weigert, Nissl, Golgi, Eamon y Cajal, Held, and others. These investi¬
gations have shed light on the anatomical structure of the Brain, but on
account of our great lack of knowledge of the chemical constituents of
the nervous system which are involved in these reactions, comparatively
few have been regarded in the light of micro-chemical reactions. Gustav
Mann (5), in his excellent text-book of physiological histology has stated
practically all that can be said on the subject. Micro-chemical methods
may decide points of anatomical distribution of constituents in a qualita¬
tive manner and correlated with quantitative macro-chemical observa¬
tions lead to important conclusions. Thus in two cases of amaurotic
dementia Mott (6) was able to associate the disappearance of the Nissl
substance in the neurons with a decrease in nucleo-proteid, and an
increase of the glia fibrils with an increase of simple proteid, the brain
in each case being chemically examined by one of us (S. A. M.).

Examination of the nervous system —(b) Macro-chemical ,—The study of
the quantitative variations in the composition of the brain under normal
and pathological conditions has so far received but little attention. In
fact, this may be said of any tissue of the body on iiccount of our lack of
knowledge of the substances to be estimated. Our present knowledge
permits us only to refer to groups of substances which in the nervous
system may be arranged under the following general headings: —

1. Lipoids.—Phosphatids, cerebrins, cholesterin, and a sulphur com¬
pound.

2. Extractives.—Organic water soluble compouiids not colloidal in
nature, e,q,^ kreatin, taurin, hypoxanthin, etc.

3. Inorganic constituents.—Ash.

4. Proteins.—Nucleoproteins, globulins, neurokeratin.

A more detailed account of the chemical constituents isolated from
the brain was given in the 1904 paper, and for the sake of completeness
it is here brought up to date.

Chemical Constituents of Brain Tissue.

1. Water.— HgO, present in largest amount.

2. Simple and Compound Proteins (C, H, O, N, S, P).

Globulin coagulating at 47^-50^ C. (Halliburton (7)).

Globulin coagulating at 70^ C. (Halliburton (7) ).

NeuTostromin (Schkarin (8) ).—Extracted by sodium hydrate, present
only in small amount.

CHEMICAL EXAMINATION OF JmAIN

177

Nucleoprotein (Levene (9)).—Contains 0*57 per cent, phosphorus. The
nucleoalbumin .of Halliburton (7) and the neuroglobulin of Schkarin (8)
may be considered to be identical or closely related to the compound
isolated by Levene.

Neurokeratin (Kuhne and Chittenden (10)).—An albuminoid insoluble
in sodium hydrate and not digested by ferments.

3. Extbactives (water soluble) (C, H, 0, N, P, S).

Hypoxanthin, —C^H^N^O (Thudichum (11), p. 319).

Tyrosin, —C^H^^NOg (trace) (Thudichum (11), p. 330).

Leucin, —CgH^3N02 (trace) (Thudichum (11), p. 332). Both evidently
derived from post-mortem decomposition.

Urea. —CH^NgO (Gulewitsch (12)): its presence is not due to con¬
tamination with blood (essential constituent).

Peptones and alhumoses. —(Thiidichum (11), pp. 316 317) considers the
osmazon of the French chemists to be closely related to this group.

Sarcolactic add (Thudichum (11), p. 317).

Formic^ acetic^ sucdnic^ and lactic acids (Thudichum (11), p. 329).—May
be considered to be derived from j^ost-mortem decomposition.

Inosit. —CgH,20g2H20 (Thudichum (11), p. 319). The presence of
this substance has been confirmed by a number of investigators.

Taurin or some immediate antecedent (Koch (13)).

Kreatin. —C^H^NgO.. found to be present by the method of Grindley

( 28 ).

Besides the above-mentioned substances, the following have been
occasionally found to be present under pathological conditions by various
authors, and must be considered on account of introducing sources of
error in the methods of determination, especially with pathological
material; they are: Neuridin (Brieger (14)), uric acid (Thudichum (11),
p. 318); choline (Mott and Halliburton (5) ) also, according to Gulewitsch
(12), present as a normal constituent; triraethylamine (Thudichum (11),
p. 330), evidently the result of post-mortem change.

4. Inorganic Constituents.

Ka, K, NH^, Ca, Mg, Fe, present partly as dissociated ions, and
partly in organic combination. •

5. Phosphatids (C, H, 0, N, P).

Lecithins. —Stearyloleyl lecithin, C^^HggNPO^'OH,

Margeryloleyl lecithin, C^jHg^NPOg'OH,

Palmityloleyl lecithin, C^jHg^NPOg'OH,
isolated as a mixture of isomers and homologues by Thudichum (11, pp.
322, 123) and Koch (15), are all characterised by the presence of three
methyl groups attached to nitrogen. One methyl group splits ofE quan-

M

178

AECHIVES

litatively at 240® C. with hydriodie acid, the remaining split ofE at
;500® C. These lecithins have basic properties, form double salts with
cadmium cJiloride, but do not form insoluble lead salts. They are soluble
in alcohol and ether. Phosphorus, 4 per cent.; nitrogen, 18 per cent
Proportion 1:1.

— Amidomyelin, C^^Hg^N^PO^. Isolated so far only
by Thudichum (11, pp. 322, 123, 110), who has not published complete
analyses. From the empirical formula, this substance evidently is
closely allied to the lecithins, and should have three methyls attached to
nitrogen. The quantitative results indicate that this substance can be
present only in extremely small amount. Nitrogen, 3*5 per cent.; phos¬
phorus to nitrogen as 1:2.

Kephalins : —

Kephalin, (Thudichum (11), pp. 320, 130; Koch

(15)).

Oxykephalin, C^jH^^NPOj^ (Thudichum (11), p. 138).

Peroxykephalin, C^gHygNPOj^ (Thudichum (11), p. 138).

Myelin, C^gH^gNPO^g (Thudichum (11), pp. 323, 156).

These substances are derived from the lecithins by the loss of two methyl
groups and an oxidation of the oleic acid radicle, the chemistry of which
is very obscure. In consequence of the nitrogen becoming a triad, the
basic properties are lost, and these substances consequently give insoluble
lead salts. The methyl group is split off quantitatively at 240® C. with
hydriodie acid. No more methyl is split oft‘ above that temperature. A

comparison of the formula makes it evident that kephalin . is

derived from stearyloleyl lecithin . and myelin . from

palmityloleyl lecithin . These substances are soluble in ether,

insoluble in alcohol. Phosphorus, 3*7 per cent.; nitrogen, 1*7 per cent.
Proportion of 1:1.

Aitiidokephnlins. —Amidokephalin, C 42 HgyN 2 POj 3 . Isolated so far
only by Tliudichum (11, p. 107), may be considered to be derived from
tlie amidomyelin by the loss of two methyl groups and an oxidation
similar to kephalin. The empirical formulte support this theory. Phos¬
phorus to nitrogen as 1:2.

Besides the above-mentioned, the following compounds, whicli are
difficult to classify, have been isolated by Thudichum :— Paramyelin,
CggH^.NPOg, pTobu61 v related to lecithin. Sphinnomydin,

NjPO^, recently confirmed by Rosenheim (39), probably related to the
amidolecithins (nitrogen 3 per cent.), containing however, no glycerine.
Assurin, (Phosphorus 7 per cent.; nitrogen 3*2 percent.).

6. Cerebrtxs (C, H, 0, N).

Within recent years these substances have been studied on human

CUEUICAL EXAMINATION OF UBAIN

179

material by Thudichum (11, p. 178) and Thierfelder (16), on sheep’s
brains by Koch (15), and on horses’ brains by Bethe (17, p. 78), and more
recently confirmed by Rosenheim. As there is very little difference in the
cerebrins derived from different species it will simplify matters to compare
them regardless of their source.

Phrenosiny The substance isolated by Thudichum

(11, p. 184) may be said to be identical or isomeric witli that isolated by
Thierfelder and by Koch, as will be seen from a comparison of the
analyses: —

Thudichum.

Thierfelder

Koch.

Carbon ...

... 69*00

tisie .

68*73

Hydrogen

... 11*08

11-.54

11*83

Nitrogen

... 1*96

1*76

1*64

Phrenosin spits oft' galactose on heating with dilute mineral acids.

Kerasin, C 44 HggNOg (Thudichum (11), p. 218), probably identical
with Bethe’s (17, p. 184) amidocerebrin acid ghjcosidy C^^Hg^NOg.
Both are undoubtedly homologues of phrenosin, and in the same way
split off galactose.

Phreniriy isolated by Bethe (17, p. 184), was obtained by Koch as a
decomposition product from cerebrin after boiling with dilute hydro¬
chloric acid. The analyses agree fairly well.

Bethe. Kocb.

Carbon ... ... ... ... 71*90 . 71*00

Hydrogen ... ... ... 11*95 . 12*14

l*^it^ogen . 1*5 . 1*89

This substance does not split off a reducing sugar as do phrenosin and
kerasin.

Cerebrin acids so far only isolated by Thudichum (11, p. 221).

Cerebrin acid, and spJuerocerebrin, C^gHjggXOjy, are

characterised by forming lead salts insoluble in hot alcohol. This dis¬
tinguishes them from kerasin and phrenosin, which do not combine with
lead. Cerebrin acid, according to Thudichum, splits off galactose. A
comparison of the percentage of carbon found by Thudichum makes it
extremely probable that these substances are intermediary oxidation
products of phrenosin and kerasin, as indicated by the following
figures: —

Phren(ksin. Cerebrin Acid. SrH.ERocEREBRiN.

Carbon. 69*0 . 67*00 . 62*75

Hydroceu ... 11*08 . 11*36 . 11*08

Nitrogen ... 1*96 . 1*59 . 1*23

No other substances have been isolated which may be said to belong
to the group of the cerebrins. The cerebrinphosphoric acid of Bethe is

u 2

180

ARCHIVES

only an impure mixture which undoubtedly contains sulphur, for which
he neglected to test. None of the members of this group can be said to
be pure until they are free from sulphur and phosphorus, both of which
elements cling to them most tenaciously. All the cerebrins when pure
are insoluble in ether and soluble in hot alcohol. The cerebrin acids are
more soluble in glacial acetic acid than phrenosin.

7. Cholesterin (C, 0, H), occurs in the brain as free

cholesterin and not in the form of esters. Soluble in hot alcohol and
cold ether. Biinz (18). Tebb (19).

8. Sulphur Compounds (C, H, O, N, P, S). —Thudichum (11, p. 224),
Koch (13).

9. Amidofats (C, H, N, 0).

Krinosiriy CjgHy^NOg.

Bregeniriy Cg^Hg^NOg.

These substances have so far been only isolated by Thudichum (11,
p. 227). They are distinguished from fats by their insolubility in ether.
The quantitative determinations indicate that they may be present in
small amount only. They most probably represent post-mortem decom¬
position products.

10. Monophosphatids (C, H, 0, P).

lApophosphoric acidy Jndophosphoric acid, —Isolated by Thudichum
(11, p. 177), but not analysed completely. Contain about 4 per cent, of
phosphorus, and are free from nitrogen. May be present in slight amount
in white matter, as not quite all the phosphorus is accounted for. Most
probably, however, they are either post-mortem decomposition products
or the result of chemical manipulation.

This completes the list of substances isolated or supposed to have been
isolated from brain tissues. Free fats and fatty acids have never been
found to be present in normal brain tissue. Bethe (17, p. 86) mentions
stearic acid but adds a question mark, which is a wise provision, as he
has been rather unfortunate in describing decomposition products as
primary constituents (phrenin, see above), Protagon we have no intention
in resurrecting, in spite of fears to the contraiy (20), as the work of
Thierfelder (16), Gies (21), and Eosenheim and Tebb (22) has settled its
fate. For further discussion on this subject, see also Cramer (23, 24).

Principles of estimation of constituents, —These constituents are
separated into the four general groups mentioned above (p. 176) by
solvents according to the following outline: Alcohol has proved
to be the most satisfactory solvent, and, although it is desirable
in a quantitative study of this kind to rely on methods of separation
by solvents as little as possible, observations which are recorded later

toEMiCAL EXAMliJATlON BRAE^

l8l

(p. 188), indicate that the separation of lipoids from the proteins is as
good as can be found at present.

Moist Tissue.

Add alcohol and extract alternatelj with alcohol and ether.

EXTRACTS. H ESI DUE.

Evap. to dryness, emulsify with w^ater ])pt. Dry, weigh, extract with hot w^ater.

with chloroform in 0.5 HCl solution.

(1) Lipoids.
Phosphatids.
Cerebrins
Cholesterin
S. Compound.

(2) FILTRATE.

Water soluble
extractives.

Inorganic consti¬
tuents (ash) also
the group Sj, P^
(see later).

(;l) FILTRATE.

Water soluble
extractives.

Inorgjinic consti¬
tuents (ash), also
the group Pj
(see later).

(4) RESIDUE.
Proteins.

N ucleo-protcMTis.

Besides studying the variations of the constituents as cerebrin, protein,
which may be looked upon as the food supply of the brain, in normal
and pathological cases, the variations of the distribution of the elements
phosphorus and sulphur among the various groups were also investigated.
The selection of these two elements was based on the following con¬
siderations.

Phosphorus occurs in the body exclusively as combinations of phos¬
phoric acid, an oxidised derivative. Its mechanism of absorption and
intermediary metabolism is not yet fully understood, but it is quite
certain that it enters the system either as a phosphate or some simple
organic derivative and leaves in the form of an acid phosphate. It is
the radicle which seems to play the role in the building up of the most
complex constituents of the cell, the nucleins and phosphatids. The
variation in its distribution between these and the water soluble extrac¬
tives should therefore give an indication of the amount of destruction of
these important cell constituents. The following outline will serve to
make this clear: —

Nucleins

Organic combinations of —
phosphoric acid. —

(Water soluble.)

ti

Phosphates.

Lecithins

A relative increase of the water soluble phosphoric acid derivatives may
be interpreted as being due to an excessive breakdown of nucleins and
lecithins, or may occur during a condition of rapid growth where the
food materials are supplied in abundance (25). During a condition of
starvation, where, however, the reparative reaction is still going on,
phosphates should be decreased (26).

182

ARailVES

Sulphur occurs in the body in various stages of oxidation. As —SH

o

or cystin sulphur in proteins, as sulphonate or r-s-oh or taurin like

o

sulphur, and as ethereal and inorganic sulphates. Sulphur probably
enters the organism largely as unoxidised or cystin sulphur and leaves
to the extent of 95 per cent, in an oxidised form as inorganic sulphates.
It differs, therefore, from phosphorus in undergoing a change in its
state of oxidation as a result of the intermediary metabolism. It seemed
possible, therefore, to utilise the variation in the different stages of
oxidation of sulphur for measuring the extent to which oxidising
reactions are going on in the tissues, especially as the work of Heffner
(27) shows that the affinity of the sulphur group for oxygen plays a very
important r61e in the organism. The relations are made plain by the
following scheme: —

NH^

NHa 0

R—A—1— OH — ►

0

R_0—Lori

0

ho-Loh

1

R_C-S —>

1

J »

II

II

R_C—S

1

H u

o

0

1

Nfl^

Neutral or

Ethereal sulphate

Sulphates*

Protein S

Taurin S

Lipoid S

II. —Experimental Part.

Methods ,—Before entering into the details of the methods adopted,
we consider that it will save the reader much confusion if we state in
full the symbols by which we have designated the various sulphur and
phosphorus fractions. Incidentally, we put this forward as a system
of labelling, for it must be remembered that the examination of one brain
lasts nearly one month, also the various fractions are constantly being
transferred from one vessel to another, and when a few brains are being
examined at the same time, a definite system of labelling must be
adhered to.

The general scheme of separation then leads to four fractions: —

1. Alcohol soluble, insoluble in acid chloroform water (lipoids).

2. Alcohol soluble, soluble in acid chloroform water (extractives).

3. Alcohol insoluble, water soluble (extractives).

4. Alcohol insoluble, water insoluble (proteins).

It is in these various fractions that it is proposed to study the distri-

CIIKMICAL EXAMINATION ot BRAIN

183

butions of the elements sulphur and phosphorus. These various fractions
may then be designated : —

Si. Alcohol soluble, acid chloroform water insoluble, lipoid sulphur.

Sg. Alcohol soluble, acid chloroform water soluble, extractive sulphur.

S 3 . Alcohol insoluble, water soluble, extractive sulphur.

S^. Alcohol insoluble, water insoluble, protein sulphur.

SJ and Si represent inorganic sulphates, derived from these fractions
by direct treatment with barium chloride.

The same applies to the phosjihorus fractions.

Pj. Alcohol soluble, acid chloroform water insoluble, lipoid phos¬
phorus.

Pj. Alcohol soluble, acid chloroform water soluble, extractive phos¬
phorus.

Pj. Alcohol insoluble, water soluble, extractive phosphorus.

P^. Alcohol insoluble, water insoluble, protein phosphorus.

Pi and PJ represent inorganic phosphates derived from these fmctions
by direct precipitation with magnesia mixture.

Pi' and Pf represent lecithin and kephalin phosphorus as separated
by the lead kephalin salt.

Such a system of notation is of great value in a large number of
analyses. By adding the case number it is possible to tell after several
months just how the material has been handled. Thus 23 Pj* x 5 refers
to sample 23 and means the lecithin fraction of the total lipoid phos¬
phorus multiplied by 5 on account of the fact than an aliquot part was
taken. 70 S 3 means that in sample 70 the hot-water extract of the
alcohol insoluble residue was precipitated direct with barium chloride
in hydrochloric acid solution.

Collection and Preservation of Material.

The previous method of collecting the material by separation of the
grey and white matter was only followed in a few cases, which will be
given later. It soon became evident that, especially in the case of the
grey matter, too much time would be required to collect the amount of
material necessary to ensure accurate analyses in some of the sulphur
and phosphorus fractions. As changes in the metabolism of the nervous
system such as we are here seeking to investigate are more apt to affect
the brain as a whole, it seemed advisable to take larger samples, and
one half of the brain was used for chemical work and the other retained
for histological examination.

The half of the brain intended for chemical work can be used either
as a whole or for the separation of the cortex and corpus callosum. Tlie
membranes are removed and any blood washed away, and the brain

184

ARCHIVES

allowed to drain. This procedure vitiates any absolute estimation of
the amount of moisture, but as this figure was never used except to refer
the constituents to the per cent, of total solids, there is no error involved.

(a) Collection of white matter from corims callosum and adjacent centrum
ovale ,—As much as possible of the corpus callosum and centrum ovale
is dissected and all adhering particles of grey matter removed. It is
then finely minced with scalpels and a two-gramme sample taken for
the moisture determination. The remainder (50 grammes) is transferred
to a 250 c.c. bottle and weighed. Absolute alcohol is added to nearly
fill the bottle and the whole is well shaken. The following day the
bottle is again shaken, heated to 75° C. by immersion in water at that
temperature, and set aside for future analysis.

(b) Collection of grey matter from cortex ,—The frontal and motor
regions are utilised and the grey matter is trimmed off with a sharp
scalpel without any adhering white matter. About 50 grammes of
cortex is collected in this manner, minced, and mixed as well as possible,
two grammes taken for the water estimation, and the remainder weighed
and preserved the same as the corpus callosum. This mode of collecting
the grey matter takes a considerable time, and requires much care and
patience.

(c) Collection of mixture of grey and white matter from the whole
hemisphere ,—The whole of one hemisphere is passed through a mincing
machine with a fairly fine wire mesh (i-inch), well mixed and again
passed through the mincing machine, and three one-hundred-gramme
samples taken. A sample this size ensures a sufficiently uniform mixture
of the white and grey matter {vide p. 200), and gives amounts of barium
sulphate and magnesium pyrophosphate in the various sulphur and
phosphorus fractions large enough to give accurate weighings, and does
not involve the extraction and destruction of inconveniently large amounts
of organic material. The three lOO-gramme samples are preserved in at
least 400 c.c. of absolute alcohol each; allowing for the amount of
moisture in the sample, this ensures a concentration of about 83 per cent,
alcohol in the preserving fluid.

As some of the samples were analysed at different periods of time
after the collection of the material, it seems of interest to compare them

from the point of view of this method of

preservation : —

Time between collection and

analysis of sample ...

3 hours

2 (la vs

2 weeks

3 months

Sulphur in alcohol soluble
fraction

427

38-4

36*9

35*9

Sulphur in alcohol insoluble
fraction

37-3

(317

63-1

641

Phosphorus in alcohol soluble

fraction

8f)-3

87‘0

847

83-8

Phosphorus in alcohol in-

soluble fraction

13-8

12-5

15-3

16-3

CHEMICAL EXAMINATION OF BKAIN

185

The changes to be observed in the sulphur are evidently not due to
lack of preservation, but indicate rather an incomplete coagulation of the
proteins. After two or three weeks this coagulation seems to be complete,
and the results then are more uniform. It is well, however, on the day
after collecting the sample to thoroughly shake up the mixture so as to
ensure complete penetration of the alcohol into the tissue, and to heat it
up to a temperature just below the boiling point of alcohol by placing
the bottle containing the sample in a water bath at 75^ C.

One other factor needs to be considered in the collection of the
material, i.r., the amount of variation introduced by the time the material
is kept after death before preservation in alcohol. It is quite impossible
to avoid the immediate post-mortem changes which occur at the moment
of cell death or possibly just before; but as the hospital and asylum
brains were handled in much the same way this variation becomes
constant. The differences between a brain collected one hour or thirty
hours after death, how^ever, need to be considered. As the differences are
apt to take the form of autolysis or breaking up of the complex colloidal
molecules into simpler ones they would influence the relation of the
different fractions. The best means of measuring these would be by a
study of the changes in the nitrogen, such as have been done frequently
in studies of autolysis. As the nitrogen, however, has not been con¬
sidered in these analyses, a comparison of the extractive or water soluble

phosphorus will serve the purpoee: —

Time of collecting after

Water soluble

Lipoid and

death.

extractive P.

Protein P.

1 hour

26*9

. 730

4 hours

24-7

. 75-2

17 hours

24-7

. 75-3

19 hours

23-2

. 767

30 hours (cold chamber)

251

. 75*0

The results, if anything.

show a change

contrary to what might be

expected if autolysis w'ere

proceeding, and.

in view of the fact that

these analyses were made on different samples, the variations are of
little significance. The results are in harmony with other observations
which indicate a very slow rate of autolysis in the brain. Nevertheless,
the material should be collected within 24 hours after death if possible.

Method of Extraction—Outline of Method.

In the plan previously outlined (p. 181) for the separation of the dif¬
ferent groups of constituents the following fractions are first obtained ; —

1 and 2. Fraction soluble in alcohol (85-95 per cent.).

3. Fraction insoluble in alcohol, soluble in hot water.

4. Fraction insoluble in alcohol and hot water.

186

ARCHIVES

Although ether is used in the extraction following the first alcohol, it
does not remove any considerable amount of material and need not be
considered in the above scheme. The apparatus used for the extractions
is a modification of the old form of Wiley extraction apparatus, and was
designed for us, according to our suggestions, by Gallenkamp and Co.,
London. The advantage of this form over the Soxhlet, especially for
work with nerve tissues, consists in the fact that the extraction takes
place at the boiling point of the solvent.

The apparatus (Fig. 1) consists of a wide mouth COj flask of 300 c.c.
capacity into which it is fitted, by means of a ground glass connection, a
small double surface condenser. On the lower end of the condenser are

fused two glass hooks, from which is suspended in a thin platinum wire
sling a 40 c.c. perforated cup. Each condenser is fitted with at least
three interchangeable flasks. If dry heat is used for the extraction
(cf. Electric Plate, Plate I.) the above form of condenser answers admir¬
ably, but should a water batii be used, the escaping steam will condense
on the external surface of the condenser and, creeping into the ground
glass connection, will possibly cause it to stick. With a water bath, a
Hopkin’s condenser (Fig. II.)—-in which the cooling is accomplished from
the inside—prevents this source of annoyance. Electric hot plates have
the disadvantage that they are heated irregularly, but we have found

PLATH I.

I'nrc p. IW).

CHEMICAL EXAMINATION OF BRAIN

187

them, used carefidly, to effect a great saving in time, and also to eliminate
all risk of fire. Plate I. shows a number of extractions proceeding at the
same time; these, when once started, require but little supervision, and
can be left running during the night for the final extractions.

For the extraction the material is transferred to the perforated cups
and first extracted for d-4 hours with 95 per cent, alcohol. As
this removes about nine-tenths of the alcohol soluble portion, it is better
to discontinue heating on account of the danger of decomposing some of
the compounds now in the alcohol solution. The alcohol extraction is

Fig. II.

followed wdtli an ether extraction, and this, although it does not remove
much material, has the adv:intage of rendering the nerve tissue extremely
brittle, so that it can be finely powdered, w hich procedure greatly aids the
completeness of the later extraction. After powdering, the material is
mixed with water and heated; absolute alcohol is then added to bring the
concentration to at least 85 per cent. This procedure ensures the more
complete extraction of those extractives, which are only slowly soluble
in 95 per cent, alcohol, but which, if the extraction were continued long
enough, would finally come out and really belong to the alcohol soluble

188 AJRCHIVES

fraction. The material is again transferred to the cups and extracted for
twelve hours with 95 per cent, alcohol. To continue the extractions
longer than this is hardly necessary, for, although it is practically
impossible to separate completely the constituents of any tissue by
extraction with solvents, the following control experiment indicates that
the error is not very great.

One hundred grammes of brain material were extracted twice with
alcohol and once with ether, as outlined above and described in detail
later, and the amounts of sulphur and phosphorus removed estimated.
The material was then again ground up and remixed and subjected to
another alcohol extraction for twelve hours, and the total sulphur and
phosphorus in the extract estimated. The results are as follows: —

4 hours alcohol, 2 hours ether, 12 hours alcohol extrac¬
tions yielded ... .. . . ... ... ... 2537 mg. BaS 04

A further 12 hours alcohol extraction yielded .. ... 8*5 mg.

280*2

Percentage extracted in first series ... ... ... 97*5

On the same sample phosphorus estimations were made and yielded : —

First fractions . ... . ... 893*1 mg. Mg, P,0,

Final fraction ... ... ... ... ... 8*0 „ „

899*1

Percentage extracted in first series ... ... ... 99*3

Although the total amount of sulphur extracted in the final fraction is
only 0*9 mg. as compared with 1*7 mg. phosphorus, it calculates to a little
higher in percentage of total on account of the smaller amount of total
sulpliur extracted witli alcohol. The completeness of the extraction is,
therefore, fairly satisfactory, especially as the error largely becomes
eliminated in a series of comparative experiments such as we are dealing
with here.

The residue insoluble in alcohol represents essentially proteins (the
amount of glycogen in nerve tissue is too small to be considered) plus a
correction for water soluble alcohol insoluble extractives (about 2 per cent,
of the total residue). As these extractives, however, are rich in inorganic
phosphates and sulphates, it is necessary, after weighing, to extract this
residue with hot water. Eight extractions are usually sufficient. In
these extractions it is well to exercise great care to avoid the danger of
bacterial decomposition, as the results can be completely vitiated by this
source of error.

CHEMICAL EXAMINATION OF BEAIN

m

Details of Method.

One hundred grammes of brain material which have been preserved
in 400 c.c. of absolute alcohol and kept with occasional heating to ensure
complete coagulation of the proteins for not less than two or more than
four months, are transferred to the cups as follows:—The perforations of
three cups are covered with filter paper by cutting one round piece to fit
the bottom end and one oblong piece to fold against the side. The filter
paper is moistened with alcohol and pressed firmly against the sides with
a glass rod. Even if all the perforations are covered with filter paper,
small particles of brain material w ill pass through the cracks where the
two pieces join, but if the adjustment of the filter |)aper has been care¬
fully done, these •cracks soon fill up and the filtrate is perfectly clear.
The cups are then placed in large funnels which drain into beakers
placed below and the brain material carefully transferred. It requires
three cups to hold 100 grammes of brain material.

At first, as stated above, the filtrate is not clear, but when it begins
to come through clear the beakers are changed and the first filtrate
refiltered. After all the material has been transferred to the cups in this
manner and the last particles washed in with hot alcohol, the cups are
allowed to drain and then carefully transferred to the extraction
apparatus.

In order to ensure a better distribution of the alcohol, as it drips into
the cup from the condenser, a perforated plate is placed on top of the
brain material in the cup; the extraction is started with 95 per cent,
alcohol at the medium temperature of the electric plate and continued
for 3-4 hours. With this temperature the alcohol boils, and about every
tw^o seconds one drop falls from the condenser and thus keeps the material
thoroughly soaked. After 3-4 hours the apparatus is allow’ed to cool,
clean fiasks substituted, and an ether extraction continued for 2-3 hours.
The apparatus is again allowed to cool and the material carefully ground
up to as fine a powder as possible in an agate mortar. When removing
the material from the cups, care must be taken not to disturb the filter
paper, as it is to be used again when the material is returned to the cups.
The powdering of the material may be a slow and laborious process, but
should be carefully and completely done in order to ensure complete
extraction later. The pow^dered material is transferred to a 600 c.c. Jena
flask, moistened with 50 c.c. water and heated on a water bath for one
hour. At the end of this time 450 c.c. absolute alcohol are added; the
mixture is warmed, well shaken and allowed to stand over-night. The
material is again filtered into the cups, as previously described, and
extracted for twelve hours with 95 per cent, alcohol. The flasks contain-

11)0

AECHJVES

iiig the alcoholic extracts, the beakers containing the filtrates, and the
flasks containing the ether extract are put aside, and their manipulation
will be described later under the separation of the lipoids. The residue in
the cups is now transferred to a weighed beaker or platinum basin and
dried at 105°-110° C. to constant weight. This weight represents the total
protein plus about 2 per cent, of extractives and ash (not removed by the
alcohol), and is designated as fraction 3 and 4. It is now necessary to
take an aliquot part for the estimation. In the dry and very

hygioscopic condition of the protein residue this is practically impossible;
therefore, after weighing, it is allowed to stand over-night in order to
come back into equilibrium w ith tlie moisture of the air, it is then again
weighed and an aliquot part of one gramme taken for the 85,44 estima¬
tion (p. 196). The remainder is transferred to a 300 c.c. Jena flask
and moistened with 100 c.c. water; the flask is plugged with a loose
cotton wool stopper and heated on a water bath for one hour. This
eliminates all risk of bacterial decomposition until next day, when the
fluid is filtered into a 600 c.c. Jena beaker. The residue is washed back
into the flask and 100 c.c. w ater again added and the process repeated on
each of eight successive days. It is imperative that after the cotton wool
stopper has been removed, the material is not kept too long before it is
again sterilised. The precautions are merely those w^hich will occur to
anyone familiar with bacteriological technique. One point, however,
may escape notice. In case it is not possible on account of press of work
to start the w'ater extractions the next day after the residue has been
dried, it is not safe to allow it to stand. The amount of moisture which
is absorbed from the air is sufficient to enable bacteriological growth to
commence, and we have frequently noticed samples which, although
they w'ere dry w hen transferred to a dry flask, develop a decided odour of
putrefaction on standing. It is advisable in such a case to thoroughly
soak the residue in 15-20 c.c. chloroform and carefully stopper it before
putting it aside.

The filtrates from the hot-water extractions, as they stand for more
than a week before the process is ended, are also liable to bacterial decom¬
position. The addition of 5 c.c. of cone, hydrochloric acid to the first
filtrate avoids this difficulty. When the filtrates accumulate to
more than 400 c.c., they must be evaporated so as to keep the
bulk at about 300 c.c. Tlie precipitate at first formed when the acid is
added to the first filtrate is practically redissolved by this process. A
slierht amount of a browmish precipitate sometimes forms in the solution,
and should be filtered out before the SJ estimation is made, but not
before the total S 3 estimation, as it may contain traces of organic sulphur
compounds. Tlie united filtrates, which should not exceed 300 c.c. in

CHEMICAL EXAMINATION OF BHAIN

191

bulk, are then used for the SJ or S.j and P, estimations ( pp. 196 & 200). The
residue insoluble in hot water is burned by Neumann’s method with
nitric and sulphuric acids, and used for the determination (p. 200).

Separation of Lipoids.

The alcohol soluble portion (fraction 1 and 2 of the 100 gramme of
brain matter) is now contained in three flasks from the first alcohol
extraction, three flasks from the ether extraction, two flasks from the
second alcohol extraction, and five beakers, three from the first filtrate in
which the sample was originally preserved, and two from the treatment
after grinding the material in agate mortar. In the first set of these
flasks a considerable amount has separated on cooling. The supernatant
liquid is carefully decanted off into several 250 c.c. Jena glass evaporating
dishes, into which all the other extracts are poured as the evaporation
proceeds. The evaporation must be carried on at a low temperature, and
in no case must the samples be evaporated to dryness. After they have
been reduced to small volume, the residual liquids are allowed to cool and
the evaporation finished in a vacuum desiccator. All the alcohol must be
removed as completely as possible, as it interferes with the later pro¬
cedure. After about one week the samples are dry and free from alcohol.
They are then moistened with water, allowed to stand over night and
the next day transferred to a graduated 1,000 c.c. flask. If the material
has been well moistened it can easily be removed from the beakers and
extraction flasks as a watery emulsion. After all has been transferred
to the litre flask it is well shaken and 10 c.c. cone, hydrochloric acid
added. After again shaking 15 c.c. chloroform are added and the bulk
made up to 1,000 c.c., well shaken and allowed to stand in a cool place
for three to seven days, when a perfectly clear filtrate can be obtained.
The danger of decomposition of the lipoids from this acid treatment has
already been investigated (1) and occasional control experiments made in
the course of the work have confirmed these negative results. If the
filtrate is not perfectly clear, it can be shaken up again with chloroform
and allowed to stand in a cool place; the solution is then again filtered
through a fresh filter paper. In order to obtain a complete separation of
the lipoids and the water soluble extractives it would be necessary to wash
the lipoid precipitate with acid water. This, however, has not been found
practicable, but instead the filter paper containing the lipoid precipi¬
tate is allowed to drain thoroughly and the volume of the filtrate
recorded. The difference between this volume and the total volume
minus the chloroform approximately represents the amount of liquid
adhering to the lipoid precipitate. In order to make this figure more

192

A&CHITES

accurate it is necessary to start the filtration through a dry filter paper.
The following example will illustrate the case (compare also similar case,
p. 197):-

The residue from the evaporation of the total alcoholic extracts of
100 gms. of brain matter were emulsified with water and 10 c.c. HCl and
15 c.c. CHCI 3 added. The whole was made up to 1,000 c.c., well shaken
and allowed to stand five days. The filtrate measured 780 c.c., and
yielded on evaporation by the method of sulphur estimation (p. 195)
69*7 mg. BaSO^. The lipoid precipitate collected from the filter paper
by dissolving in hot alcohol yielded 259*0 mg. BaSO^. Considering that
if all the filtrate adhering to the lipoids could have been recovered and
allowing for the volume of chloroform, the part of the 205 c.c. difference
must be due to the bulk of the lipoids, but if we consider that 100
grammes of brain matter contains only 22 grammes of solids, of which
60 per cent., or 13 giammes, is represented by lipoids, the error is not
very considerable. Therefore, we have assumed that the 205 c.c. have the
same composition as the other 780 c.c., and that, by calculation, they
would yield 18*3 rag. BaSO^, which must be subtracted from the lipoid
sulphur, leaving 240*7 rag. BaSO^, total S^, and added to the extractive
sulphur, making 88*0 rag. BaSO^—total S^. The proportional error in
this manner of correction is probably much less than would be incurred
by attempting to wash the lipoids.

EsTlM.VTlON OF vSuLPHUR.

Outline of method : —

In searching for a method suitable for the estimation of sulphur in
the moist fatty material with which we are dealing, and in which it is
sometimes necessary to estimate accurately 5-10 mg. of sulphur in
2-3 grammes of organic material, the following difficulties must be taken
into account:— [a) The possibility of Joss from too rapid combustion,
especially with dry material, and the danger of spattering with material
in a semi-liquid state, (b) The risk of incomplete combustion or oxida¬
tion, dxie to caking of the fusion mixture.

In an excellent review of all the methods Folin (29) finally recommends
the sodium peroxide method. This, however, did not prove satisfactory
with the moist fatty material we have been investigating, and the method
used by Schmiedeberg in his laboratory has been adopted. This
method gives very good results in cases where large amounts of
organic material have to be destroyed, but it requires much time and
care. The principle of the method consists in the gradual charring
with an alcohol burner of the material in a mixture of seven

CllKMlCAL EXAMIiNATIOjS OF 13KA1X

193

parts sodium carbonate and one part potassium nitrate. This proportion
of potassium and sodium avoids the source of error, poin ted out by Folin,
in the precipitation of the barium sulphate. The final burning is made
with a Barthel alcohol burner at a temperature just below the fusion
point of the mixture. After acidifying with hydrochloric acid a few
drops of bromine water are added to remove any nitrous oxide in the
solution, and the precipitation is done in the usual way.

Description of nuthod —(a) Method of fusion ,—One gramme of the
material is mixed with at least 12-15 grammes of the fusion mixture
(Xa^COg seven parts, KXO, one part) in,a lipped silver crucible of 30 c.c.
capacity, and very yradiudly charred over an alcohol spirit lamp. This
process should take several hours, and the fumes from the burning should
never rise so rapidly as to discolour very much the top layer of the fusion
mixture. Should the fumes come off too rapidly, the spirit lamp must be
removed for a short time and fresh fusion mixture sprinkled on the top
of the mixture. In this manner the fumes arising from the burning are
made to pass through a layer of fresh fusion mixture, and any sulphur
fumes are kept back. After the material has completely charred and no
more fumes come off even on placing the flame in direct contact with the
crucible, the mass after cooling is thoroughly powdered in an agate
mortar with the addition of about 1-2 grammes of fresh fusion mixture.
It is then returned to the crucible, a layer of fusion mixture sprinkled
on top, and heated with the Barthel alcohol burner at a temperature
sufficiently low to avoid caking of the fusion mixture. The burning must
not be hurried. The combustion will be more complete after heating at
a moderately low- temperature for half an hour, than by trying to force
the process, for any caking is apt to include black specks which are
difficult to oxidise, and not only may contain unoxidised sulphur, but
also actually reduce some of the sulphates already formed, e.g.^ the
Leblanc soda ash process. The fusion mixture, after cooling, is trans¬
ferred to a 600 c.c. Jena Erlenmeyer flask, and the crucible boiled out
twice with hot w^ater to dissolve any silver sulphate which may have
formed through contact with the crucible. If the mixture has caked a
little this process of boiling out becomes much more difficult, and almost
invariably a black stain of silver sulphide will be seen on the crucible.
The loss from this source of error may amount to 1 mg. of BaSO^. The
solution with washings is carefully acidified with hydrochloric acid and
heated on a water bath to drive off the COj evolved. It is then filtered
and to the boiling filtrate 5-10 c.c. of 10 per cent. BaClg solution are
added and the barium sulphate estimated in the usual manner.

It is usually considered advisable in making sulphate estimations to
obtain a weighing of 100 mg. or more of barium sulphate. As this would

m

AJLCilXYES

involve the destruction oi very large amounts oi organic material it was
decided in these analyses to aim at 40-60 mg. of barium sulphate, con¬
sidering that the error occasiojied by a somewhat smaller weighing would
be more than compensated for by the more complete extraction of the
material and the decrease in the sources of error accompanying the
destruction of large amounts of organic material. The 100 grammes
sample of moist brain material recommended in the collection of material
accomplishes this.

Estimation of S^.- The lipoids after filtration following the acid
chloroform precipitation, represent a sticky mass adhering to the flask and
filter paper. The mass on the filter paper can be washed off with hot
alcohol. The destruction of all the lipoids from a 100-gramme sample,
however, involves an almost hopeless task, and would yield about 250 mg.
barium sulphate. In order to keep the estimation within the limits of
accuracy, adopted for the other fiactions, it becomes necessary, therefore,
to take an aliquot part. This can only be done by dissolving the mass in
alcohol in the 1,000 c.c. flask in which the preiupitation was originally
made and making up to the 1,000 c.c. mark with alcohol; 200 c.c. of this
solution should then be used. This procedure, however, is complicated
by the fact that the lipoids are only soluble in hot alcohol, which makes
the taking of an aliquot part a matter of some difficulty. Before finally
adopting this method, therefore, it was necessary to try some control
experiments. Tbe.se were done as follows : —

Control Exp. 1 .—A 50-gram me sample of brain w^as treated in the
usual way, and the lipoids, after dissolvijig in hot alcohol, made up to
500 c.c. While warm 200 c.c. w^ere taken with a warm pipette and the
sulphur estimated. The sulphur in tlie rejiiaining 300 c.c. of the solu¬
tion was then also estimated. The yields w^ere 24’0 mg. and 36'0 mg.
BaSO^ respectively, whicli figures are in the proportion of 200:300.

Coixirol Exp. 11 .—From three lOO-gramme samples of three brains the
lipoids were made up to 1,000 c.c. and 200 c.c. aliquot parts taken. From
these same brains 20-gramme samples of material were collected, and the
sulphur in the total lipoids estimated without taking an aliquot part.
The following table gives the results : —

Cask No.

]0

*28

1*2

S. CATAJDLATED IN PER CENT. OF

Barium Sulphate. dry matter.

.\liquot part, ‘2i» gnn. Bample. Aliquot part. 20 grm.

•M*8 . mg. 0*154 . 0*135

•^)3*4 mg. . 31*6 mg. 0*10*2 . 0*007

43*5 mg. . 42 0 mg. 0*1*25 . 0*121

The agreement is better in the last two samples which were estimated
at a later time w hen more experience had been acquired in taking the
aliquot part. There is a tendency for the aliquot part to come out

CHKM1(J.AJL KXAMixNATlUiS Ol BKAiiN

195

liiglier; this can no doubt be accounted for by the cooling of the liquid
in the pipetto, and must be avoided as much as possible.

Control Exp. III. —Seventy-seven grammes of blood which should
contain no lipoid sulphur were treated in the same way. All the lipoid
precipitate was destroyed and gave no weighable quantity of barium
sulphate. Water soluble organic and inorganic sulphates do not, there¬
fore, adhere to the lipoid precipitate in sufficient amount to account
for the quantities found. This experiment serves as a negative control.

Details of method .—After the lipoid precipitate has been allowed to
drain and the volume of the filtrate recorded, the funnel is placed in the
litre flask originally used and a hole punched in the bottom of the filter
paper witli a glass rod. By means of a hot alcohol wash bottle all the
sticky mass adhering to the filter paper and to the glass rod is completely
washed into the flask. It is better to use 95 per cent, alcohol for this.
The amount of alcohol in the flask should now be 400-600 c.c.; the bulk
is made up to about 900 c.c. with absolute alcohol and the whole warmed
on a water bath until complete solution lias taken place. Great care
must be taken that the sticky mass, which has a tendency to adhere to
the bottom of the Hask and which may easily be missed as it is rather
transparent, has been completely dissolved. The shaking of the flask
must also be carefully done, as too violent shaking may cause the liquid to
boil over and thus spoil the analysis. When everything appears to have
dissolved, enough warm alcohol is added to make the bulk 1,000 c.c.
While keeping the flask on the water bath, a 100 c.c. pipette is now
introduced, and by carefulh" drawing up the liquid and allowing it to
again flow back into the flask, at the same time turning the flask, a
uniform mixture can be obtained. This treatment at the same time
warms the pipette. 200 c.c. are removed as carefully and rapidly as
l) 08 sible, evaporated to a semi-pasty condition and then mixed with fusion
mixture.

It is perfectly futile to attempt the destruction of this organic matter
with less than 40 grammes of fusion mixture distributed between three
silver crucibles of the size previously described. The difficulties
experienced at this point will soon convince anyone how practically
impossible it would be to try to burn all the lipoid precipitate in this
manner instead of taking an aliquot part. There seems to be an unneces¬
sary amount of detail in this description, but we feel convinced that
anyone attempting to repeat these analyses with any aim at accuracy
would wisli there had been more, as tlie factors which from time to time
tended to spoil analyses seemed almost infinite.

Estimation of S^. -The water solution filtered from the lipoid precipi¬
tate is evaporated to moist dryness, mixed with 10 grammes fusion

N 2

196

ARCHIVES

mixture and the sulphur estimated. In adding the fusion mixture care
must be taken to prevent excessive spattering due to the liberation of COj
by the acid present. It is also well not to heat this estimation to as high
a temj)erature with the Barthel burner as the others, on account of the
fact that the larger amount of sodium chloride present is liable to cause it
to cake, also the sodium chloride is liable to attack the silver crucibles
and bring about the formation of a colloidal form of silver chloride in the
final solution, and this spoils the neatness of the barium sulphate
precipitation. It might also be advisable to use a platinum crucible for
this estimation.

J^sliination of SJ.—The filtrate from a second 100 -gramme sample is
evaporated to about 300 c.c., filtered, if necessary, and the sulphates
estimated directly by barium chloride. The weighings of barium sulphate
liere ainount to about 15 mg. Too much confidence must therefore
not be placed in this result; it is better to regard it in the nature of a
correction, by means of which it is po.ssible to estimate the organic part
of the Sj fraction. Sulphates appear to be eliminated from the tissues as
rapidly as they are formed, so that the amount present at any time is
never very great and the variations are of comparatively little
significance (3-4 per cent, of total S).

Eslinuitioa of and S^. — The protein residue insoluble in alcohol is
dried, weighed, and allowed to come into equilibrium with the moisture of
the air as previously described. One gramme is then taken, mixed with
12 grammes fusion mixture and tlie sulphur estimated. Great care must
be taken not to liurry the preliminary burning, as sulphur may be lost on
accoimt of the dry nature of the material. The result represents 83 ^. 4 .
The remainder of the protein residue is then extracted with hot water
(p. 190), the extracts evaporated and mixed with 10 grammes fusion
mixture. This result represents the S^, and subtracted from the S 3+4
gives the or protein fraction.

Estimation of From another 100-gramrae sample the eight hot-
water extracts of the alcohol insoluble residue are evaporated with 5 c.c.
cone. HCl to 300 c.c., filtered if necessary, and the sulphates estimated
directly with barium chloride. It is a question whether 83^.4 minus Sj or
S.J 4 4 minus S 3 more accurately represents the protein sulphur. The
portion of S, of organic nature usually amounts to about 5 per cent, of
the total sulphur, and is mainly precipitated by phosphotungstic acid.
The amounts, however, are so small that their investigation will be a
matter of some difficulty; in recording the analyses in this paper, there¬
fore, the latter figure minus SJ is invariably referred to as the

protein or rather protein-like sulphur.

Method of keejnnff analytiral records and ((dcidation of results .— The

CHEMICAL EXAMINATION OF IIRAIN

1!)7

method of notation here used has already been explained, and it seemed
of interest to dcvscribe in a little more detail not only the method of
calculating the results but also a method of keeping laboratory notes on
the card catalogue system, which may be of general value in investiga¬
tions of this kind. The copy of a card from one of the cases with
analytical results and calculation in logarithms follows:—•

(’ask /O. C. K. S. Age 4:{. Dept, of Path. Material collected 5.1.08. Uiiiv. ot

Chicago. Analysis begun 8.1.08.

100 g. 10 HCl, 15 CHCI3, 2 dajs filt.

81 gave 014’lx5) mg. BaSO.t

S, „ (.58-lx^) mg.BaSO*

Protein residue weighed 0*671 air dry
83-1-4 1*000 g. air dry gave 5;j-3 uig. BaSO,

85 8*671 g. „ „ 44*0 „

11)0 K. 10 HCl, 15 CHC1.„ 5 days filt.
OH')

S.‘ gave 12 0 X ^^Tiig.BaSO,
sj gave 1*2*5 mg. BaSO 4

o o

s.

!)12fi

7642

7267

6435

0769

0969

1908

8513

1377

1:177

8808

1:177

1032

0120

9854

9854

1961

2346

3177

1377

8408

7666

1377

04*25

1377

00:14

0425

9:181

9934

1021

4554

0440

807:1

8285

:1272

04*25

0425

04*25

0425

41*20

0015

7860

*2847

S.

s'

:5-<)' -

10%

64*2

«-l9i

1 •ojr

1 ’• r

o

Explanation of card ,—The first 100 gramme sample was extracted and
the alcohol residue after emulsifying precipitated with 10 c.c. HCl and
15 c.c. CHCI 3 and made up to 1,000 c.c. After standing for two days,
filtered, and the volume of filtrate 830 c.c. recorded, 710 c.c. of this
filtrate were evaporated and gave 58*1 mg. BaSO^. The aliquot part of
the lipoids (200 c.c. of 1,000 c.c.) gave 44*1 mg. BaSO,. The calculation
is as follows: —

log 7>8*1

. 7642

log 710

8513

Sjj in 1 c c.

. 9129

log BaSO 4 to 8

. 1377

log 985 (total filtrate)

. 00;14

0+40

log for total S

. 0+27

82 in of total 8 ...

. 0013

Anti log.

. 10 ' 0 “..n

log 53*3.

7*267

log BaSO^ to 8 ..

. 1377

log 9*671

. 9854

8498

log for total S ...

. 0427

log S 3 4 .1

. 8071

Anti log ...

.. 64*2^0

log for 85 ini c.c ... . ... 1 U 21 ^

log 155 (filtrate clinging to li|)oi(ls). 1003

Correction for S, ■. ... 1032

Antilog for correction 12*7 ing.

(44*1 X 5) -12*7 = *207*8 ing.

log *207*8 (actual 8 after coit.) :n77

log BaS ()4 to S ... ... ... 1377

4554

log for total 8 ... 0427

Si in of total 8 .. ... .. 4127

Antilog . .. ... 25*0

Calculation of total 8 .

Antilog 04*10 . . 1107

45A1 . 2852

„ 8408 . 7076

log 11035 (total S) is 0427.

11035

1!J8

ARCHIVES

Till' oilier caleulutions follow ou the principles here outlined, and should
he easily understood. SJ and were done on second luO-gmmme
sample. It will be evident that by thus expressing the results in per
cent, of total sulphur the water estimation does not need to be taken into
account. In several cases the total S in per cent, of dry tissue was esti¬
mated directly on a sample of brain matter and found to check that
obtained by calculation from the different fractions. The phosphorus
estimations were recorded in similar ways on cards of a different colour,
and were calculated in practically the same way as here described.

EsTiM.vnoN OF Phosphorus.

Outline itf method .—^In order not to multiply needlessly the work,
a method of estimating phosphorus was adopted which could be applied
to the same material used for the sulphur estimations. For this purpose
the filtrate from the BaSO^ precipitate, which should contain all the
phosphorus as phosphoric acid, was treated with ferric chloride and
ammonia. In order to test if this method removed all the phosphorus as
iron phosphate, controls w'ere made with the filtrates, and these indicated
ihat the precipitation has to be repeated in order to ensure complete
removal. The following results wdll illustrate this:—-

('ase.
4-J \\

First Fe ppt.

14:;-4
5»4'H „

Socoiid Fe |)|)t.
contained
H I niju:. Fgt);

V.VH ..

The use of a greater amount of iron in the first place doe:s not obviate
this diffii'ulty. Another source of error in this method lies in the fact
that on account of the large amount of iron used, the magnesium pyro¬
phosphate preci])itates are very apt to show* a slight iron stain. No
amount of washing or control of the amount of iron can obviate this, as
the iron seems to enter into the complex molecule of the ammonium
phosphomolybdate as a component part. However, the following results
indicate that the error is not great and is well within the variations of
(lie inaterial : —

ise.

Fi‘

Fei-ceiitajj^c error.

mg.

mg.

in

p,

021 .

F4

F4

:io

1*.

141-J .

1-0

70

F.,

inn-H

Fo

•jn

F.

‘J077

10

t) o

7o

I’i

‘»7-|

0'.‘>

FO

Tli^

e iron

was estimated

coloiimetrically

with KCNS In¬

comparison with

<H1

iron sohition of kuov

rn strength. It

is not necessary

to enter into the

CllKMICAL EXAMINATION OF BRAIN

199

details of this method here as the usual errors would not very seriously
ahect the above observations.

Details of method ,—To filtrate from BaSO^ precipitation add from
1-3 c.e. of a 20 per cent, ferric chloride solution. Add 5-10 c.c.
ammonia, sufficient to make an excess, boil until the fumes of ammonia
are no longer given off and then filter. To the filtrate add again 1 c.c.
ferric chloride solution and repeat precipitation. Place the funnel con¬
taining the tAvo precipitates in the flask in which the precipitation has
been made, punch a hole in the bottom of the filter paper with a glass
rod, and wash the precipitate into the flask wdth hot water. The filter
paper is then moistened with 1 c.c. nitric acid and w^ashed until all traces
of iron are removed. Another cubic centimetre of nitric acid is usually
sufficient to dissolve the whole precipitate. It is necessary to effect this
transference while the precipitate is quite moist, as it becomes hard and
insoluble in nitric acid on standing. In the and Pj estimations it is
desirable at this point to filter tlie solution and to take an aliquot part
150 of 250 c.c,), for the amount of phosphorus in these fractions is
comparatively large, and the precipitates obtained are too bulky to
manipulate neatly; also good re-agents may be w asted unnecessarily.

In this solution the phosphorus is estimated in the usual way (30) with
nitro-molybdate solution in the presence of an excess* of ammonium
nitrate. All estimations recorded in this communication were finally
weighed as MgjPjO^.

Estimation of P,.—This fraction is estimated in the filtrate from the

precipitation, and a correction applied for P^ in the same manner as
in the calculation. The method devised by Koch and Woods (30) for
the separation of lecithin and kephalin has been found to vary so much
with the conditions of the experiment that the results seem hardly
reliable.

Estimation of —This estimation is made on the filtrate of the Sg
barium sulphate precipitation. With regrard to the esfimation of PJ
the results have been uncertain. Grindley f31) has attempted the
separate estimation of inorganic and organic combined phosphates, but
it does not appear to us at all certain that his method may not break
up organic radicles. One experiment was made to estimate the phos¬
phates directly in this fraction with magnesia mixture. The results are

as follows: —

BY FUSION IN PER DIRECT BY MAGNESIA

CENT. OF TOTAL P. ‘ MIXTURE.

Case 26 . 11*4 5'2

There does appear to be present a considerable amount of organically
combined phosphates which are not broken up by this method.

200

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Estimution of Pg.—This fraction seems to consist entirely of PJ
inorganic phosphates, unless we are here again dealing with the breaking
up of organic radicles: —

P. BY DIBRCT PPTN WITH

PHOSPHORUS BY Kl'SloN. NITRO-MOLTBDaTK

Case 2(> ... . ... P H . P‘P

Case 70 , .. ... 10*0 . 10'.5

In recording the results Pg and P 3 are added together under the term
extractive phosphorus.

Estimation of P^.—The residue after extraction with hot water is
burned by Neumann’s metliod and the phosphorus estimated in the usual
way. The very great variations observed in the results obtained by this
method, still further emphasise the difficulties of estimating milli¬
grammes of phosphorus in grammes of organic material.

Estimation of Water.

The amount of blood in the tissues at death and the accidental and
almost uncontrollable variations in the amount of drying during the
collection of the material are apt to introduce differences in the water
content of various brains, and for these reasons not much importance
has been attached to the comparatively slight variations which occur with
some normal and pathological brains. It is, however, necessary to esti¬
mate the water content in an investigation of this kind in order to deter¬
mine the various constituents in percentage of the total solids.

It has been already demonstrated ( 1 ) that it is difficult to dry to
constant weight material of colloidal nature, and that the best method
consists in drjdng in vacuo below the coagulation point of the colloid.
This method has been adopted. Weighed quantities of minced brain
matter have been spread out on one of two tared (paired) watch glasses
fitted with a clip, allowed to remain in a vacuum desiccator for some time
and then dried to constant weight in a vacuum oven at 40^-42^ C. When
constant weight is attained, it is found that raising the temperature to
100 ® C. does not materially affect the result.

Benedikt (32) has since devi.sed a method which in principle resembles
our method, but offers no special advantages.

The amount of material taken should be as near as possible
2 grammes; a larger quantity than this makes the drying a very long
and tedious operation, while smaller amounts on account of their small¬
ness may introduce error. A number of moisture determinations made
in duplicate are given below, and the results not only show a fair check
of accuracy of the method, but also indicate that the mincing process
gives a uniform mixture of the grey and white matter, as the samples

CHEMICAL EXAMINATION OF BRAIN

201

were taken in each instance from quite distinct portions of the minced
material; —

No. f)F CASK.

UK

41.

2M.

42.

Per cent, of moi.stiire

( («0

1 (!>)

X X

77-41

77-oO

78-:{8

78-:m

77-0-2

77-49

7(5-08

7(>-8!;

lOsTIMATION OF (iROl TS OF CoNSTITl ENTS.

rroltinsy extractives and ash. —The method is essentially that outlined
before (1). The proteins are calculateil by subtracting the weight of
the residue from the hot-water extractions from the original dry weight
of the alcohol insoluble residue. The extractives are made up from the
above water soluble residue and the residue from the filtrate derived
from the lipoid precipitation corrected for total volume. The ash is the
residue obtained on incineration of the extractives at dull red heat. Not
many observations are recorded in these pages, as tiiey did not appear
to sliow any great variations.

Cerehrins .—This estimation is accomplished by determining gravi-
metrically with Fehling’s solution the amount of galactose split oil with
dilute HCl.

When the aliquot part of the lipoid precipitate of 100 grammes brain
matter is being taken for the estimation another 100 c.c. (i.e., one-tenth
aliquot part) is taken for the cerebrin estimation. This is placed in a
litre flask and the alcohol and chloroform completely evaporated. Even
then, it is well to add a little distilled w^ater and to boil for some time, for
the presence of alcohol and chloroform is liable to give rise to other
reducing compounds, e.g., phosgene, and thus vitiate the result. A large
riask is necessary, for the frothing is rather considerable, and unless this
precaution is heeded will cause much annoyance. The bulk of the
solution is made up to 100 c.c. and c.c. HCl added. The flask is then
fitted with a reflux condenser, placed on a sand bath and gently heated
for at least 24 hours, not necessarily consecutive. Towards the end of
the hydrolysis the solution may appear milky; it is advisable then to add
a few^ more drops of cone. HCl, when this will disappear. The solution
with w’ashings is now transferred to a 250 c.c. graduated flask; sodium
sulphate, solid or in concentrated solution, is added until all precipitation
is complete and the supernatant fluid is clear and bright, then the bulk
is made up to 250 c.c., the flask well shaken, and allowed to stand for a
while. The solution is then filtered and an aliquot part 100-150 c.c.
taken ; to this, after carefully neutralising, is added 100 c.c. freshly-made
Fehling’s solution, and the whole stirred and placed on a water bath for
four hours. At the end of that time the precipitate is collected on a
Gooch asbestos filter, washed with hot distilled water, ignited and

2m

ARCHIVES

weighed as CuO, or reduced further and weighed as metallic copper.
From this weighing the equivalent amount of galactose is ascertained, and
an approximation of the amount of cerebrin obtained by multiplication
with 10()/21'8, Thierfelder s factor for the sugar equivalent of cerebrin.
The Fehliug’s solution must always be in considerable excess, and dur¬
ing the precipitation the solution should not be allowed to evaporate to
any great extent.

Sugar determinations have been made on the filtrates obtained from
the lipoid precipitation. In each instance, after boiling oft the chloro¬
form present, no reduction occurred.

Cholesterin. —Tlie method of Hitter (83) was again used in the few
fholesterin determinations made in this work.

III. Analytical Hesults.

The above methods permit the comparison of normal and pathological
material from three points of view: —

1. Condition of mUrition of tissue .—This considers the variations in the
three principal food constituents; proteins, fats (lipoids) and carbo¬
hydrates (cerebrin).

2. Changes in oxidations. —It will be very difficult to draw any con¬
clusions with regard to the intensity of oxidations from any variations
in the sulphates. It appears that the sulphates, like carbon dioxide and
urea, are very rapidly eliminated from the tissues and soon appear in the
urine. As a result they are only found in the tissues in amounts too small
to permit any conclusions based on variations (15 mg. SO^ in 100 grammes
brain material). To attempt to study the oxidations by the difference in
compo.sition of the blood going to and coming from the brain, such as Hill
(34) has attempted with carbon dioxide, would be quite out of the question
with material which cannot be obtained until after death. It remains,
therefore, to compare variations in the intermediary oxidation compound
which appears to have a greater affinity for some constituents of the
protoplasm, and is hence not eliminated so rapidly, i.e., the taurin-like
compound described by one of us (13), here referred to as neutral sulphur.

3. Destructive changes accompanied hy re pa rat ire groivth. —These
changes it is proposed to study by the variations in the phosphorus. An
increase in extractive phosphorus would thus indicate a period of
increased growth, together with a greater supply of material from which
TO build up the more complex phosphoric acid derivatives. This increase
in extractive phosphates may be due to increased food supply, or during
destructive changes to increased breaking down of complex derivatives.

CUEMICAL EXAMl^ATION OF BRAIN

203

It is necessary to bear in mind, in looking over the results of these
methods, that they only express a relative change. Thus if we find that
the total phosphorus of a brain of a general paralytic expressed in per¬
centage of dry matter is the same as that of the normal, it is not correct to
conclude that such a brain has not lost phosphorus as the result of the
destructive changes which we know have taken place. It merely means
that tlie relative proportion has not changed. In expressing the results
for the various groups in the sulphur and phosphorus derivatives, it
seemed better to give them in percentage of total phosphorus and sulphur.
This eliminates a number of errors and permits of* a very good comparison
of the different samples with one another, besides enabling tiie comparison
of these results with analyses made by other investigators. A great many
interesting investigations of pathological material are vitiated by lack of
attention to this point. The system of notation used in the analytical
work and there explained is here translated into terms which are more
familiar: —

Protein tfulphiir represents 8 ^ j minus S'.

Lipoid sulphur represents S^.

Neutral sulphur represents minus SJ.

Inorganic sulphur represents plus SJ.

An explanation may not be out of place for the term neutral sulphur.
It represents a combination of sulphur which does not split off sul¬
phuric acid on prolonged boiling with hydrochloric acid, neither does
it form lead sulphide on boiling with alkali and lead acetate. The term
neutral is used in contradistinction to sulphates or sulphuric acid, and
represents merely a makeshift until the chemical nature of this compound
or group of compounds can be more definitely established.

Phosphorus group: —

Protein phosphorus represents P^.

Lipoid phosphorus represents P^.

Extractive phosphorus represents P 2 plus P 3 .

It seems much better to express the results in this manner than to
attempt to calculate protein phosphorus into nucleo-proteins or lipoid
phosphorus into lecithin, until we know a great deal more of the chemical
nature of these compounds, wdiich at present can only be designated as
rather indefinite groups. In a few tables for better comparison the
lecithin and kephalin w^ere occasionally calculated from the lipoid phos¬
phorus by multiplication with the factor 25‘77.

Tlie word extractive in these investigations is used on the old basis
originally intended by Liebig when he used the term. It has become the
custom of some investigators to refer to lipoid phosphorus as extractive.

204

ARCHIVES

because it is extracted with alcohol. This is incorrect, and only brings
confusion to the term originally used.

Changes with age ,—^We will first consider the variations in the relative
composition of the nervous system at different ages. A preliminary
report of this subject we gave to the Physiological Society (25): —

('OMCARISON OF TIrATNS AT DIFFERENT AgeS.
Table I.

Case 13.

Case 14.

Case 15.

AgCjC weeks ?

Weight,

640 grammes.

Whole brain.

Age, 2 years ?
Weight, 1100 grammes

Age. 19 years
Weight, 1670 grammes.

Cortex. ^

Corpus.

callosum.

Cortex.

Corpus.

callosum.

Proteins

4b()

4^-4

31-9

47.1

27-1

Extractives

12‘0

100

.5*9

9-0

3-9

Ash

m

.V8

3-2

.5-9

2'4

Lecithins and kephalins

242

247

26*3

237

31-0

Cerebrins

&9

8-8

17-2

8-8

18-3

Lipoid S. as SO ^

o-i

o-i

0*5

in

o-r)

('holesterin (by diff.) ..

1-9

2-4

15-0

4-9

lb*8

Total S.

0*52

1

0-53

0-63 1

0-46

0*.50

Total P.

^ 172

lv)0

1-40 !

1-45

1*4,5

Moisture

8878

84*49

76-4r,

83 17

69*87

Diiitrihiftion <>f Snljjhirr in pvr reni. of fotnl S.

i

_

[

Protein 8.

62

63

.5.5

76-5

.56

Lipoid 8,

6

27

7

36

Neutral 8.

26

22

13

10

.5

Inorganic 8.

6

'9

•5

6

3'.5

])inirihifiioo of PJojHpJioriiH in per rrni. of total I\

Protein P.

5

6

6

5

5

Lipoid P.

. 54 I

62

72

63

81

Extractive P.

41

! 1

32

22

32

15

CHEMICAL EXAMLNATIOX OF HttAIN

205

Two additional eases were studied, and are given in the followilig
table compared wdth Case 13 : —

Table 11.

' Cask 13.

Case 10.

Cask 70.

' Agr-, 6 weeks ?

Age 24 years | Age 43 years S

1 Weight,

Weight,

Weight,

1 640 grammefl.

1230 grammes. | 1400 grammes.

W'hole brain.

WMiole brain.

Whole Viram.

Protein 8.

...[ «2

OU

ti2'5

Lipoid 8. ...

.. ti

27

26

Neutral 8.

.. 1 -it)

9-0

8

Inorganic 8.

■i

2 :J-5

Protein P. .

.. :>

4 '

6

Lipoid P.

. 1 rA

78 1 75

Extractive 1*.

41

28

19

In the above tables is to be observed with the growth of the brain: —

1. A decrease in moisture, proteins, extractives, and ash, a change
usually found in growing tissues.

2, An increase in cerebrin, lipoid-sulphur and cholesterin ; in other
words, the substances wtich predominate in the white matter. As far as
they go, our results on the younger brains are in harmony with the work
of Kaes (35) on the influence of age on the myelination of fibres, but the
number of cases, especially senile cases, is not sufficient to permit of any
close correlation with his observations.

In connection with the changes due to age, it seems of interest to
compare a brain of lower anatomical development. A comparison of the
brain of the dog and human follow's: —

Table Til.

CoMPAKisox i)¥ Brain ok Him an and

Dog (1).

Hu.\i.vn (Case 19).

Wei gilt

... 75 grammes.

1,280 grammes.

Whole hniin.

Whole brain.

Protein S.

78

00

Lipoid 8.

18

27

Neutral S. ...

6

9-5

Inorganic S.

8

8

Protein P. ...

4.-5

4

Lipoid P.

70

73

Extractive P.

25’5

28

Moisture

78T

77-9

Total P.

1-50

l':>0

Total S.

0-45

0-50

206

ARLH1VL6

The agreement in the phosphorus is quite close. The variation in the
lipoid and neutral sulphur will be discussed at a later date when an
investigation of a series of brains IToiii dittereiit animals which is to b<‘
undertaken by one of us, has been completed.

Changes involved hy reason of the nature of the cause of death: —

The variations that may be introduced by post-morteni change have
already been discussed (p. 1S5). As a good many of the mental cases
here studied died of tuberculosis, it appeared of interest to compare three
normal brains, one of which was from a case of tuberculosis, the others
from cases whicli had died of other causes.

TaHLE IV. — CoMl’AKI.SO.N OF BkaINS OF (AsES 1)VIN(; FKOM J3lFFKKENT CaUSKS.

Case

16.

Case 10.

1 Cask 70.

1

Inffugn

CiiHfle ol Death...

Sion' llnoiinrrhofie

Tubtrculoflii

nupfjUT'ative

1 meuinpitis.

Cortex. 1

Corpus

caliosnni.

Cortex,

Corpus
eallosuiii. '

i

WhoK-

brain.

Whole brain

l*roti*iu S.

“tio

o(i

7.VO

00 1

!

8.

70 ■

My

70

i

l>7

[ •.*.!

Neutral 8. ...

10-0

V2V

i Oo

1»*5

s

Inorganic 8.

... 1 H

:)*5

1

o‘.J

Ill spite of the great difteience in the cause of death (a chronic, an
acute infection, and a simple loss of blood) the results are fairly uniform,
and are within experimental error. They also indicate that variations in
the amount of blood in the brain at death do not introduce an appreciable
error.

Changes Uiiserved in Mental Casks.

(a) The cases chosen were those in which a clinical diagnosis of
dementia praecox was given. The results are as follows:-—

Table V.— V'akiations in the Proximate Constituents.

! Cortex Corpus chIIo- uni.

Case lA

' Case 17.

Case Io.

Case 17.

Normal.

Dementia

Pnccox.

Normal.

Dementia

Praeco.x.

F’rotein ...

17-1

in-I

•J71

’8

Kxtractive.s

/ ■/

1

Ash

>4

'll

Lecithin and Kejihaliii

L>:co

:Jlt)

2P-7

Cerebri ns

8-8

1

18*3

20-2

The only change of any magnitude involves a decrease of the extrac¬
tives to which attention has already been drawn by one of us (36) in a
previous paper.

CHEMICAL EXAMINATION OE DRAIN

207

208

ARCHIVES

CHEMICAL EXAMINATION OF BRAIN

209

The largest percentage variation is found in the neutral sulphur. It
varies in the cortex of the two cases of dementia prsecox among them¬
selves, but in each instance it is lower than in the normal cortex. The
variations in the inorganic sulphates are of little value on account of
the small amounts, the estimations amounting in reality to a correction
only. The jHoportionate amounts of neutral sulphur are not mucli
greater, hut in order to confirm the results analyses were made on 100-
grauime samples of a minced hemsiphere.

The variation in the total sulphur and phosphorus are within the
limits of error. The largest variation again is the decrease of neutral
sulphur, and the next largest the increase of sulphates. The increase in
sulphates may not necessarily be of significance, as the actual quantities
were very small and consequently liable to analytical error; this, how¬
ever, was not the case in the neutral sulphur estimations. Although the
variations in the neutral sulphur of the pathological cases among them¬
selves are considerable, they are all in the same direction, and conse¬
quently of a consistent nature.

The absence of variations in the phosphorus fractions is striking.

(b) Dementia parali/tica .—This form of insanity was selected to serve
as a control of the analytical technique of the adolescent cases: —

Table Ylll.

Variations in the Proximate Coxstiti ents.

Cortex. ^ Corpus Callosum.

VyV/tVrUO V/ALiiA/OL'itt.

Case 15
Normal.

Case 16

G. P.

Case 15
Normal.

Case 16

G. P.

Protein.s ... ... ... ...'

471

50 7

27T

:!o-o

Extractives

7*t)

3*9

37

Ash .

5-0

0*0

i 2-4

Lecithins and kephalins

237

23-9

1 3PU

1

Cerebrins

8*8

9-4

18*3

! 18-2

There is an increase in proteins probably correlated to the growth of
glia tissue, a decrease in extractives in the cortex and a very marked
decrease in the lecithin and kephalin of the corpus callosum. The latter
decrease is not so well demonstrated in the following cases, in which
uniform samples of a whole hemisphere were analysed. However, there
is a tendency for the lipoid phosphorus to be decreased.

O

210

AIU'lllVKS

t^erves as a control of the analytical technique. Although the lipoid [diosphorus lias a decided tendency to be decreased
with a corresponding increase of the extnictive phosphorus, the variation is not so striking as might be expected. The
increase in nuclein phosjihorus observed by one of us (W. K.) and Goodseii (37) is apinirently not present in all cases.

CHEMICAL EXAMINATION OF BRAIN

211

(c) Other cases of mental disorder ,—As a further tOvSi of the metliods
two mental cases witli the clinical diagnosis of melancholia were taken
for analysis. The results are given in tlie following table: —

'Paulk X.

CoMPAKLSON OK TIIK BUAINS OF 'I'WO XoKMAI. ( 'ASKS AND 'Pwo ( ’asKS OF M K1,ANCHOLlA.

1

1

j

Normal. j

Case IS, j Case 70. j

Melancholia. j

Avkragi?:s. I

Percentage

Variation.

Case 25.

Case 20. |

Normal. |

Patho- 1
logical.

Protein 8.

62" 0

1

1 r,7-4

!

^7-2

- 7-0

Lipoid S .

•JH’t)

; 2ir7

;52-4

27-2

:no

4-13-9

Xeutral 8.

1 ■-

8-1

1

7-()

7 7

8’1

4- 5-2

Inorganic 8.

2-4

—

- ■

Protein P.

•)’7

4-2

41

4*8 1

4-2

- K/O

Lipoid P.

71-8

7;.-0

6ir2

74*7

i

72-0

- 2-(»

Extractive P.

24-2

1

1

2645

21-2

21*8

23*9

4-10-0

The variations are comparatively slight, and permit of no conclusions
that would not be vitiated by differences due to the material or the
analytical technique. The sulphates were not estimated in the two patho-
logical cases, and the neutral and protein sulphur correction was applied
according to the results of other cases.

Experimental Changes (with Dr. E. H. Pike).

As the results in dementia praecox might be interpreted as representing
a reduced oxidation, some experiments were undertaken with Dr. ¥. 11.
Pike, of the University of Chicago, to study the effect of cutting off the
four arteries (two carotids and two vertebrals) from the brain of a dog. As
Mott and Hill have shown (38), if the animal recovers at all from the
operation the recovery is complete. Such proved to be the case in the
cases of which the analyses are given in the following table : —

'Paplk XI.

Dug (2)

Do(i (3)

VVeiglit of brain 46-bH gramme.^.

•M as oraninies.

3 days after operation.

2 months aft(*r ()])ei*atioi

Protein 8.

. 73-9 .

73-9

Lipoid 8.

. 16-1

16-0

Neutral 8.

. 7-1

hV

rnorganic

< 2-9

.*.o

The first case serves as a control, for it is hardly likely that an organ
which has such a special m(‘tabolism as the brain would change in a few

0 3

212

AECHIVES

(lavs. The results show no variation at all, anil {^ive a very g*oo(l idea of
the aceuiaey to be expected from tbe methods outlined in this paper.

1\^ Description of Casks.*

Case 13. —S. U., Evelina Hospital, London, T/ll/UG. Female; age six
weeks. Autopsy 24 hours after death.

Weight of hrain. —G40 grammes. White matter had not differentiated
sufficiently to be capable of microscopic separation. Whole right hemi¬
sphere, after removing basal ganglia, used for chemical analyses. On
account of the premature birth this brain is very much under developed
for its age.

Cause of death. —Prematurely born ; died from inanition.

Case 14. —E. McC., Evelina Hospital, London, 8/12 UG. Female, age
1 year 11 months. Autopsy ten hours after death.

Weight of hrain. —1,100 grammes.

Cause of death. —Exhaustion following (two days after) operation for
umbilical hernia. No evidence of peritonitis.

Case 15. —B. A. G., Dept, of Path. Univ. of Chicago. 199 M. March
7tli, 1907. Male, age 19 years. Autopsy seven hours after death.

Weight of hrain. —1,670 grammes. No wasting; no excess of fluid.
Very anaemic. The Betz cells are perfectly normal. Many of the cells
of the other cortical layers are somewhat swollen (cell body and nucleus),
and show slight chromatolysis. The change is similar to the one observed
experimentally with lack of oxygen. In no case, however, is there any
gross change. The cells of the prefrontal area appear to be normal.

Cause of death. —Haemorrhage from right internal carotid artery,
following erosion by peritonsilar abscess. Death occurred as a result of
continuous bleeding two days after onset.

Mental state. —Normal and of good order of intellect.

Previous occupation. —Student in high school.

Case 16 .—C. T., Claybury Asylum. 4G.M.0G/2. Male, age 46 years.
Autopsy 24 hours after death, body kept in cold chamber.

Weight of hrain. —1,230 grammes. Much wasting, large excess of
fluid. In the prefrontal region great destruction of nerve cells. Vessels
greatly thickened. Marked neuroglia proliferation and all characteristic
changes of general paralysis.

Cayise of death .— Acute pulmonary tuberculosis.

* NinnlH'rs in (‘oni imiat ion of previously publi^lu**!.

CIIKMICAL EXAMINATION OF 13RAIN

213

Diagnosu of taaUal state, —General paralysis of the insane, witli pro¬
gressively slow dementia.

Frevious occujjaiion, —Labourer.

Length of time in Asylum. —Seven months.

('ase 17, —H. ¥. K., Claybury Asylum. 3G.M.0G/2. Male, age 20
years. Autopsy nine hours after death.

Weight of brain. —1,G45 grammes. Excess of cerebrospinal fluid
(S-=18 parts per million; P=1G0 parts). Some wasting. The nerve cells
(except tlie Betz cells) throughout the cortical layers in ascending frontal
and parietal region, except for a little swelling, are normal. Most of the
Betz cells in the ascending frontal are somewhat swollen and show definite
chromatolyais, most often perinuclear. Some of the Betz cells are quite
normal. The neuroglia cells are swollen and show some evidence of
recent proliferation.

Cause of death.—Fulmowdi'y tuberculosis.

Diagriosu of menkd state. — Dementia Tra'cox.

Previous occupation. —Erench polisher.

Length of time in Asylum. — 2^ years.

Case 18, —A li., (fliaring Cross Hospital, London. M./OT. Malt‘, age
49 years. Autopsy 17 hours after death.

Weig/it of brain. —1,270 grammes. No wasting. Nerve cells normal.
Some proliferation of the blood vessel walls.

Cause of death. —Pulmonary tuberculosis.

Diagnosis of mental state. —Normal.

Previous occupation. —Commission agent.

Case 19. —W. D., Brompton Hospital, London. M./07. Q.p.31.

Male, age 24 years. Autopsy 19 hours after death.

Weight of brain. —1,230 grammes. Convolutional pattern good. No
wasting. Most of the neiwe cells are normal, although a considerable
number show' chromatolysis, without mucli destructive change. Some
Betz cells show' chromatolysis which is generally perinuclear, and
resembles that observed in dementia prsecox. There is some slight
vascular and netiroglia proliferation.

Cause of death.--Vnlmonary tuberculosis. Duration of disease 18
months, in hospital three months.

Diagnosis of mental state. —Normal.

Previous occupation. —Printer.

Case 20. —A. C. C., vSt. Thonias's Hospital, London. M./07. Male,
age IG years. Aiito]>sy ‘iO liours after death, body kept in cold chamber.

Weight of brain. —1,440 grammes. No wasting. The nerve cells in

AIU’IIIVKS

214

pyruiiiidjil luytM* aio very irro^ulurly arranged, a fair number show
various stages ot cbroiiuitolysis, but most aie of normal appearance.
There is also some evidence of destriietive change in the cells of the
pyramidal layer. The Betz cells show less change than those of the
previous case. The vessel walls are thickened, and there is a moderate
amount ot vascular and neuroglia proliferation (more than in Case 19).
The pia is swollen and thickened and the vessels of the pia and cortex
generally are congested. On account of the histological appearance the
case might be mistaken for early (j. B. (Dr. Helen Stewart).

Cause of death. —Tuberculosis of lungs and intestines. Two months in
hospital. History of tuberculosis in family.

Diagnosis of vicntal -Normal. Physiognomy of a low type.

Previous occupation.— Hall boy.

Case 22. —E. J. B., Claybury Asylum. 12d.M.07. Male, age -37
years. Autopsy four hours after death.

Wtight of brain. —1,190 grammes. Micn)scopie examination revealed
characteristic changes of general paralysis.

Caust of death. — Exhaustion of Cj. P. 1. Congestion and mdema of
lungs.

Diagnosis of mental state. —General paialysis of the insane.

Previous occu pat ion. —Plumber.

Tjtnglh of time in Asylum. Eiftc‘en months.

Case 2o. —M. A. P., Claybury Asylum. 5.E.0712. Eemale, age 40
years. Autopsy 17 hours after death.

Weight of brain. —1,055 grammes. Some general wasting. ilicro-
scopic examination revealed characteristic changes of G. P. 1.

Cause of death.—Xi^wie pulmonary tuberculosis.

Diagnosis of mental slide. —General paralysis of the insane.

Previous occvjiation. —I'ur hand.

Length of time in Asylum. —Two years nine months.

Case 24. —C. B., Claybury Asylum. 6.r.07/2. Eemale, age 44 years.
Autopsy one hour after death.

Weight of brain. —1,055 grammes. Considerable wasting. Micro¬
scopic examination revealed characteristic changes of G. P. I. Large
number of seizures before death.

Cause of death. —Exhaustion of seizures of general paralysis.

Precious occupation. —Laundress.

Length of time in Asylum. —Six years.

Case 2o. —A. B., Claybury Asylum. 128.M./()7. Male, age JU) yours.
AiitojKsy 28 hours after death.

CHEMICAL EXAMINATION OE BRAIN

215

Weight of brain .— 1,275 grunmies.

Cause of death. —Acute puluionary tuberciilosi.s.

Previous occupaiion .—Pain ter.

Diagnosis of mentid state. —Melancholia. Probably congenital imbecile
with epilepsy. Began to have epileptic fits at 14. Threatened to commit
suicide.

Length of time in Asylum. —Five years six montlis.

Case 26. —I. E., Claybury Asylum. 7.F.07/2. Female, age dS.
Autopsy 40 hours after death, body in cold chamber.

Weight of brain. —1,020 grammes. Some general wasting.

Cause of death. —Pulmonary tuberculosis.

Diagnosis of mental state. —Recurrent melancholia.

Previous occupation. —Hawker with her husband.

Length of time in Asylum. —Has been in asylum three times since 1804.
Resident for eight years prior to death.

Case 26. —M. R., Horton Asylum. 4/1 08. Female, age 17 years.
Autopsy five hours after death. (Brain sent to Claybury and placed in
cold chamber. Forty hours elapsed before material was collected.)
Weight of brain. —1,075 grammes.

Cause of death. —Tubercular salpingitis. Tuberculosis of lungs, in¬
testines and left elbow joint.

Diagnosis of mentid state. —Dementia priecox (Uatatonic stupor).
Previous occupation. —General servant.

Length of time in Asylum .—Three montlis.

Case 29. —C. H., Bexley Asylum. 2/8/08. Male, age 23 years.
Autopsy 26 hours after death.

Weight of brain. —1,165 grammes.

Cause of death. —Lobar pneumonia. jNo tubercle.

Diagnosis of mental state. —Dementia prjecox.

Previous occupation. —Labourer. Reached onlv lYth Standard at age
of 13.

Length of time in Asylum. —Four months, twenty days.

Case 30 .—W. C., Rainhill Asylum, Liverpool. 2,471. AI., June/07.
Male, age 23 years. Autopsy 30 hours after death. Body not kept in
cold chamber.

Weight of brain. —1,435 grammes. Some general wasting in pre-
fn>ntal region. Brain cedematous, considerable excess of fluid.

Cause of death. —Marasmus. No tubercle, lungs healthy.

Diagnosis of mental state. —Dementia priecox.

Previous occupation .—Packer in factory.

ARCIIIVKS

•21G

Case 40. —il. Jv (i., Clavbury Asyluiii. ol.l\/U8. I'emale, age 47
years. Autopsy tliree hours utter death.

Weight of brain.. —!)55 grammes. Jt liemisphere 42U grammes,
L hemispliere dUU grammes. Tlie brain was extremely wasted and much
congested, especially tlie L hemispheie, wliicli was taken lor analysis.
Microscopical examination revealed tlie clmracttuislic changes of general
paralysis. Patient liad seizures on and oil since admission, more severe
and frequent six months prior to deatli.

Cause of death. —Acute lobar pneumonia.

Diagnosis of nuntal -General paralysis ol the insane.

Previous occupation. —Housewife. Married.

Length of time in Asglum.-- Eight j'ears.

Case 41. —M. D., Horton Asylum. 19/2/08. Female, age 28 years.
Autopsy 18 hours after death.

Cause of death. —Tuberculosis of lungs and intestines.

Weight of brain. —1,095 grammes.

Diagno.'ii.i of ment(d state. —Dementia priecox.

Previous occiKpation.- Wdrii^di. Housewife.

Ijctigth of time in A.'^f/luni. —Three years nine months.

Case 42. —C. O'C., Horton Asylum, d/d 08. Female, age 27 years.
Autopsy 13 hours after death.

Weight of brain .— 1,190 grammes.

Cause of Jeffth. —^lorbus cordis. Fatty degeneration. Bronchitis.
So tubercle.

Diagnosis of mental state. —Dementia praecox.

Previous ocrujnifion. —Domestic servant. Single.

Length of time in A.njlum. —Four years eleven months.

Case 70 .— J. E. S., Department of Pathology, University of Chicago.
1/5/08. Male, age 43 years. Autopsy 4-5 hours after death.

Weight of brain. —1,400 grammes.

Cause of death. —Diffuse suppurative meningitis. (Duration of illness
one week.)

Mental state. —Normal.

Previous oceupation. —M.D. Surgeon.

Summary.

iletliods liave been devised and a?*e given in detail (1) for the estima¬
tion of the i^roximate, constituents of the brain, and (2) for the estimation
of tlu* elements ]>hosphorus and sulj)h.ur in the various groups of con¬
stituents: pr(>f»*in, lipoid, neutral and inorganic sulphur; protein, lipoid

chemical examination oi' BEAIN

•ar

uiicl extractive pUospiiorus. Preliminary analyses have been made in a
lew cases on the grey and white matter separately. On account ol the
small quantities ol tJie elements actually present in the brain, these
analyses have only been regarded as of value when the analysis of a
100-gramme uniform sample of the whole brain yielded confirmatory
results.

The methods have been employed for the analysis of 20 brains from
normal and pathological cases, with the following results; —

(1) Analysis of the brain at different ages shows that with the growth
of the brain tliere is a decrease in the amount of moisture, proteins,
extractives and ash; and the cerebrins, lipoids and cholesterin increase.
Also there is an increase in the lipoid sulphur and phosphorus and a
decrease in the neutral and inorganic sulphur and extractive phosphorus.

(2j Differences may be determined in the brains of different species,
as demonstrated by a comparison of the human brain wdth that of the
dog. This subject will be discussed by one of us (W. K.) at a later date.

(d) Comparison of brains from cases in which the causes of death
were of an entirely different character showed no variations of importance.
As the cause of death in one of these cases was “ htemorrliage due to
erosion of peri tonsil ar abscess,” it is apparent that the amount of blood
present in tlie brain at death does not introduce any error of importance.

(4) Six brains from cases of dementia prajcox have been ex¬
amined, four by analysis of a uniform sample of the whole brain,
and two by analysis of the grey and white matter separately.
The results obtained on three cases already published (13) in
which the analyses were made on the grey and white matter
separately have been confirmed. Compared with the normal, the
amount and distribution of 2 )liosphorus shows no mark.'d change, liit
the neutral sulphur shows a great diminution wliile the inorganic and
protein sulphur is relatively increased. Thus so far, nine cases in all
have been examined and found to give results which, although varying
among tliemselves, all tend in the same direction,.t.^., a diminution of the
neutral sul'phur. This variation appears to be independent of the cause
of death and so far has not been found in other forms of insanity. It
does not seem then unreasonable to suppose that the subjects of this
mental disorder may possibly possess a general bodily inherent deficiency
for oxidation processes. Examination of other tissues of the body for
neutral sulphur and its proportion to the total sulphur contents would
help materially to decide this point. In the meanwhile some support to
this view of a general inherent bodily deficiency for oxidation processes
is afforded by Pighini’s observations on the inciease of neutral sulphur
in the urine in this disease.

218

AUCUIVES

Fli'i Itraiiis liom cases of i;eii(?ial paralysis have beeu examined,
four by analysis of the brain as a whole and one by analysis of the white
and gTey matter separately. These cases were selected as controls of the
analytical technique for the dementia pra^cox cases. 2^hey do not show
funj marked chanqe in the neutral safjdiur conUiut of the brain. Compared
with the ]iorma], the results show that the destructive changes in this
disease affect tlie brain generally and not one constituent in particular.
There is, however, a tendem^y for the lipoid phosphorus to be decreased,
indicating a gi^afer destruction of the ])hosphatids.

The application of these methods to the study of other tissues seems
quite promising, and will be taken up in the course of time in the
laboi’atories from which these observations have been reported.

In conclusion, we would express our indebtedness to the Pathological
Sub-Committee of the London County Council for the many facilities
afforded to us, and to Dr. F. W. Mott, F.E.S., for his valuable suggestions
from time to time, and aid in obtaining the large amount of varied
material, without which the work could not have been done.

Also we would thank the many gentlemen to wliom we are indebted
for normal and pathological material and clinical histories. Dr. Geo. A.
Watson and Dr. Wells have kindly aided us with material and histo¬
logical reports. Mr. H. C. Corper has assisted us with some of the
phosphorous estimations.

The investigations were assisted by grants from the Rockefeller Insti-
tu<e for ^fedical Research.

REFEEENCES.

(I) K()(;h, W. a lUmt'oii Jinn'ind ()f xi., p.

(’2) Folln mul SiiAKKKU. Ainrrican Journal of Itisun Htj. lx n 700 and Ixi

p.20U.

(2,) Richards and Wallace. Journal of Bioloifiral ChemUinj, 1908. iv.. p. 179.

(4) Mott and Halliburton. “ Phil. Trans. Roy. Soo. exci.” 1899, cxiv., 1901.

(o) Mann, G. “ Physiological Histology, ^fethods and Theory.” Oxfoi’d Ihvss, 1902.
(0) Mott, F. W. “Archives of Neurology.” Vol. iii., 1907, p. 218.

(7) HALLlBURTf)N. Collected papers of Phvsiological LaboTTitorv. King’s College

London, 189;j, No. 1. ‘ ^ ’ ""

British Medical Journaf 189.^. Goulstoniaii Lectiire.s : also Ergehnis.se dei* Physiologic
1905. iv. p. 31.

(8) SciiKARiN. “ Inaugural Dis.sei-tation.” St. Petersburg. 1902.

(9) Le\ ENE. “Archives of Neurology and Psycho])athology,” 1899. v. ii. p. 1.

(10) KOiink and (’hittenden. “ Zeitschrift t’ur Riologie,” 1890. xxvi., p. 291,

(II) Thudu iiu.m. . 1 . W. L. “ Die Chenhsche Konstitution des Gehirns des .Mcnscluui

und der Tiere,” 190l. F. Pietzcher. Tiibingen.

CHEMICAL EXAMINATION OF BUAIN

•219

(1l^) (iulkwitsch, W . " Zeitscliiii't t'iir l*syclH)l()^isciK* \xvii., p. x \.

(E)) Ivocn, \V. ** Zcitsclirift tiir IMiysioloi^isclic* (Mieniii*.’’ H»o7. liii.. p. VM).

(1-1-) BKIK(iKi{. .hihrcslKMiclit iiluT die Foi tsclu'itre dei' 'riercheiiiie.’* lHH|. xiv.,
p. 1^2.

(15) Koch. W. “ Zeirschrift tiir IMiysiolo^isehe (’lieniie,” xxxvi., p. Id4'.

(Id) 'rniEKFKLHKK, H. ** Zeitschiitt 1‘iir IMiysi()loL!:is( lie (’lieHii(‘.’’ H^oo, xxx.. ]). 549;
UH)4, xliii,, j). *21.

( 17 ) Hethe, a. “ Areliiv fiir experiiiieiitelle Pharinakolo^ie iiial Patholoi^ie,” 190 * 2 ,

xlviii., p. 78.

(18) BOn/.. “ Zeitselirilt tiir IMn siologische ( dieiuie.’* 1905, xlvi.. p 17.

(19) Tkhb M.C. Jon nidi of I*lty^idlo<jij, 11*00, xxxiv'., p 106.

(*20) Hallf lU'HTON. “ Ammal Report of (Mieinical Society,” 1907. iv., p. 25o

(*21) Leskm and Gies. Anirrinm Jonnial rf /*Jiysiolo(/y, 19o2, viii.. p 1S:J; ;ds(» 77/c
Jounidl of Bioloijii-dl ( linnislry, 190.5, i., p. 5.

(2;^) Rosenheim and 'Tehk. Jonmul (f Phyxiohufij, 1907, xxxvi., 1. p. 1.

(29) (OiAMEK, W. .hoir,idl of I^hyxiologif. 1904, xxxi.. j). 9)0.

(*24) Ckamer and Lockheah. Biorlwmiral JonrndL 19o7. ii., p. 9»5o.

(2.5) Koch and Mann. (Rroc. Pliysiological Society.) Jonrnnl of Bhyxiolotfif. \'ol.

xxxvi., 19o7.

(*26) Koch and Reed. Jonniol of Bioloyirol C7/c]/^/5</r//, 1907, iii., p. 49.

(27) Heffner. Mnliriii.isrh’UiiAurunssiyiiHrJdfBii h Arrhiv, 1907, i., p. 81 i also“ Arcliiv

fur experimentelle Pathologie und Pharinakologie,” 190S. Supplement Band
Si'Jimicdeheri/it FestsrhrifL |>. 253.

(28) Grindlev and Woods. The Jonrndf <f Bioloyirdl Chon Is!ry, 1907, ii,. p. .909.

(29) Folin, 0. The Jonnotl of Bioloyind CJo inistry, 19o5, i., p. 191 ; 19o7, iii., p. 81.
(.30) Koch and Woods. The Jniininl of Bioloyiml Chonisfry^ 1906, i,, 20:').

(91) Grindley. Jountdf (f thr A nieriron (■heinirol Sor 'd iy^ 1906, xxviii.. p. 51.

(92) BenedikTv I'hv Ainrriron Jonrndl <f Bhysioloyy. 1905. xiii., p. :{o9.

(9:1) Ritter. “ Zeitschrift fiir Physiologische Cheniie,*’ 1901, xvxiv., p. 4.56.

( 94 ) Hill, L. Jovniol of Phyxioloyy, 189 . 5 , xviii. p. 9 :) 4 .

( 9 . 5 ) Kaes, T . “Die Gros.sliirnrinde de.s Menschen in iliren Massen nnd in ihrein

Fasergelialt.” Jena. 1967. Fi.scher.

(96) Koch, W. “Archives of Neurology,” 1907, iii., p. 9.91.

(97) Koch and Goodsen. ^Inn rirdn Jonmol of Bhyxittloyy. P.mh;. xc., ]). 272.

(t)8) Mott, F. W. “Ci*oonian Lectures,” 1900, p. .50.

(99) Rosenheim and 'rERB. Jon nnd (f JdiyxuJoyy, 19o8. xxxvii.. p. 94<8.

THE ORGANIC METABOLISM IN DEMENTIA PRH^COX.
(Calorien, Albumin, N-total, Xanthin Bases, Uric Acid, Urea, S-acid, S-neutral.)

Fh' GIACOMO PIGHTNI.

(From the Scientitie Tjaboratories of the Institute of Psycinatry, Repfjio—Emilia.)

Note I.

Kraepelm was the first to consider dementia prajcox as a morbid
syndrome associated with profound, but indefinite, modifications of the
organic metabolism. A large number of communications have appeared
regarding the clinical symptoms of the disease, but very little has been
done to discover the metabolic disturbances which accompany these
symptoms, in a scientific manner following the work of Bischotf, Voit,
Pfiiiger and llubner.

In the metabolic experiments described in this communication 1 have
followed the methods of the above-mentioned authors and Imve quanti¬
tatively estimated the metabolism of different food elements in my
patients, making analyses of these substances when introduced in known
quantity into the organism and of their products when excreted.

For the experiments I have used a diet comprising bread, milk, lean
beef and eggs, in which the nitrogen, albumen, fat and carbohydrates
were quantitatively estimated. The patients were kept in bed during
the period of the experiment and watched in order that none of their food
or excretions were lost. The nitrogen and fat were estimated in the
fieces, desiccated after solution in water acidulated with sulphuric acid.
The total nitrogen, urea, uretic nitrogen, xanthin bases, uric acid, total
sulphur, and the acid and neutral sulphur were estimated in the urine.
The number of heat calories acquired by the organism was calculated
from the quantity of fat and albumen assimilated by means of the known
factors of Rubner.

I chose for my experiments patients in the acute and advanced stages
of the disease. The results obtained in the two types presented marked
differences, as is showm by the following experiments on four chronic
and tw-o acute cases of dementia praecox.

•DEMENTIA PRiECOX. Advanckd stage.

METABOLISM IN DEMENTIA PR.ECOX

22

14-2-2

li.—DEMENTIA l^R^iCOX. Acute stage.

236

ARCHIVES'

Ohscrcation VI. —F. E., aged 29 years. Duration of experiment 7 days. Tiie temperature varied from C. to 37*1° C.,
and the pulse from 80 to 85. Weight 04 kilos. Average daily yield of fmces 16*1 grrns. (desiccated), containinir
0*782 grma. nitrogen and 4*37 grms. fat.

P

o

228

AliCHIVKS

Tliu prec*c*iliiig tables show that two diilereiit alterations of the organic
metabolism are present. In the acute stage of the disease the organism
is subjected to a destruction of its own albumen as evidenced by the
increased excretion of nitrogen and sulphur in the urine, and notwith¬
standing the fat lost in the faeces (24 to 27 per cent.) the heat used by
the body is in excess of the supply. In the more advanced forms, how¬
ever, tlie excretion of nitrogen in the urine is diminished, for a good part
of the ingested nitrogen is lost in the fasces, so that only 80 to 90 per cent,
of the albumen is absorbed. If we add to this the loss of fat in the faeces
(varying between 20 to 25 per cent.), the assimilated calories become
much less, and we may consider that 5 to 6 per cent, of the heat produced
is not utilised.

In both phases of the disease the excretion of sulphur in proportion
to nitrogen is increased and there is also an increased excretion of xanthin
bases. These two facts might be associated with an abnormal destruction
of the nucleo-proteid of the organism. Clinical examination of the
abdomen failed to show alterations that would explain such anomalies
of the metabolism. Therefore, lacking more exact knowledge, we are
obliged to consider the change as being due to defective organic
chemical metabolism. This change, since it cannot be ascribed to any
external cause, may be considered as caused by an auto-intoxication.
In the first stage of the disease, the organism is subjected to a toxic
condition the cause and origin of which is unknown, and reacts to it by a
destructive proteid metabolism and by an alteration of its physical
functions. Certainly the toxin must be powerful, if gauged by the
marked destructive reaction of the tissues and the profound alteration
of the mental condition, w hich more or less rapidly progresses to dementia
and from which recovery is very infrequent. In the first four cases
observed the disease was rapidly progressive, and the dementia soon
became pre-eminent above all other physical symptoms.

The fact that, in the advanced stages of tlie affection, the nitrogen
and albumen either cease to be absorbed or to be excessively decomposed
indicates either an inadequate assimilation by the intestinal tract or a
cessation of the destructive organic metabolism. The heat metabolism is
no longer increased. The quantity of nitrogen and urea and the oxida¬
tion of the sulphur as sulphurous acid are completely normal. The facts,
excluding an alteration of tlie oxidising processes, lead us to tlie hypo¬
thesis that the intestinal and pancreatic juices, especially the latter, in
these patients have a deficient action. I may add in support of this that
there were muscle fibres and much fat in the faeces.

METABOLISM IN DEMENTIA Pll.ECOX

22!)

There are, liowever, two facts that still require explanation, and they
are (1) the augmented excretion of sulphur in proportion to nitrogen of
the urine, and (2) the increased excretion of xanthin bases. As shown
by the tables, these changes are common to both phases of the disease,
but are more apparent in the acute stage (Case V.). In both instances
we must infer that the nucleo-proteids and sulpliur-containing substances
of the organism undergo a destructive metabolism, and conclude that in
the more advanced period of the disease the auto-intoxication, though
less marked than in the early stage, is still active in the organism, and
in dementia praecox two types of an altered metabolism exist, one as the
result of the preceding acute phase, the other as the result of the disease
still continuing in a chronic form.

Note II.

(N, Nad, Ca, P, K, S.)

In the preceding observations I have attempted to show that in
dementia praecox, generally considered, two different modifications of an
altered organic metabolism may be distinguished. In some cases of the
acute disease, when the patients present symptoms of mental excitement,
negativism, impulsiveness, etc., the organism is subjected to a marked
destruction of its own proteid, which fact is evidenced by an excessive
output of nitrogen and sulphur compared w ith the intake; while
in the advanced phase of the disease, when dementia has developed and
the early symptoms—apathy, katatonia, and stupor and stereotypy—have
become permanent, a decreased assimilation and a lapse of the increased
nitrogen excretion are observed to occur.

To further confirm these preliminary experiments, I have undertaken
the investigation of the metabolism of the following inorganic elements—
sodium chloride, chlorine, calcium, potassium, phosphorus and sulphur.
The method adopted for each experiment was as follow^s: —The patient
w^as kept in bed during the period of the experiment and carefully
watched in order that none of the excretions were lost. A known quantity
of food was given. The food consisted of milk, bread, lean beef, eggs,
sugar, Marsala wine, coffee, table salt, and water, in w^hich the various

AECHIVES

2*j()

eleineiiis woio estimated several times. Table I. shows the percentage
coniposition ot the various diets.

Taislk I.

Kooi).

X. NaCl.

a.

(’a.

K.

s.

K.

Milk .

c.c. IfM)

0-‘.29

0-20

0-1.‘.78

01419

0-08-28

o-o:t:V.

0*14*20

Bread

. yr. KX)

±07

0t7K>

0-28<m

00108

0-1 :?5

0-O807

0-OK08

IJeot .

. g. lOlt

IMdH

Olll-

00151

0-3-2t)7

ov'ios

0-355

.

K-

2-087

0-21 :>

012!*1

0-0558

0-154

o-oloo

007 :?8

Marsala Wine ..

. c.c. loo

—

—

—

1 ,

— 1

o-o;j

—

Cotfee

. i-.c. KM)

—

—

1 -

—

0-0372

Water

. c.e. 100

—

' -

0-01

1

0*0048

j —

The urine

was analysed

every

24 hour.s (8 a.m.—8 a.m.), the faeces

were weighed immediately after evacuation, and the weight and number
of stools recorded. They were diluted and heated on a water bath, then
dried to constant weight at 100° C., and finally triturated and analysed.

I have studied the metabolism of these inorganic constituents in six
eases, two in the initial acute phase and four in the later chronic phase
of tlie disease. The first two recorded show the more interesting results,
which are as follows: —

2-52

AECHIVES

Is

o ^
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^ S e

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<N G1

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t. o ^ P-

INTAKE —Food. I OUTPUT— Urinb akd F.«oe.s. I B.ALANUE.

METABOLISM IN DEMEiNTIA PRAiCOX

2^];j

These two cases presented the disease in an acute form. In the first
case, now of five months’ duration, the primary attack ran a rapid course
to dementia, as evidenced by the demented habits of the patient after the
lapse of the acute pluuiomena. The second case is one of ten years’
duration, now suffering from an acute exacerbation. The period of ex¬
periment was during a time when the mental symptoms, having become
most marked, were diminishing in severity. Boih cases show the negative
balance of nitrogen, phosphorus, and sulphur. In the first case the large
loss fer diem of 8*393 grins, nitrogen, 0*811 grms. phosphorus, and
1*185 grms. sulphur is sufficient to lead to the conclusion that a patho¬
logical metabolic change exists. Case II. also presents this change, but
to a less degree. Figs. I. and II. show the relation of the nitrogen and
phosphorus in the food administered to that in the excretions represented
graphically, and illustrates the changes in the two cases better than
comment.

a

f

7

Jg_

H n a «v»l

!

is

B

B

m

B

B

B

B

B

t4

ts

it

n

r

It

a

<7

i.t

U

B

B

B^

B

B

B'

■

B

■

B

B

n

B

B

B

B

B

n

B

B

□

S

!9

m

la

s

iH

B

L

L

¥ui. I.

Via. II.

_N intake (food).

-H -h + + + 11 11

_N output (urine mid fjcces).

.P V

2:14

ARCHIVES

Table VI. shows the relation of the intake and output of the various
elements under consideration for both cases, taking nitrogen as a constant

= 100.

Tawly) VI

-

N.

1

Cl. :

i

Ca.

!

P. 1

8.

ObsGrrotioih /. —

Food

100

4J-27

r

12*45

10-71 '

3-96

Uriiio siiul fioces ...

100

10-20

t)'26

10-31

7*93

OJiserviilKtu U .—

Food

100

4006

9*13

4*49

Urine and lioffs ...

100

37*46

bU

10*03

7*62

It will be observed that the proportion of phosphorus to nitrogen in
the excretions is equal or nearly equal to that in the food, while the
proportion of chlorine and sulphur shows marked variations in the two
series, the chlorine being diminished and the sulphur being increased.

The only element that maintains a relative equilibrium of balance is
calcium, the results indicating that its metabolism is nearly normal and
independent of the other salts. If we compare the excretions in the two
cases we find corresponding figures except in the case of chlorine. The
latter may be explained by the difference in quantity of NaCl adminis¬
tered and also by the slowness with which this compound reassumes the
normal equilibrium.

The results in the case of nitrogen, calcium, phosphorus, and sulphur
in both cases show an identical balance. The observations are too few
to justify any conclusions correlating these variations with the clinical
features of the disease, but it is evident from the above figures that the
negative balance of N, P, and S is due in great part to a destruction of
the phosphorised and sulphurised proteids of the organism.

CHRONIC CASES.

MET.\B0L1SM IN DEMENTIA PE.ECOX

235

I

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o

RCIIIVES

Ohfirn-ation V. —S. L. Male, a^^ed 30 years. Tlie disease began sereii years ago with stereotypy, tics, labial tremors, copious salivation.
In a short time the patient became katatonic and the mental condition changed to dementia. For four years the left arm has
been contracted, the fore-arm flexed with clenching of tlie fist, l^he extremities present a certain waxen flexibility. Viscera

mktaholism IN dkmkntia m.^icox

239

In the last four cases (Icscribod the disease had become chronic, and
dementia was present. Outbreaks of excitornent had ceased, although
the other symptoms, hallucinations, mannerisms, katatonia, negativism,
echolalia, etc., forming the clinical picture of the disease, which had
remained unchanged for many years, still persisted. This chronic phase
is well distinguished clinically from the acute phase, and is characterised
by a special metabolism of its own.

In the four cases examined there is a loss of calcium and sulphur. The
results also show a retention of chlorine, but this is slowly returning to the
iicrmal equilibrium.

Figs. III., IV., V., and VI. represent the balance of nitrogen and
phosphorus in the four observations expressed graphically.

Fig. IJI.

Fig. IV.

Fk;. V.

■i- A -I-

Fig. VI.

N intake (food).

f P „

- N output (in-ine and frerea).

240

AKClllVES

It will be observed lliat the lines of the elements wlien introduced
into and when excreted from the organism run practically a parallel
course, which is not the case in Figs. I. and II. (acute cases).

Table XV. shows the relation of the intake and output of the various
elements under consideration, taking nitrogen as a constant = 100.

Table XV.

—

:

X.

!

Cl.

1

Ca.

s.

Observation Ifl —

Pood

loo

1

r,r,74

! '

(>-5:>

H'97

4 14

Urine and ficees .

ion

r>97:.

ll-i:;

905

8*58

Ohservniion TV .—

Food

loo

4-J 10

5<»6

«-0(i

470

Urine and faiccs ..

loo

870

804

Observation V .—

1

Food

100

: ddoO

6-U7

8'.5:>

4‘5(^

Urine and fjuces ...

lo<»

44;oi

774

8-Jl

Observation VL —

Food

100

5017

ti()0

8-H8

47:i

Urine and fjcccs ..

lOo

5:175

9-1 :j

8-94

1

8*91

The results show that the proportion of phosphorus to nitrogen in the
excretions is the same as that in the food, therefore we may conclude
that the retention has been in the same proportion. The proportion of
chlorine to nitrogen is also the same in the two series. The sulphur and
calcium, h(wv(*ver, in pixj^portion to the other elements in the series, are in
great excess in the excretions.

The excess of calcium is variable, but the sulphur in all four cases
maintains a proportionately high figure. The proportion ot X:P:S is
practically the same in the four cases. It would seem then that the
metabolism of these patients is characterised by a proportional retention
of nitrogen and phosphorus; by a proportional loss of sulphur and by
an independent varying loss of calcium.

It is also necessary to state that the water metabolism is changed.
With diflBculty the four patients were induced to .sw^allow' 300 to 400 cc.
of water which was added to their daily b od. Tt was estimated that the
food per diem contained about 1,200 cc. of water, thus every patient took
daily from 1,500 to 1,600 cc. and excreted in the urine and faeces 1,000

241

MKTAHOl.lSM IS DKMENTIA TUKCOX

to 1,400 cc. The researches of Pettenkofer and Voit* show that the
moisture perspired by the skin and lungs by a normal man in a state of
rest oscillates from 680 to 1,200 cc. in 24 hours, 60 per cent, passing
through the skin. Comparison with these figures shows that none of the
patients attained the lowest limit of moisture excreted by the lungs and
skin, the difterence between the intake and output of water (urine and
fsBces) being 300 to 500 cc. The excretion of moisture by the skin and
lung is therefore much diminished, and this would explain the relaxed
metabolism of the nitrogen and sulphur, and the imperfect heat meta¬
bolism—the sUb-normal temperature, etc., which are characteristic of
these patients. However, the organism may have contributed to the
excess of water in the urine and faeces.

This series of observations, although special attention has been paid
to the metabolism of the inorganic elements, leads to the same conclu¬
sions as the first series in which the organic metabolism (N—total, urea,
uric acid, xanthin bases, sulphuric acid, neutral S and total S) was
investigated, and in the two clinical syndromes of dementia prsecox
examined, two different modifications of an altered metabolism are
apparent. 1 may mention that the patients subjected lo the experiments
were chosen as typical examples of the two pluises. In the varied and
numerous cases of dementia praecox, probably there are many that present
a normal metabolism, and a priori it is probable that between the period
of remission or recovery from the acute phenomena and the varied symp¬
tomatology (also present in the chronic phase) that characterise the
disease, the metabolism of the subjects should have returned to within
physiological limits. To control these researches I subjected two cases of
dementia in perfect health to the same experiments. The metabolism in
these cases appeared to be absolutely normal except for a slight diminu¬
tion in the absorption of nitrogen and phosphorus.

Thus in all 12 cases, four in the acute stage and eight in the chronic
stage of dementia praecox, have been examined and have shown two
characteristic modifications of an altered metabolism corresponding with
the clinical syndromes.

The negative balance of nitrogen, phosphorus and sulphur, the exces¬
sive excretion of urea, uric acid and xanthin bases, with an accompanving
progressive decrease in weight, indicates that the phosphorised and sul¬
phurised proteids of the organism have undergone destruction. The tem¬
perature rises slightly, 37^ C. to 37 70 C., but this slight increase could
not account for this proteid destruction, for the observations of Linser and

PetteN’KOP’ER and Voit, Untersuchun^t'n iiber (len Stoffverbrauch des normalen
Meiischcn. /( itschrift fiir Btoloyie W. 459. 1806.

242

AUCHIVES

Sclimid show that a body temperature of at least 40® C. is necessary to
cause a dissolution of the proteids.

In the advanced phase the proportional retention of nitrogen and
phosphorus (as compared with the acute stage) indicates a decreased
metabolism, hut in spite of this retention the weight of the patients
fluctuates and often decreases. This fact may be explained, for while
nitrogen and phosphorus are being retained in the organism there is an
excessive excretion of calcium and sulphur. Moreover, it may be possible
that the excess of moisture excreted in the urine may influence the body
weight.

It is evident that in the urine of these cases there is an excess of
sulphur which cannot have been derived from the food administered,
and which must have resulted from the decomposition of some sulphurised
proteid. It is interesting to mention here that Koch,"^ at the suggestion
of Mott, submitted several brains of dementia prtecox to chemical analysis
and compared them with the normal brain. He found a marked diminu¬
tion of the neutral sulplnir (“ taurin-like sulphur’’) and an increase of
the inorganic sulphates. These results have been confirmed by Koch
and Mann {vidr p. 217) , who have found that this variation does not
exist in other forms of insanity, e.g.^ general paralysis, melancholia.

The results show an increa.sed excretion of calcium except in the fifth
case, in which the analyses were incomplete. The excess reached as much
as 58’4 per cent, over the intake (normal 5 to 10 per cent.), and appeared
to be most marked in cases with stupor of the kata tonic form.

Summary.

With a view of throwing light on the metabolic changes associated
with the profound symptoms of dementia praecox, I have selected four
typical cases of the disease in the acute and eight in the more advanced
stage, and in them I have studied the metabolism of the various food
elements by means of numerous analyses of the food administered and
the excretions. Each case gave results of interest, which may be sum¬
marised as follows:

(1) In the dementia pnecox of Kraepelin, the acute phase and the
advanced phase each present difi'erent modifications of a latered meta¬
bolism.

* Koch, W. Zeitsclirift, fiir I’hysiologische Chemie, 11^07, liii., p. 496.

metabolism in DEMKNTIA PR.ECOX

243

(2) In the acute phase, as evidenced by motor restlessness, sitophobia,
violent impulsiveness, slight elevation of temperature, etc., there is a
negative balance of nitrogen (urea, uric acid, xanthin bases) and of phos¬
phorus and sulphur, indicative of a marked dissolution of the phos-
phorised and sulphurised proteids of the organism.

(3) In the advanced phase, as evidenced by dementia, negativism, tics,
grimaces, katatonia, etc., there is a proportionate retention of nitrogen
and phosphorus, a loss of sulphur proportionate to these elements, and an
independent loss of calcium.

(4) In the two phases investigated there is an altered water meta¬
bolism, and a relaxed excretion of chlorine.

211

A BACTEEIOLOGICAL EXAMINATION OF THE CEREBRO¬
SPINAL FLUID IN DEMENTIA PRJiCOX.

Bv G. H. HARPER SMITH, B.A., B.C. (Cantab.), M.RC.S., L.R.C.P., and
RAE GIBSON, M.B., Gii.B., M.K.(\P.E.

(From tlie Putholofi^cal Laboratory ot the London County Asylums.)

Acting on the suggestion and advice oi Dr. Mott we have investigated
the cerebrospinal fluid withdrawn by lumbar puncture during life from
cases of dementia prsecox under treatment in the London County Asylum
at Claybury, paying special regard to the following points: —

1. The presence of micro-organisms.

2. The presence of protein, as evidenced by the Noguchi test.

d. The prebence of cells in the deposit of the centrifuged cerebrospinal
fluid.

Tecknig^^ut .—The difficulties that confronted us were {a) the poesibliiy
of air and skin contamination, and (6) the possibility of rendering the
cerebrospinal fluid sterile by the introduction of antiseptics. Our flrst
few experiments clearly demonstrated the great precautions necessary
to avoid air contamination. Dr. Candler, in his somewhat similar work
on general paralysis, has drawn attention to this source of error (vide
p. 145), and we have been able to confirm his observations by exposing
sterile culture plates to the air of the ward during the operation of
lumbar puncture; in several instances a luxuriant growth resulted. In
several cases also, befoie the skin was sterilized, we inoculated culture
tubes with scrapings taken with a sterile knife from the patient’s back near
the point of puncture; in many cases we obtained a growth of a coccus.

ITie method of procedure in the first five cases was a follows: —
The skin was cleansed with I in 200 carbolic solution, with subsequent
applications of turpentine and ether, and finally with 1 in 200 carbolic
lotion again. About 10 ce. of the fluid was withdrawn into a carefully
sterilized centrifuge tube, and the fluid was pipetted ofl into the follow¬
ing media: broth, blood serum, slope agar, and, for the purpose of
detecting any anaerobic organisms, glucose formate tubes were also
employed. The Noguchi test was made on 1 cc. of the fluid, and the
remainder was centrifuged and the deposit examined for cells.

THE CEREBROSPINAL FLUID IN DEMENTIA PR.ECOX

245

In spite of the precautions taken the first five cases showed growths
in three instances, the result of external contamination.

Cases 1 and 2 were sterile.

Case 3 show ed a cloudiness in the broth culture after 24 hours’ growth,
which on examination in hanging drop preparation was found to be a
non-motile organism, and on subculture proved to be the Bacillus Suhtilis.
After centrifuging, the supernatant ftuid of this case was incubated for
24 hours; it contained several organisms, including the streptococcus
and sarcinae.

Case 4 showed the presence of sporing organisms resembling sarcinae
in the agar and glucose formate cultures at the end of 24 hours, otherwise
the results were negative.

Case 5 showed a staphylococcus in the broth culture after subcultiva¬
tion on agar. The other tubes remained sterile. From the number of
diverse organisms which had been discovered we concluded that ihere
must be some fault in our technique. The frequent presence of an
organism resembling a mould convinced us that our precautions against
air contamination had not been sufficiently stringent. In the next two
cases therefore, instead of collecting the fluid into a centrifuge tube
and later pipetting it off into the different media, w^e allowed the fluid
to run directly from the needle -into the culture tubes. These two cases
show^ed a growth of streptococcus in both instances. The type of organism
forced us to the conclusion that the infection waa from the skin. We
therefore substituted mercuric cliloride solution for the carbolic lotion
in our technique. In the next four cases cultures of the cerebrospinal
fluid remained sterile. We recognised the possibility of the mercuric
chloride being carried in with the needle and thus causing a fallacy
in our results. To avoid this, after the skin had been cleansed as above,
we further removed all traces of antiseptic by the repeated application
of sterile distilled water.

Adopting this procedure, we examined 19 further cases, and in every
instance obtained a neqalive result.

Noguchi has described the following method for detecting protein
in the cerebrospinal fluid. One part of the cerebrospinal fluid is boiled
for a short time with five parts of a 10 per cent, solution of butyric
acid; one part of normal sodium hydrate solution is then added, and
the mixture again boiled. If the tube is allowed to stand for 30 minutes
to three hours, a coarse granular or flocculent precipitate denotes the
presence of a protein, which Noguchi regards as pathognomonic of para-
syphilitic affections. The presence of blood contamination renders the
test valueless. None of the 30 cases of dementia prsecox in which the
fluid was free from blood gave the test.

246

AACHIVSS

Conclusions .—^We have examined the cerebrospinal fluid withdrawn
by lumbar puncture during life in 30 ca«es of dementia praecox and
obtained a negative result in 23 cases after we had improved our tech¬
nique. We are therefore forced to the conclusion that the reported
discovery of any organism in the cerebrospinal fluid in dementia praecox
should be regarded with great caution, and in the light of the difficulties
we have encountered, we would suggest that any such organism may be
the result of external contamination.

As one would expect the Noguchi test for proteins yielded a negative
result in all fluids examined that were free from blood, and the examina¬
tion for cells in the centrifuged deposit of the fluid was also negative.

We would express our gratitude to the Pathological Sub-Committee
of the London County Council for the facilities afforded to us in proceed¬
ing with this work in the Laboratory, to Dr. Robert Jones, for the kindly
interest he has taken in our endeavours ; to Dr. Candler, whose previous
experience with similar work has enabled him to aid us with much
valuable advice; and to Mr. S. A. Mann for his constant kindness and
assistance.

247

NOTES AND OBSERVATIONS ON FORTY CASES OF NEW
GROWTH, INCLUDING EIGHTEEN INTRACRANIAL TUMOURS *

Examined in the Pathological Laboratory of the London County Asylums,

Clay bury,

By Helkn G. Stewart, M.D.

In the following paper the notes are given of 40 cases of tumour,
examined consecutively in the laboratory of the London County Asylums
at Claybury. Permission to work in the laboratory was kindly accorded
by the Asylum Committee, for which privilege I am mueli indebted.
Through the kindness of the Director, Dr. Mott, who placed at my dis¬
posal the cases of cerebral tumour which were sent to the laboratory for
examination from all the London County Asylums (also a case under his
care in Charing Cross Hospital, and one case of tubercular disease of the
brain from the Children’s Hospital in Great Ormond Street), I have had
the opportunity of examining 18 cases of cerebral tumour, and, in addi¬
tion, 22 cases of new growth of other organs occurring among the
patients at Claybury Asylum. Of the latter, 21 were from 'pod-mortem
material, and one a breast which was amputated. The nature and
])osition of the growths were as follows: —

4. Gliomata

2. Sarcomata

5. Endotheliomata

2. Adenomata V Intracranial (L owths.

3. Syphilitic

1. Tubercular

1. Cancer

6 Cases of cancer of the stomach.

4 Cases of cancer of the breast.

2 Cases of papilloma of bladder.

1 Case of cancer of the lungs.

1 Case of cancer of the intestine.

1 Case of cancer of the bladder.

1 Case of cancer of the suprarenal gland.

1 Case of adenoma of the suprarenal gland.

1 Case of adenoma of the thyroid gland.

1 Case of adenoma of the kidney.

1 Case of adenoma of the prostate.

1 Case of fibroma of the ovary.

1 Case of cancer of the uterus.

* Being part of a Tlicsis prescntetl f<»r the M.D. degree of the Birmingham University,

June, 1908.

248

ARCHIA^ES

The investigation was suggested by the discovery of cell inclusion,
somewhat similar to those met with in cancer in the tissues of animals
and human beings suffering from trypanosome infections. These cell
inclusions were seen in the glands of dogs who had been inoculated with
the Trypaywsortia equiperdum, and in the brain and glands in cases of
sleeping sickness. The tissue in which they were demonstrated was fixed
in Muller’s fluid, mordanted in an aqueous solution of iodine in potassium
iodide, and stained from 5 to 12 hours in a 10 per cent, solution of
Giemsa’s stain at a temperature of 37°C.

When sections of cancer tissue were stained by this method, after
fixing either in Muller’s fluid or in Formalin in normal salt solution, it
was found that the so-called ‘‘inclusions” were differentiated from the
cancer tissue cells, and thus their form and distribution could be more
easily studied.

Many other methods were also employed in studying these growths.
Hanging drop specimens were made in many instances, and watched on
the warm stage. Film preparations were made stained by numerous
methods, but the best results for studying the inclusions were obtained
by a modification of the “wet” method of film fixation. Thin films were
exposed for about 30 seconds to the emanations from Thorium Nitrate,
^then mordanted in iodine solution and stained by Giemsa’s fluid (50 per
cent, in warm aq. dest. for 10 to 20 minutes).

By this means the atypical pink cells were first seen in the film
preparations of a gliomatous tumour.

Zenker’s and Fleming’s methods of fixation have also been used for
ti.ssues in hulk, and acetic acid and alcohol, but with less good re¬
sults. Sections have been stained by all the usual methods, including
polychrome methylene blue, Heidenhain’s method for glia tissue, etc.

The chief points which it has been my endeavour to investigate in the
present research are: —

(1.) The origin and method of spread of the growth ,—Under this head¬
ing the result of my examination supports the view that some tumours at
any late do not originate in a single cell or group of cells. Evidence of
tin’s was first noticed in gliomata, where a diffuse tendency to multiplica¬
tion can be se^m in the neuroglia cells over large areas.

(2.) I'hc origin and distribution of certain atypical cells, —These cells,
which have been described by many authors, were investigated by the
modification of the Giemsa method mentioned above (which for brevity
will, in future, be designated the I. G. method). It is held that these
cells have a wide distribution, that they occur on the surface of the
epithelium in both early and advanced cases of cancer of the alimentary
tract; also free in the lymphatic vessels and spaces around the vessels

NOTES ON FORTY NEW GROWTHS

249

in plionuda, and may be seen invading the tissues in secondary growths
without the intervention of the cancer cell proper.

It is suggested that these cells, whatever their origin and nature may
be, are taken up by the epithelial cells as foreign bodies, and in this way
engender the infiltrating habit of the malignant tissues.

(3.) The cell reaction and changes .—The lymphocytic infiltration in
cancer has for long been recognised to be irregular in distribution. It
has recently been contended that this small round cell reaction is due to
mechanical irritation, and, therefore, it has seemed worth while to note
that in these growtlis (especially noticeable in those f)f the brain), the
lymphocytic infiltration appears to be perivascular, and not confined to,
or necessarily connected with, those vessels which are distended by, or
infiltrated with tumour growth.

Cam 1 .—Clioma of iJic. frontal reyioti of the left Cerchral Heviii^jiliere.

J. C., aged 70, on admission had defective memory and hallucinations; later
developed a tottering gait and some paralysis of the right side; became demented
and died in a seizure.

Post mortem .—There was some atheroma of vessels and cardiac valves. The
dura mater was adherent to the calvarium; the pia mater was thickened and
there was some excess of cerebrospinal fluid, llie whole of the anterior portion
of the left cerebral hemisphere was occupied by a circumscribed mass, reaching
from the anterior pole to the genu of the corpus callosum. It was yellow in colour
but contained red areas suggesting luemovrhage, and some parts of the periphery
presented the appearance of yellow softening. The condition suggested some form
of neoplasm which was undergoing a regressive metamorphosis. At about the
middle of the central sulcus of the right Island of Reil was a definitely circumscribed
pigmented spot about 5 mm. in diameter.

Microscopic examination .—Sections taken from the edge of the tumour showed
degenerating tissue, in some places continuous with proliferating glia cells, in
others cut off by fibrous strands.

The normal structure of cortex and medulla was replaced by proliferating glia
tissue, and this was thickest and most cellular near the degenerating areas. The
vessel walls were thickened and those within the growth were surrounded by dense
fibrous tissue. Many of the vessels were thrombosed and some organised. There
were numerous hpemorrhages and in some parts a well-marked lymphocytic infiltra¬
tion. In sections stained by the I. O. method some cells, with protoplasm taking
a clear pink stain and with dark almost black nuclei, were seen among the pro¬
liferating tissue around the vessels. The cortical nerve cells were disorganised and
undergoing phagocytosis near the growth. The glia tissue showed proliferation for
some distance away from the tumour area proper ; it was well marked bi the cortex of
the upper part of the cerebral convolutions, less so at the lower end of the F. of
Rolando, but could be traced as far as the left anterior calcarine region. No
proliferation could be distinguished in sections from any portion of the right
hemisphere. Scattered throughout the sections of all portions of the cortt'x of the

250

AKCHIVES

left hemisphere, but most marked at the periphery of the cortex of the Island of
lieil were curious bodies which when small appeared within the protoplasm of glia
cells and when large were lying free in the cortex. The smaller bodies were homo¬
geneous, almost hyaline, and stained pale blue with the I. G. stain, and pink with
Van Gieson’s solution. The larger bodies stained pink at the periphery, and
diffusely blue or violet internally with a double stain. Heidenhain’s hsemotoxyln
stained the centre a brownish black in some cases. These bodies gave the violet blue
reaction of chi tin when treated with iodine solution and zinc chloride and stained
green by Bethe’s method of staining chi tin. They were dissolved by strong acids
and acidified chloroform, leaving spaces in the tissue. The membranes over the
growth showed fibrous thickening, endothelial cell proliferation, and marked small
round cell infiltration around some of the vessels. In pieces of membrane taken from
the central and occipital regions of the right hemisphere there was also a marked
small round cell infiltration in some parts, but the membrane was not much
thickened.

t 'f/sc 2.— Sinnll nmnd ('ell Surroina of fJte frnntnl loho of ihr right i 'trehntl llvniii<p]n>rc.

J. L., aged 45, had a history of intemperance, sleepiness and dulness. He was
depressed, demented, blind and tremulous. Knee jerks very brisk. Death occurrcMl
two months after admission from atomy and distension of the bowel.

At the post-morti tn examination there was found to be a general distension of
the gut, especially marked in the large intestine without any sign of obstruction
(? paralytic). On removing the calvarium there was seen to be some excess of
cerebrospinal fluid, and, much thickening and congestion of the pia arachnoid mem¬
brane. In the right hemisphere a large mass of new growth occupied the prefrontal
region and extended into the inferior frontal convolution, where it presented a
fungating appearance with pigmented areas. On section of the hemisphere the growtli
was seen to extend backwards as far as the middle of the lateral ventricle, but pos¬
teriorly only involved the white matter; at the level of the internal capsule there
had been a definite hcemorrhage.

Microscopical examination of the growth showed small round cells, uniform in
size, and staining reaction, which were divided in places by thin strands of fibrous
tissue. There were numerous imperfectly formed blood vessels and evidence of
hfemorrliage in the form of red cells and clot. At the margin of the growth areas
of proliferating neuroglia cells were seen with branching processes, and there was
well-marked proliferation of the endothelial cells lining the perivascular lymphatics.

The nerve cells of the cortex showed some disorganisation well beyond the edge
of the growth. Chromatolysis and eccentricity of the nucleus were present in the
central region, but the changes became less marked the farther the sections were
taken from the vicinity of the growth, those from the parietal region being very
little removed from the normal. Some of the vessels showed groups of lymphocytes
around the walls, and the^se cells were also scattered throughout the w’hite matter
n(*ar to the growth. There was some proliferation of the perivascular endothelium
in the cortex of the central region and numerous plasma cells were seen. In pieces
of membrane taken from over the region of the growth there was patchy thickening
duo to overgrowth of the cells of the endothelial lining. Many of the vessels were
surrounded by a well marked small round cell infiltration. In the membrane from
the occipital region similar changes were present, but in a much smaller degree.

NOTES ON FORTY NEW GROWTHS

251

(June o.—Gliomti of the frontal lolte of the Uft Cerehral Jleminphere,

E. H., aged 45, had been weak-minded from childhood.

There was a history of fits and strangeness of manner for six months. He was
dull, slow, srtupid, and of faulty habits, had glycosuria, and died comatose.

At the 'post-mortem examination a large soft tumour occupied the left frontal
region. It caused bulging of the lateral surface, and on the mesial surface had
obviously pressed on the opposite hemisphere. The tumour extended through the
left optic thalamus and pons, and in these rf'gions contained hemorrhages. The
cortex over the tumour areas was pale, and the striation indistinct. Films made
from the growth, fixed by exposure to thorium nitrate and stained by the I. G.
method, showed elongated cells with large nuclei and often branching processes.
Scattered among these were irregularly round cells with dark nuclei and protoplasm
staining a clear pink. These cells had generally rather a large amount of proto¬
plasm in proportion to the size of the nucleus and did not resemble either the
plasma cells or neuroglia cells in size, shape or colouring. Sections of the growth
showed a uniform structure of ncuiroglial tissue. It was most cellular around the
vessels, where there was often alsc an overgrowth of true fibrous tissue. There were
immerous degenerated areas, mostly small, and at the edges of these and scattered
throughout the tissue were numerous pink cells with dark nuclei. In some cases
these pink cells were seen surrounding the vessels and replacing the neuroglial cells.
The way in which this growth infiltrates the nervous tissue around, and the apparent
method of extension by multiplication of the existing neuroglial cells some distance
beyond the obvious edge of the tumour, resembles that described in Case 1. The
membranes also were affected in a similar fashion to the other case, but the
membrane over the lateral surface of the hemisphere in this case showed more small
round cell infiltration around the vessel than was seen in any other case so far aw\ay
from the centre of the growth.

Cane 4.— Glioma of the ritjht 'Vemporal Lohe.

B. B., aged 67, had a history of having had a fit, but was only under supervision
for one week. Death occurred from pjieumonia with terminal gangrene.

At the post mortem there was seen to be a slight thickening of the pia mater and
slight excess of cerebrospinal fl^uid. On dividing the cerebral hemispheres a circular,
dark red, hcemorrhagic mass w^as seen (about 2 cm. in diameter) at about the centre
of the right hippocampal gyrus. The w'hole of this gyrus and the adjacent temporal
convolutions were abnormally soft to the touch, had some obliti^ration of their secondary
sulci, and on section showed lueinorrhagic points. The difforentiation of grey from
white matter was not clear and the circular hsemorrhagic area only extended for
about 5 mm. below the surface. Films of this region showed uniform glia cells with
well-marked branching processes and numerous blood vessels. Sections of tissue
taken from the same part showed distended, imperfectly formed vessels with
numerous haemorrhages. There was marked enlargement and proliferation of
the endothelial cells and some lymphocytic infiltration in the vessels and
tissues around. Some multi-nucleated cells were seen in the h«emorrhagic
areas. The substance of the tumour consisted of a uniform growth of neuroglia cells
with oval nuclei and branching processes, and the structure approached a cellular
rather than a fibrous glioma. Very few nerve cells could be seen in the cortex over
the growth and most of those present were in process of disintegration. Sections

252

ARCHIVES

taken from the anterior end of the hippocampal gyrus showed also a uniform
structure of glia cells with well-marked perivascular lymphocytic infiltration, which
extended some distance into the tissues around the vessels and was not confined to
the perivascular lymphatics. Many of the glia cells in this case contained hyaline
bodies similar to those described in Case 1. They could be seen in the substance of
the glia cells as small, round, almost transparent globules, and all sizes could be
traced to the larger free bodies taking an acid stain at the periphery and basic in
the centre. In some cases the rim of the latter appeared to be separated from the
centre and had a lobulated, mulberry-like appearance. The membranes over the
growth showed an increase of endothelial cells and a lymphocytic inhltration around
the vessels. In the membranes from other regions there was a general thickening
and increase of eiidotlielial cells, but much less lymphocytic infiltration around the
vessels.

rVfsc 5 .—Glioma of left Frontal Lobe.

G. C., aged 64 years, commenced to have epileptic fits 12 years before admission,
and these had continued with varying intensity ever since. On admission the speech
was coherent, and the attention easily obtained and retained, and the patient was
clean, decent and quiet. The memory was bad, the patient was dull and depressed,
and had both illusions and delusions. Hearing was defective, and two months
before death there began to be some difficulty in speaking. Death in status
epilepticus.

At the post-mortem examination there was seen to be a tumour of the left frontal
lobe of the brain, beginning about 1*5 cm. from the anterior pole of the hemisphere
and extending backwards about 6 cm. ; in width the tumour area measured 4’5 cm.
The colour of the growth was a pinkish grey, and the change to normal tissue on
the anterior and inner surfaces was imperceptible, but on the lateral surface (Island
of Reil) there was a distinct line of demarcation apparently fibrous in nature,
limiting the growth. Microscopical sections of the growth showed a uniform over¬
growth of glial tissue with strands of cells running through it in places. These
cells were for the most part oval or round, and mononuclear, and had no definite
relation to vessels. All stages could be seen from round cells to typical branched
neuroglial cells. Sections taken from the cortex beyond the part affected by the
tumour to the naked eye showed a great increase of glial nuclei, decreasing in degree
as the tissue was farther removed from the growth, suggesting rather that the over¬
growth of glia was due to a chronic proliferative influence spreading over the region,
than that it was a localised growth extending into the brain tissue.

The nerve cells showed deviation from their normal character in proportion to
their iniplication in the growth. The remains of a few were found within the
gnjwth, at the edge they appeared in various stages of disintegration, and in many
cases were soen as mere uniformly staining, elongated masses of protoplasm.

The vessels of the cortex showed an undoubted proliferation of endo- and peri¬
thelium, but not to a very marked extent.

The membranes over the growth showed a patchy endothelial proliferation, and
in some places a moderate degre<^ of infiltration around the vessels. In the mem¬
branes over the occinital region th(^e changes were also present, but less marked
than in the membrane near the growth.

NOTES ON FORTY NEW GROWTHS

25a

CV^s(? 6 .—AdeunnuL of ths Fineal GUind.

J. W., aged 48. On. admission was dull^ stuporose, incoherent, and depressed.

The motor power was impaired in both legs and the right arm, and the patient
was unable to stand alone. The speech was thick and slurred, the knee jerks
brisk; there was no ankle clonus and no nystagmus or ptosis. The pupils were
equal, regular, and reacted to accommodation, although there was marked optic
neuritis. In the asylum the patient had frequent attacks of tachycardia without
discernible cause. Between the attacks she was either stuporose or restless and
excited.

At the post-nwrlem examination a tumour was found bulguig into the Circle of
Willis; it was whitish grey in colour, and about the size of a small tangerine
orange, measuring 5 cm. by 4 cm. by 3 cm. It had a deiinite adherent, fibrous
capsule, and was shelled out easily and completely. On section it showed numerous
cystic spaces, some empty, others filled with gelatinous material. The tissue was
in some parts cartilaginous, in others soft, and contained gritty particles.

Microscopical examination showed that the tumour was composed of epithelial
tissue surrounding spaces filled, in some cases with homogenous material, in others
with myxomatous tissue. At the edge of the spdco the epithelium was columnar
and stained deeply; below this columnar layer the cells were oval or cuboid in
shape, and stained badly. Some cells contained several nuclei, and these were poor
in chromatin. In places the cellular tissue was invaded by mononuclear cells and
some multinucleated cells were seen. The homogeneous material seen within tne
spaces in some cases took the basic, in others the acid dye. The spaces filled with
myxomatous cells showed a hyaline matrix in some parts, and here the tissue was
extremely vascular and small hiemorrhages had evidently occurred. There was
some true formation of cartilage which in parts had been infiltrated with calcareous
salts. In the myxomatous tissue of one part large cells resembling the nervous
elements of the retina were seen.

Scattered about the section, but most noticeable in the interepithelial spaces,
are cells with a dark round nucleus, about the size of that of a lymphocyte, but oft<*n
having a considerable amount of protoplasm. The protoplasm differs from that of
the lymphocyte in staining pink, and having, in the larger cells, a granular appear¬
ance due to eosinophil granules. The membranes over the growth and away from
it show'ed some general thickening, and infiltration of the vessels with lymphocytes
was seen in the former position. There were numerous concentric hyaline bodies
scattered over the surface of the membrane in all parts.

Case 7.— Adenoma of the J/ituitary Body.

H. R. H., aged 44. Had a history of a fall from a cart with injury to the head
12 months earlier, since when patient had complained of failing eyesight. He had
been peculiar for six months, having frequent delirious attacks accompanied by
nausea and retching. He was in Guy’s Hospital before being admitted to the
asylum, and their notes state that there was no papillitis (field of vision not
mentioned). The reflexes were not exaggerated, lumbar puncture showed nothing
abnormal, and there was no tenderness of the head.

On admission to the asylum he was confused and stupid, and often incoherent
in his speech. He had coarse treimus, inco-ordinalion of upper and lower extnuiii-
ties, and unsteady gait. The knee jerks were brisk, but there was no ankle clonus.

254

AJlCHIVES

A history of syphilis was obtained. After admission the muscular power remained
good, but patient had a seizure followed by left-sided convalsious, loss of con¬
sciousness, collapse and death.

At the post-mortem examination the convolutions of the brain were found to be
flattened, and a tumour about the size of a chestnut was seen in the region of the
pituitary body. Both lobes of the pituitary were enlarged, the glandular portion
more so than the nervous. The latter was pale in colour, but the glandular por¬
tion was a deep maroon colour, and of about the consistency of natural liver sub
stance. The thyroid gland was natural, and there were some remains of the
thymus gland present. Other pathological conditions were old perihepatitis and
cystic kidney.

Examination of microscopical sections of the tumour showed a uniform growth
of small cells with darkly staining round or oval nuclei and protoplasm, varying
considerably in amount, but always staining a clear pink colour with the I. G.
stain. The glandular portion of the tumour was extremely vascular, large and
small vessels abounding in all parts, and there was evidence of diapedesis and
small haemorrhages in places. No lymphocytic iniiltration was seen; the nervous
portion of the pituitary body, although white in colour to the naked eye, yet
showed microscopically a growth of similar cells to those of the vascular portion.
The vessels were much fewer in number, and the cells less distinct from one
another.

In well-stained specimens of the I. G. method, many small cells varying from 1 /li
upwards were seen, but most of them were very minute. The membranes over the
tumour showed an infiltration with tumour cells, but no obvious small round cell
infiltration. Over the vertex in the ascending frontal regions, the membrane showed
a slight lymphocytic infiltration around some of the vessels and small groups
(about six or eight) of tumour cells clumped together.

t 'a.sc H.— (Jlun'uidal cell c/nni'th iii 4/// Ventrirlc.

E. VV., aged 31 yeai*s. Was transferred to the asylum from the union as a case
of puerT>eral mania.

There was a history of the birth of a living child five weeks before admission,
after three pivguancies resulting in miscarriage or still birth. The patient had
complained of great thirst three weeks before admission, was always drinking,
and was greatly emaciated. In the Infirmary she failed to recognise her friends, was
excited, noisy and restless, and had hallucinations. Later she became depressed,
but was always ravenously hungry and thirsty. On admission to the asylum there
was air hunger, but no physical signs in the chest. The urine had a Sp. Gr. of
1042 and sugar was present in large quantities. Tho patient was dull and
unable to give any account of hcu'self. The pulse was rapid and feeble. Tempera¬
ture 06. Patient vomited twice on November 6th, became comatose, and died on
November 7th, two days after admission.

At the post-mortem examination the pam^reas appeared normal. There was
chronic tliickt ning of the pleurie and some dilation of the right side of the heart.
On removing the calvarium there was a slight excess of cerebrospinal fluid and the
surface of the brain appeared normal.

Bulging into the calamus scriptorius of tho fourth ventricle was a small firm
tumour about the size of a i>oa.

NOTES ON FORTY NEW GROWTHS

2o5

Microscopical sections of the growth showed a small area of choroidal epitheJium,
surrounded by a comparatively deep and well-marked margin of fibro-neuroglial
tissue. It was the latter which had invaded the substance of the medulla and
caused pressure on the nuclei in the region of the calamus. The vessels in the
medulla were dilated and in some cases surrounded by lymphocytes.

Sections of the cortex taken from the motor region showed a slight but un¬
doubted infiltration of small round cells in the neighbourhood of the vessels. The
nerve cells showed disorganisation, chromatolysis, eccentricity of the nucleus, and
an irregular disposition of the cells with regard to the cortical surface. Some
phagocytosis was apparent, but the cortex was markedly infiltrated with adventitial
cells.

The membranes showed a patchy increase of small round cells about the vessels,
more marked in some parts than others, but not confined to the occipital region
of the growth.

Case 9 .—EndoihvliiHnu of the riyht fnoitdl lohe.

J. C. A stonemason; was admitted to Charing Cross Hospital complaining ol
headaches for a year (continuous during the past two months), nausea, fits, and
loss of power over the legs. Just before admission he began to have incontinence
of urine and feeces.

He suffered from complete loss of memory, always complaincKi of feeling cold,
was always sleepy, and generally appeared to be crying. There was well-marked
optic neuritis in both eyes. After admission liis temperature rose to 103*2° F. He
had two fits, and later lost the power in his trunk muscles, and had to be lifted
in and out of bed.

At the post-mortem examination the right hemisphere was found to contain a
tumour about the size of a pigeon’s egg in the frontal lobe. It only appeared on the
surface at one point. The substance of the tumour was firm and vascular, pinkish
grey in colour with irregular streaks of yellowish matter suggesting a “regressive
metamorphosis.” There was an area of softening around the tumour. Both ven¬
tricles contained blood-stained fiuid, and there was a Inemorrhagic area in the
posterior part of the pons.

Microscopical examination of the growth showed cells of tw'o types. 1. Large
epithelial cell, columnar or cuboid in shape, at places arranged in alveoli, and
divided by broad areas of fibrous tissue. 2. Smaller cells with a clearer protoplasm
staining more pink than violet by the T.G. method, and having dark nuclei ; these
occurred in patches or elongated strands, and in some cases were seen as circular
inclusions within the protoplasm of the larger cells. These small cells show a
greater tendency than the large ones to a regressive metamorphosis. In some places
the strands formed by them had completely degenerated and appeared almost
structureless. In other places complete strands show healthy cells, but of quite a
different character from the large epithelial type.

There was some overgrowrbh of fibrous tissue around the vessels, and a lymphocytic
reaction around the vessels at the edge of the growth. The brain substance beyond the
limits of the growth was infiltrated for some little distance with multinucleated cells.
The membranes in this case showed a woll-marktd small cell infiltration around the
vessels, but there was no general thickening of the membrane, and no obvious
endothelial proliferation.

256

Case 10 .—Midiiple secondary Carrmamaious yroivth of both hemispheres.

A. L., aged 60 years, had the left breast removed for cancer about six months
before admission to the Asylum. On admission there was recurrence in the scar and
surrounding skin, and enlarged glands in the left axiUa.

At the post-mortem examination the axillary and supraclavicular glands were
found to be enlarged and hard, and some of the mesenteric glands were also affected,
but no malignant disease was found in the mediastinal glands nor in any of the
abdominal or thoracic organs. An enlarged mass of glands surrounded the carotid
sheath on the left side. On removing the calvarium the dura was pale, but not
adherent The convolutions of the brain were largely obliterated, and the pia was
adherent to the cortex in many places. Multiple areas of new growths were found
in both hemispheres, involving all the lobes. The Sylvian fissure could not be
opened without tearing the substance of the brain, on account of multiple growths
along the course of branches of the middle meningeal vessels. On microscopical
examination the growth was seen to consist of irregularly spheroidal cells arranged
in columns or groups, often incompletely separated one from the other. Strands of
fibrous tissue occurred varying very much in amount in different sections. The
nuclei of the cancer cells stained faintly in the majority of cases, and the proto¬
plasm was often vacuolated and contained inclusions in many parts. Numerous
definite atypical pink cells with dark nuclei were seen free, both among the
cancer cells and in the nerve substance beyond the edge of the growth. Many of
the cancer cells contained myelin debris within their protoplasm. Sections of the
glands showed a similar structure, but fewer inclusions were seen, and the cancer
cells had a tendency to be more cubical and better formed than in the cortex.

Some of the vessels of the cortex in the neighbourhood of the growth were infil¬
trated with round cells (Plate I., Fig. 1), and others were surrounded by single or
double layers of cancer cells which were obviously spreading along the perivascular
lymphatics.

The membranes in the parts examined showed some slight thickening and a
patchy infiltration with lymphocytes around the vessels over the area of the growth.
These changes were less marked than in some of the gliomatous tumors.

Case 11 .—Multiple secondary Sarcinnahms Groicths in hoik hemispheres.

H. J., aged 53, was stupid, but able to converse rationally until one month
before death. She then became resistive, troublesome, and very restless. Jactatory
movements of the arms appeared, with exaggerated tendon reflexes, and Babinski’s
sign was present on the right side. Death ensued from progressive asthenia.

At the posi-moriem examination a mass of new growth was found at the root of
the right lung extending into all three lobes. Tlie bronchial glands were involved,
and there were multiple areas of new growth in the brain. These areas were
pinkish in colour, and in the centre contained clear gelatinous matter of a semi¬
fluid consistency.

Microscopic examination of sections of the tumour in the lung showed a cellular
growth, the cells for the most part being small and round, or oval with very little
intercellular fibrous tissue, but in some sections, both of lung and brain growths,
there were definite clumps of larger cells of the endothelial type, and all degrees
can be seen from these to the small round cells, although the latter predominate.
The pink bcnlies with dark nuclei in sections stained by the I.G. method are w=^ell

J^OTfeS ON ^RTY NEW GROWtHS

267

Seen as inclusions in some parts of tke sections, and numerous tiny cells having a
similar staining reaction are seen scattered among the small round cells of the
growth.

The membranes were not greatly thickened, but there was a well-marked
lymphocytic infiltration around some of the vessels.

rVise Vl.-^EndoiheJioma growlti(j from the Dura Mater.

E. T., aged 60 years, was depressed on admission, and had auditory hallucina¬
tions. The pupils wore unequal, but reacted to light and accoramodatioji. Death
occurred from cardiac failure after a collapsed condition lasting several d^ys.

At the post-mortem examination the lungs showed signs of broncho-pneumonia,
and there was gei>eraJised arterio-eclerosis.

In the parietal region of the left heonisphere attached to the durfk w,as a amall
circular circumscribed growth about the size of 9, small Spanish nut.

On microscopical examination the growth was seen to consist of elongated .and
spindle-shaped cells with round or oval deeply staining nuclei. There was some
slight round cell infiltration at the base, and the growth contained vessels with
well-formed walls. No inclusions or atypical pink cells were seen.

Case 13 .—Erulothelioymi groiring from the Dura Mater,

£. D., aged 63 years, had dysentery aiter adraii^sion, and died of acute bronchitis.

At the post-mortem examination evidence was found of broncho-pneumonia,
obsolesoent tubercle of the lung, senile arterio-sclerosis, atherpma of the valves, and
hypertrophy of the left side of the heart.

In the temporal region of the left hemisphere of the brain, apparently enclosed
between the layers of the dura mater, was a small tumour about 5 mm. in dia^neter,
definitely circumscribed, soft in consistency, and whitish in colour.

On microscopic examination the growth was seen to consist of insularly shaped
oells and multinucleated protoplasmic masses. The nuclei were mostly pale and
vacuolated. The growth was very vascular, the vessel walls ill-formed, and a
considerable number of red corpuscles were lying free in the tumour. Xhare was a
diffuse lymphocytic indadtration and some strands of fibrous tissue. The tumour was
growing from and spreading along the inner surface of the dura. No inclusions
or free atypical pink oells were seen.

Case 14 .—Endothelioma groiring from the Dura Mater.

M. A. S., aged 74 yeaiSi was stated to have had fits, but number aud tipie were
not given. She died of bronchitis.

At the post-moriem examination a small nodular growth was found in the .right
parietal region near the longitudinal sinus. It was about the size of a Spanish
nut, and soft and friable to the touch.

Microscopical sections of the growth showed elongated spindle-shaped cells with
oval nuclei and irregular protoplasnuc masses containing several nuclei. The
growth was vascular with free red corpuscles scattered through the substance.

The tumour appeared to arise from the endothelium lining the dui^a mater; and
was quite localised

R

258

ARCHIVES

Case 15 .—Multiple gumniaia of brain and spinal cord.

E. D.y aged 44 years. Suffered from insanity with gross brain lesion. Her
speech was typically paretic, she had right facial paralysis and spasticity of the
right arm and leg with Babinski’s sign on the same side. Her right pupil was
the larger, and both were sluggish to light: she had grandiose delusions and feeble
health generally. She was collapsed for three days before death, and had consider¬
able difficulty in swallowing.

Posi-mortem Notes (from Horton Asylum).—The pupils were equal. The dura
mater thickened and adherent to the pia at the base. There was excess of cerebro¬
spinal fluid. The pia was irregularly thickened, and there were numerous spindle-
shaped thickenings at the branches of the vessels. The ventricles were dilated
and granular. Attached to the membranes on the roof of the 4th ventricle and
spreading over the right superior peduncle of the cerebellum was a small tumour,
larger than a pea, and not so large as a Albert. It was uniformly yellow in colour,
of the consistency of firm fat, and appeared to be attached to the pia. There was
some general atheroma of the vessels, evidence of an old perihepatitis, and the
capsules of the kidney were thick and adherent. The tumour on the right superior
cerebellar peduncle was yellow in colour, measured 1 cm. by 6 cm. in diameter, and
extended down into the substance of the medulla. On the spinal cord were numerous
small hard white nodules. At the level of the 7th cervical segment was a small
growth involving the poster!o-lateral region on the right side ; in the cervical and
dorsal regions were various nodules on the posterior roots, and in the dorsal region
a few nodules in the substance of the dura.

Microscopical sections of the tumour on the superior cerebellar peduncle showed a
uniform growth of fat cells and fibrous tissue. The former was most abundant at
the free edge of the tumour, while the fibrous tissue formed the base, and infiltrated
the medulla beneath.

The nodules on the coixi were uniformly cellular growths of a gummatous nature,
and there was a very marked small round cell infiltration round the vessels in the
neighbourhood, and also of the pia mater in all regions. No cell inclusions were
seen in any of the sections and no cells taking the typical pink colour with the I.G.
method, although the tissue was breaking down in some parts. Some scattered cells
with dark crimson eosinophil granules were present in the gummatous areas.

The cortical cells of the motor region showed a curious vacuolation of their
protoplasm. On staining with Scharlach s stain and Sudan III. these cells wei’e
seen to contain granules which took the characteristic deep red reaction given by
fat.

The cortical vessels showed obliterative endarteritis and some periarteritis.

Sections through the medulla at the level of the 9th nucleus showed: —

1. Cell infiltration of the floor of the medulla with curious excrescences consisting
of glial cells and fibrous tissue.

2. Cell infiltration around the vessels and in the pia with some new formation of
fibrous tissue.

3. In the region of the 9th nucleus two small areas of hiemorrhage.

4. Chromalolysis and degeneration of many of the nerve cells of the nuclei.

The membranes of the brain showed a considerable degree of endothelial pro¬
liferation ; it w'as not more marked around the vessels and no small round cell
infiltration was seen in membrane removed either fnDm the medulla and cerebellum
or the vertex.

N’OTKS ON t’OEtY NEW GROWTHS

259

There was, however, a very noticeable lymphocytic reaction in some parts of the
membrane of the spinal cord.

Cane 16 .—Fatty tainoiir at the posterior border of the spleninmy incolring the

fibres of Lancisi,

A. B., aged 41 years, suffered from chronic dementia and died with symptoms of
broncho-pneumonia after developing gangrene of both feet, accompanied by purpura
of both legs.

At the post-mortem examination all the convolutions of the brain were found to
be wasted except those of the occipital lobe. There was a small yellowish tumor
lying between the hemispheres at the posterior end of the corpus callosum. The
ventricles were dilated and granular. On examination, after hardening, the fibres
of Lancisi lying on the upper surface of the corpus callosum appeared to become
gradually thicker as they proceeded backwards. At the posterior border of the
splenium they became continuous with a small yellowish nodule 1 cm. in diameter,
which was attached to the callosal fibres, but did not appear to infiltrate below the
surface.

Microscopical examination showed that this small tumour consisted of a uniform
growth of fat cells with very little fibrous tissue ; it was quite superficial, and did
not infiltrate the corpus callosum.

The membranes were very little affected. There was some general chronic
thickening and practically no infiltration of the vessels with small round cells.

Case 17 .—ixumma of Left frontal hemisphere.

E. F., aged 34 years. Had a typical history of syphilis with a premature
climacteric six years before admission. There had t>een gonorrhoea two years, and
pneumonia and pleurisy one month before admission. After the latter illness fits
commenced and increased in number until before death she was having three or
four every day.

At the post-mortem examination the dura mater was thick and adherent over
the frontal region of the left hemisphere, and on section a gumma was found
spreading into the hemisphere from the surface. There was also a gumma involving
the whole of the superior and middle convolutions of the right hemisphere, and
extending backwards as far as the ascending frontal convolution, but apparently not
involving it. The gummata were indurated outside and caseous internally. On the
right side there were no adhesions to the dura.

There were multiple heemorrhages in the pons and medulla. The vessels in the
Sylvian fissure on section showed crescentic, endothelial thickenings. Other patho¬
logical conditions found were evidence of old perihepatitis and some atheroma of the
aorta. .

On microscopic examination sections from the centre of the mass showed
structureless material with debris of cells and nuclei. At the edges of the growth
there was lymphocytic infiltration, and in some parts formation of true fibrous
tissue. There was new formation of vessels at the limits of the growth, and
dilation of perivascular lymphatics without much endothelial proliferation.

Strands of fibrous tissue, carrying newly-formed vessels, ran into the substance
of the brain tissue, and the capillaries in the neighbourhood were dilated. At the
growing edge of the tumour, spreading into the brain substance, were large round

X 2

2G0

ABCHIVES

raononuci’eBr dells of the variety usaally seen in syphilitic lesions of the brain
They have a relatively small nucleus (about the size of that of an ordinary lym¬
phocyte) but protoplasm, measuring often 30 to 40 p in diameter.

The membranes in this case showed a very dense infiltration with lymphocytes
over the growth and some proliferation of endothelium, the change being an acute
one, as the membrane Was not much thickened. In the portion of membrane taken
from the occipital pole, there was a slight general overgrowth of endothelial cells,
but no marked infiltration around the vessels.

CaHe 18 .—Ctutenfing Tuherchs of Cerebellum mid left frontal.

H. T., aged 6^ years, was admitted to the Great Ormond Street Hospital on
July 7th, 1907, and died on August 25th. There was a history of frontal headache,

and pins and needles in the limbs for the past four weeks, irregular vomiting for

seven days, and diplopia for four days before admission. The child had had
abscesses on face, chest, and thigh during the previous three months, which were
thought to be tubercular.

On admission the temperature was normal, the pulse 100 and irregular. The
mental state was normal, pupils equal, and active. There was no paresis of

muscles, but Konig’s sign was present. The knee jerks and plantar response

sluggish. There was double optic neuritis. After admission the patient developed
some right facial paralysis, and weakness of right arm and leg. The right cerebral
hemisphere was exposed and the brain explored, but no tumour was found. After
the operation, the child developed right-sided convulsions, and a fortnight later the
left hemisphere was exposed, and a nodular growth felt anterior to the Fissure of
Holando, but no attempt was made to remove it. The child died one hour later.

At the post-mortem examination, generalised tuberculosis was found involving
hmgs, pleura, spleen, liver and kidneys, and the cervdcal bronchial and mesenteric
glands. There was no ulceration of the intestines.

The brain was well convoluted, and showed a large area of bulging in the inferior
parietal and superior temporal regions of the right hemisphere, and involving the
region surrounding the posterior third of the Sylvian fissure. The bulging area
was spongy to the touch, and the fissures of that part were shallower than those
ill other parts of the brain. On section a small pigmented spot was seen about
2*5 cm. below the posterior end of the Sylvian fissure, which suggested an area of
hternorrhagic encephalitis.

The left hemisphere showed a broadening of the upper part of the ascending
frontal convolution, and on cutting through this area, two hodnles of caseating
tul-ercle were seen, one just above the genu, the other about 1 cm. from the mesial
surface. In front a tubercular mass was seen to involve the whole of the white
matter of the superior frontal convolution, but did not affect the cortex. The
right cerebellar hemisphere was also the seat of a tuberctilar mass measuring 6 cm.
by 2 6 cm. by 3 cm. The dentate and roof nuclei were not involved.

Microscopical sections of the growth showed caseating nodules with typical giant
cells, epithelioid zone, and some patchy and diffuse lymphocytic infiltration which
extended into the cortex around, but was not extreme in degree in any part. The
endothelial lining of the capillaries showed slight proliferation, and the vessels in
the membranes dipping into the fissures also showed this change, as well as some
diffuse lymphocytic infiltration.

NOTES ON FOBTY NEW GROWTHS

261

The medallary portion of the section of growth from the right hemisphere
showed numerous small areas of encephalitis, lliese consisted of small patches of
serous exudate surrounding vessels, with a smaller zone (immediately around the
vessel), of cellular infiltration. The cells here, as has been noted by Oppenheim in
similar acute cases, consist of mononuclear cells only, no polynuclear cells being seen.

The membranes over the tubercular area in the left hemisphere showed small,
thick clusters of small round cells not always near vessels. There were an abnormal
number of lymphocytes scattered over the membranes, but they had no especial
relations to the vessels.

In the portion of membrane examined from an apparently unaffected part of the
brain none of the above clusters of lymphocytes were seen, but there was some
general increase in the number of lymphocytes present.

Case X^.—Enreplialoid Caneer of the uiper lobe of the left lung.

J. C., aged 71 years, suffered from bronchitis on admission to the Asylum, and
died suddenly four days later.

At the post-mortem examination an ulcer was found in the duodenum about one
inch from the pylorus. The ulcer was about 1 cm. in diameter, with clean-cut,
slightly overhanging edges, and was somewhat adematous, but not indurated. The
floor was composed of muscle substance. The pancreas was not infiltrated, there
were no adhesions, and no naked-eye evidence of malignancy.

In the centre of the upper lobe of the left lung was a whitish mass, which had
every appearance of being a malignant growth—it was soft, whitish yellow, and had
a well-defined edge.

Microscopical examination of sections of the duodenal ulcer showed no infiltration
of the muscle wall with epithelial cells, and no obvious signs of malignancy.

The growth in the lung consisted of areas of epithelial cells, oval, cuboid, or
columnar in shape, staining violet by the I.G. method. In the centre of these areas
of epithelial cells were well-formed pink bodies of all sizes and shapes, often
containing dark nuclei. Smaller bodies of this tyx>e also occurred as inclusions
within the epithelial cells, and some were seen free in the lymphatic channels around
the bronchi. They varied in size from 1 ^ to 25 M in diameter.

At the outer edge of the epithelial cell groups there was in some parts a well-
marked small round cell infiltration. The lymphocytes in this infiltration differed
very materially in size, shape and jftaining reaction from the pink staining bodies
in the centre of the epithelial groups.

Cnse 20 .—Scirrhns Carchuyma of the pyloric end of the Stonuich, and Fibroma
over the left internal auditory meatus.

R. T., aged 77, suffered from senile dementia and had presystolic and systolic
cardiac murmurs. Three months after admission to Claybury Asylum she began to
have Gsdema of the feet, and died suddenly 11 months later.

At the post-mortem examination the pyloric end of the stomach showed a diffuse
thickening of the wall, which had the effect of narrowing the pyloric orifice. The
mucous membrane was thickened and showed areas of patchy congestion. The
pancreas was large, and had a swollen and inflamed appearance.

On removing the brain a small rounded tumour, soft and about the size of a
Spanish nut, was found, lying over the orifice of the left internal auditory meatus.

262

AECHIVES

It was not attached to the brain, but rested on the under surface of the cerebellum
and although it lay beside the facial nerve was not connected with it.

Microscopical examination.—The sections from the pyloric end of the stomach
showed a well-marked lymphocytic infiltration around the vessels, but no definite
malignant growth was seen.

The section of the pancreas contained a small lymphatic gland which was
attached to it, and lying between the fibrous tissue strands of the capsule were
definite large epithelial cells, either singly or in groups of two or three. They had
the characters of the cells of scirrhus carcinoma, and there was nothing to suggest
that there had been suflScient inflammatory reaction to cut off pancreatic cells from
the gland. In the lymphatic gland itself there were numerous elongated bodies
staining almost black, which appeared to be some form of saccharomyces.

The liver showed some areas of badly staining tissue, and there was a marked
small round cell infiltration around some of the larger vessels, with irregular strands
of fibrous tissue running between the cells.

The section of the spleen appeared natural.

The growth at the base of the brain proved to be a cellular fibroma containing
areas of vascular tissue surrounded by very poorly developed walls, the margin of
the bleed space being in some parts lined with fibrous cells only. There was some
pigment in these sections.

Case 21 .—Cancer of ike iSUmmck.

F. G., aged 83 years, became emaciated, w^ak, and died of exhaustion after a
fit. She had no symptoms of carcinoma of the stomach.

At the post-mortem examination a large fungating mass was found at the
oesophageal end of the lesser curvature of the stomach. It extended through the
stomach wall and caused adhesion to the left lobe of the liver behind, and there was
considerable contraction of the wall of the stomach. There ax^peared to be no
obstruction to the oesophageal opening, nor did the growth involve the oesophagus
in any way, but nodules of growth were found in the pancreas, mesentery,
mediastinal, and cervical glands.

Microscopical examination of the growth showed groups of cuboid and columnar
cells separated by fibrous strands. The growth invaded the muscle tissue, and
spread under the cardio-oesophageal junction, but did not involve the surface
epithelium of the oesophagus.

Clear pink cells, often containing bi-partite nuclei, appeared in groups within
the cancer cell areas, and were also seen in groups in tlie muscle tissue without
being surrounded by cancer cells.

The secondary growths were of similar structure to the primary, with large areas
of clear cells. The latter were numerous in the lymph channels, and in some parts
of the kidney they were invading the substance without any cancer-cell intervention,
sending up processes of growth and also scattered throughout the kidney substance,
but the kidney cells did not appear to have become cancerous. They were
degenerating, but not quickly dividing. The tissue showed very little sign of
pressure from the growth. Some of the epithelial cells of the kidney were lying
loose between the small infiltrating cells, and in some places the small cells appeared
within the epithelial cells at the edges of the growth.

NOTES ON FORTY NEW GROWTHS

Case 22 .—Cancer of the Stomach,

A. S., aged 69 years, died of progressive asthenia. A few days befoire death there
was distention of the upper part of the abdomen and oedema of the feet. At no time
was there either vomiting or constipation.

At the post-mortem examination an area of new growth, about 3*5 cm. in
diameter, was found at the oesophageal end of the stomach, and there were several
small polypoid growths near the pylorus. The whole of the liver was studded with
secondary nodules, the lungs were infiltrated with new growth, and the omentum,
kidneys, mesenteric, mediastinal, and cervical glands were also involved.

Microscopical sections of the ston'»ach growth showed a papillomatous mass of
columnar epithelium. The epithelial cells were often several layers in thickness,
and also formed groups. The lymphatic channels were crowded with lymphocytes.
Cells staining pink with the I.G. stain could be seen on the surface of th^ epithelium,
and as inclusions within the epithelial cells. The cancer growth was infiltrating
and breaking up the muscle substance. The growth in liver, lungs, and glands was
of the same nature as the primary focus. There were many inclusions to be seen,
and in the liver some heemorrhage had taken place. There was some small round
cell reaction and formation of fibrous tissue in parts. In films stained by I.G. after
fixation in alcohol the pink cells can be seen, although they are somewhat broken up.

Case 23 .—Cancer of the Stomach.

£. N., aged 63 years. No notes of this case were available.

The post-mortem notes were as follows:—On the posterior wall of the stomach
was a circular ulceration about 2 cm. in diameter, having a raised, thickened, and
infiltrated border. It was situated near the lef-ser curvature, about 2*5 cm. from
the pylorus. The mucous membrane over the ulcerated area did not appear to the
naked eye to be eroded except for a small area in the centre, but the surface was
somewhat blackened. Tlie liver was enormously enlarged, and most of the liver
substance was replaced by secondary new growths, whitish yellow in colour, and firm
except in the centre, where the growth was softer. The surface of the liver was
irregular and nodular, and many of the nodules were umbilicated.

The gall bladder was shrunken and contained no bile, but 708 small facetted
stones were found in it.

The pancreas was infiltrated with new growth, one nodule being the size of a
walnut. The lungs contained many small nodules and bronchial, mediastinal, and
mesenteric glands were involved.

Microscopical sections of the stomach showed irregular nodules of oval or cuboid
cells among the muscle substance. There was very little small round cell infill ration.
The growths in the liver, pancreas, and glands consisted of similar cells, with very
little fibrous tissue. In the centre of these areas of cancer cells in some cases were
cells staining pink with I.G. stain and having dark nuclei, and these cells were seen
as inclusions in the growths in glands, etc.

In the lung tissue there was an early pneumonic change, with a good deal of
fibrous exudation, some cellular proliferation and small-cell infiltration, and one or
two foci of growth.

264

ARCHIVES

Cowe 24 .—(Jancer of the Stomach,

A. L., aged 64, began to have frequent attacks of vomiting one month before
death, fof which no physical cause could be discovered. This condition was
progressive, and the patieiit lost weight, became very emaciated, and died of
exhaustion.

At the post-mortem examination a malignant growth was found encircling the
orifice of the oesophageal opening of the stomach. It spread for some distance along
the greater curvature of the stomach, and was soft and oedematous at the edges.
TTie stomach beyond the growth was small and contracted. There was no naked-eye
evidence of involvement of any other organ or glands.

Microscopical sections showed that the growth originated in the epithelium of the
stomach, the cesophageal epithelium being intact and apparently healthy, though
the growth was infiltrating for a very short distance below the stratified cell area.
The cells of the growth were cubical or oval in appearance, often vacuolated, and
with nuclei poor in chromatin, and strands of similar cells infiltrated the muscle
substance in all directions. The vessels in the underlying muscles were dilated,
and there was a very marked small round cell reaction to the growth, small islands
of tumour cells being surrounded by a dense wall of lymphocytes. Large areas of
mononuclear and multinuclear cells were seen. The former often occurred within
the protoplasm of the epithelial cells, the latter were free and formed large areas,
confined within a limiting boundary of epithelial cells, and also lying free in the
lumen of the superficial tubules. These cells had either clear or granular eosinophil
protoplasm and dark nuclei.

Vase 25 .—Carcinoma of Stomach.

F. W., aged 65 years, died with no other symptoms than those of progressive
asthenia.

The post-mortem examination revealed some degree of broncho-pneumonia and
general arterio-sclerosis. On the lesser curvature of the stomach there was a small
irregular lobulated growth, and beside this a second pedunculated one, each
measuring about 2 cm. in diameter. The mucous membrane was intact over both
growths. The stomach was not obviously thickened, but the whole of the stomach
was congested, and this condition was most marked around the pylorus.

Sections through the growth when examined microscopically showed a papil¬
lomatous structure, consisting of an overgrowth of the glandular epithelium lining
the stomach. The cells were for the most part only one layer in thickness, and
were arranged on each side of fibrous tracts, carrying vascular or lymphatic
channels. In one place the growth was infiltrating the muscle wall, and the strands
of muscle tissue were broken up and to be seen lying between the cancer cell groups.
There was a considerable amount of patchy lymphocytic infiltration, which in many
cases was definitely surrounding dilated vascular channels.

The lumen of the epithelial tubules contained many atypical pink cells with
dark nuclei, and similar cells could be seen in the lymph channels.

Another cell which appeared in large numbers in these sections was the swollen
lobulated cell with definite divisions of the protoplasm, which are seen in many
chronic inflammatory conditions.

NOTES ON FORTY NEW GROWTHS

265

Case 26 .—Carcinoma of Breast

£. L., aged 34 years, had the right breast removed for a hard mass felt in the
lower and outer quadrant of the gland.

Microscopical sections made from the growth showed groups of epithelial cells,
separated by thick bands of fibrous tissue, with a well-marked lymphocytic
infiltration in some parts. The growth was that of a typical scirrhus glandular
carcinoma mammae.

The cancer cells contained as inclusions some small masses of protoplasm, staining
a clear pink by the I.G. method, but very few of these masses contained nuclei.

Case 27 .—Carcincnna of the Breast

J. J., aged 80, collapsed suddenly while being forcibly fed during a period of
maniacal excitement.

Post-mortem examination revealed a very hard nodule in the right breast,
apparently a scirrhus carcinoma of very slow growth. The lungs and liver were
studded throughout with nodules of new growth, and the bronchial and mediastinal
glands were also affected. The thyroid gland was cystic and calcareous.

On microscopical examination the breast tumour was found to consist mainly of
dense fibrous strands. At one end of a section a few islands of cells were seen
scattered in the fibrous tissue. They were irregularly cuboid in shape, and occurred
in small groups. Cells with pink protoplasm and dark nuclei were relatively
numerous in this area. The liver showed areas of cancer tissue among the liver
cells as paler staining patches, these areas not being cut off from the liver substance
by fibrous tissue nor showing any evidence of round cell infiltration. The peri¬
vascular lymphatics of the portal system were infiltrated with the growth, and in
some places masses of cancer cells were seen growing along the inside of the portal
veins. There was some small round cell infiltration around the portal systems.
Typical pink cells of all sizes occun-ed as inclusions and free among the cancer and
liver cells. The cancer cells seemed not so much to be pressing on the liver tissue
as replacing it, and in some cases the advancing edge of the malignant mass was
formed of the clear cells with dark nuclei. The growths in the lungs showed similar
cell foi*mations, but the individual cells were larger. Several were joined together,
forming multinucleated masses, and were apparently more quickly growing.
Numerous inclusions were seen in these sections also.

Case 28 .—Carcinoma of the Breast.

A. B., aged 66 years, was suffering on admission from recurrent carcinoma
mammae. There was a sloughing growth in the right breast which involved the
skin, and the glands in both axillae were affected. The emaciation was extreme,
and death was due to exhaustion

At the post-mortem examination nothing further was found except a small
secondary nodule in the left kidney. There was no enlargement of mediastinal or
mesenteric glands.

The growth in the right breast on microscopical examination consisted of groups
and columns of cuboid or oval-shaped cells, divided by fibrous strands. There was
little small cell infiltration around the growth, but under the skin in sections taken
from that region the lymphocytic infiltration was quite massive. Tlie epithelial
cells of the skin contained as inclusions some of the bodies staining pink (with the
I.G. stain), and containing dark nuclei, and these were seen also in and among the
cancer cells. The growth was that of a typical scirrhus cancer of the breast.

266

ARCHIVES

Case 2P .—Ganrtr of the Brecisi.

E. S. P., aged 68 years, had no available history beyond that of an attack of
broncho-pneumonia.

At the post-mortem examination a hard nodule could be felt in tlie upper and
outer quadrant of the right breast, which on section was extremely tough and fibrous.

On microscopical examination the growth showed dense fibrous tissue with islands
of cells in small groups, and nodules separated by dense fibrous tissue. There was
no small round cell infiltration. None of the pink cells with dark nuclei were seen
in any of the sections, although many of the epithelial cells showed degenerative
changes.

( —Fibroma of Ufl ovary.

E. M., aged 33 years, suffered from puerperal mania. She had irregular pyrexia
cough, etc., and died of pulmonary tuberculosis.

At the Fost-murtem examination the left ovary wae found to contain a yellow
fibrous nodule, which on microscopic examination proved to be a fibroma.

The growth consisted chiefly of fibrous tissues, but there were many cellular areas
around the vessels, llie cells were chiefly connective tissne cells, but among them
were cells with a relatively large amount of protoplasm for the size of the nucleus.
This protoplasm was apparently breaking up into small greenish staining masses
(1. G. stain), and the cells appeared to be ovarian epithelial cells. There was a
well-marked infiltration with small round cells in some parts.

Case 31 .—Canicer of the Uterus.

E.P., aged 62 years, about a month before death complained of pain in the
back, and when exainine<l by the medical officer was found to have an enlarged and
tender uterus. The cervix was hard and puckered, and when the examining finger
was withdrawn, it was covered with blood. A slight foul, blood-«tained discharge
was noticeil afterwards, and the patient grew progressively weaker, but never
became emaciated.

At the post-moricm examination the alxlomen was distended, and about one to two
pints of clear straw-coloured fluid were removed from the abdominal cavity. The
whole of the great omentum and the serous surface of the large and small intestines
were covend wdth small white ncxiules, and the mesenteric glands were invaded by
a similar growth. Tlie serous surface lining the abdominal cavity was roughened
and congested. The liver was studded with several soft whitish nodules, and in one
case a hiemorrhage within a mnlule of growth.

I'he whole of the cervix and body of the uterus was replaced by malignant
growth, making the organ completely unrecognisable, and fixing it to the rectum and
bladder.

On microscopical examinatirm sections of the uterine growth showed muscle tissue
infiltrated with cells : some of the clusters were definitely composed of cervical
epithelium, but a myxomatous condition prevailed over large areas. There was some?
lymphocytic infiltration and fibrous tissue formation within the areas of growth, and
through the muscle substance, and some new growth of capillaries in the myxomatous
area.

The cancer cells w(*re oval, cubical, or spindle-shaped. Mitotic figures were seen
in many cells. Tlie small bodies with pink protoplasm and dark nuclei occurred as

NOTES OX FORTY NEW GROWTHS

267

inclusions and free among the cancer cells, and in some places formed multi-nucleated
masses. The secondary deposits showed a similar character to the primary, with
rather less lymphocytic reaction.

Ccise 32 .—Vapilloma of the Bladder.

J. C., aged 84 years, began to have retention of urine in December, 1907, and
later the urine contained pus. This condition persisted for some weeks, was followed
by incontinence, and the patient died on January 25th from broncho-pneumonia.

At the post-mortem examination the bladder was distended, the size of the cavity
larger than normal, and the walls thickened. It contained about three ounces of
pus. The prostrate was enlarged and contained a nodule, whitish in colour, about
the size of a walnut, which appeared to be neoplastic. There were no other signs of
new growth, and no glands appeared to be involved.

Microscopically the growth consisted of a groundwork of fibrous strands carrying
blood-vessels. On each side of these strands were layers of epithelial cells, varying
in depth and number. In some parts they formed large masses of typical cancerous
cells.

In the centre of many of the alveoli areas of cells were seen with dark nuclei
and a clear protoplasm, which stains yellow with Van Gieson’s stain and pink by the
I. G. method. The cells were irregularly columnar in shape near the vascular
strands, but more cuboid away from them ; they were often vacuolated and contained
many inclusions.

Case 33 —Bapillorna of the Bladder.

S. G., aged 61, had a lipoma of the shoulder and papilloma of the back. Ho
passed blood in the urine two days before death, but he had been treated for this
condition before being admitted to the asylum.

At the post-mortem examination the bladder contained about i ounce of pure
blood. Growing from the posterior wall were two large papillomatous masses which
occupied almost the whole of the interior of the bladder. They were attached to the
bladder wall by narrow peduncles, and there was no naked eye infiltration of the
muscle substance of the bladder, and no secondary deposits in any other organ.

On microscopical examination the growth was seen to be extremely vascular, con¬
taining vessels of all sizes, singly and in groups, and with walls varying in thickness
and often ill-developed ; in many places the walls consisted of a single layer of
fibrous tissue. The cells were uniformly spindle-shaped, and under the high power
could be seen to stretch aci\)ss the vessels in many places, in some of the vessels
there are many spindle-cells lying fiee in the lumen among the red cells and scattered
among them, both within and without the vessel are irregularly rounded bodies
having pink protoplasm and a small dark nucleus.

The growth was not infiltrating the muscle wall of the bladder in any of the
sections examined, but the mucous membrane was separat^'d from the underlying
tissue by a space containing mononucleated and multinucleated cells.

Case 34 .—Caurer if the Kidney.

H. D., aged 63, was emaciated, feeble, and subjeert to seizures, but had no
symptoms of kidney disease, and died from exhaustion.

At the post-mortem examination a large, whitish, irregularly-shaped mass was

268

ABGHIYSS

foand to involve the upper third of the left kidney. The left suprareiul body was
normal.

On microscopical examination the growth was found to be very vascular and to
be formed by epithelial cells interspersed with strands of fibrous tissue. Around
many of the small as well as the large vessels there was a well-marked small round
cell infiltration. The epithelial cells varied very much in size and shape, some being
cuboid, some around the vessels almost columnar, and many were vacuolated. They
tended to be aggregrated into small groups with fibrous strands separating one group
from another.

The type of growth was that described by Hektoen and Biesenan as hypernephroma
of the kidney. The adrenal body in this case was normal in size and also in naked
eye and miscroscopical appearance.

Case 35 .—Papilloma of the Bladder.

A. B., aged 46, a miller, began to have hsematuria in April, 1906. On examina¬
tion per rectum the prostrate was found to be enlarged, hard and tender. The urine
was acid and contained blood and pus. In June, 1906, he had lost weight, and had
periodical attacks of retention of urine. He became gradually weaker and more
emaciated, and died in October, 1906.

At the posUmortem examination the bladder was seen to be distended and filled
with thick yellowish blood-stained fluid. The mucous membrane was covered with
massive papillomatous excrescences, very soft, friable and villous-like ; the growth
covered the whole of the inner surface of the bladder except at the upper pole, where
the mucous membrane was thickened and sacculated. There was marked thickening
of the muscle walls of the bladder, but no obvious enlargement of glands in the
neighbourhood.

On microscopical examination the growth showed cell areas varying in size and
separated by bands of fibrous tissue; there was some lymphocytic infiltration around
the fibrous tissue and at the edge of the growdh. The tumour was very vascular, the
vessel walls in many cases being ill-developed. Clustered around the vessels and
fibrous strands running from them were elongated cells with numerous nuclei;
these latter took the stain badly and often appeared quite pale and vacuolated;
the protoplasm took a violet colouration with the Giemsa stain. Some of these
“ cancer ” cells contained typical cell inclusions ” with protoplasm staining pink
and nuclei dark blue or black with the I. G. method, and in the centre of the
larger groups of cancer cells these pink staining cells occurred free in groups.
Sometimes they contained two nuclei, but there was no tendency to the multiplication
of nuclei without cell diWsion seen in the cancer cells proper, and each cell wall
was for the most part separate from its neighbour.

i 'ase 36 .—Ademram of the right Adrenal Bodtf.

G. W., aged 53, was under observation for about eight montlis. He had no
8ympfi)ms beyond a progressive asthenia, but became bedridden and died of broncho¬
pneumonia, accelerated by fracture of the ribs and stemuin.

At the post-mortem examination the right adrenal gland was seen to be enlarged,
and on section a rounded mass, 1 cm. in diameter, was found bulging the capsule on
one side. The remainder (J the gland appeared normal to the naked eye.

On mici\)bcopic examination the rounded mass showed “skeleton” cells, large and

NOTES ON FOETY NEW GROWTHS

269

pale, and round or oval in shape. They occurred in small groups.or columns
separated by blood vessels distended with blood and occasional areas of round cell
infiltration. A fibrous strand in part surrounded by heemorrhage apparently carried
a larger vessel across one edge of the adenomatous nodule. The medullary substance
of the adrenal appeared normal in structure.

A few atypical cells with round, dark nuclei and dear pink protoplasm were seen
scattered about the sections stained by the I. G. method, but they were not greatly
in evidence and only noticed under systematic examinaion with $00 magnification.

f;17 .—Carrimmiii uj ihe Ixircfe Jntpsfinp.

M. E. D., aged 66, had no symptoms of disease preceding deatli, but collapsed
suddenly when walking in the airing court, and died in a few minutes.

At the post-mortem examination collapse of the left lung, hydrothorax, chronic
interstitial nephritis and general enlargement of the thyroid gland were found.
There was a large fungating grovrth (the size of a tangerine orange) at the lower end
of the c«ecum, not involving the ileocsecal valve. No enlarged glands were seen.

Microscopical sections of the growth showed columnar epithelial cells, often
atypical in form and with pale staining nuclei. The growth was infiltrating the
muscular coat, and there was a considerable amount of small round cell infiltration
at the margin.

In sections stained by the I. G. method, cells with pink protoplasm and dark
nuclei appeared in great numbers, both free and as inclusions within the epithelial
cells. They varied very much in size and sha|)e, often appearing as small proto¬
plasmic masses with four or five nuclei. Cells having a similar staining reaction
were seen free in the lymph channels. A very marked feature in this case was the
presence of the pink cells on the surface of the epithelium and within the surface
epithelium.

Case 88 .—Adenoma of th^ Thyroid Gland.

C. H., aged 67 years, died of pulmonary tuberculosis.

At the post-mortem examination tuberculceis of the lungs and tubercular ulcera¬
tion of large and small intestines were found. The upper part of both lateral lobes
of the thyroid glands were enlarged; on the right side a section cut through the
enlarged portion showed yellowish cystic areas with a partly calcified wall ; on the
left side the centre was soft and reddish in colour, the capsule yellow and firm.
There were no adhesions to the surrounding structures.

On microscopic examination the growth showed groups of glandular cells of
various sizes, separated by strands of fibrous tissue. There was a well-defined fibrous
capsule and a good deal of small round cell infiltration. The centre of the tumour
was breaking down, but at some parts of the edge of the growth the granular cells
were quite atypical both in form and arrangement, and there was a good deal of
haemorrhage into the tissue. The cells formed groups of five or six deep or were
arranged in columns, and were often vacuolated and incompletely divided from one
another. In one place the growth appeared to be spreading through the capsule.
Hanging drop specimens made from this growth showed large spindle-shaped cells
very different from those seen in film preparations and cut sections of the growth.

270

AltCHlV£S

Case 39 .—Comcer of the left Adrenal Body.

M. C., aged 73, began to have sudden attacks of dyspncea in September, 1906,
developed cedema of the feet and died of heart failure a month later, although no
cardiac lesion was evident during life. There was dulness at the base of both lungs.

At the post-mortem examination about 10 ounces of fluid were found in the right
pleural cavity and the surface of the lung was studied with white nodules. On
section the substance of all three lobes was intiltrattMl with small white areas often
showing punctate haemorrhages. The upper lobe on the left was solid with a mass
of new growth moderately soft in consistency. The lowei lobe showed scattered
islets of a similar nature. On the upper surface of the left adrenal was a round
whitish mass about the size of a Spanish nut, similar in character to the growths in
the lung. The lymphatic glands around the abdominal aorta were enlaiged, soft
and white, and the bronchial and mediastinal glands were also affected. There w^as
a small polypus of the uterus.

Microscopical sections of the suprarenal growth showed areas of quickly growing
cells with large pale nuclei, and with a protoplasm staining violet. Among these cells
were masses of protoplasm staining a deep pink colour, which were for the most
part non-nucleated, but in some places contained round dark nuclei. The same pink
cells also occurred as inclusions within the cubical, violet staining cells, and could be
seen lying free among suprarenal cortical cells, which were not malignant in
character, i.c., did not show signs of active proliferation.

Sections taken from the growth in tlie lung showed a mass of the pink staining
cells surrounded by a considerable small round cell infiltration, but between the pink
cells and lymphocytes there was always a zone of cancer tissue cells, mostly irre¬
gularly oval or cuboid in shape. These cancer cells contain many of the pink
staining masses, nucleated or non-nucleated, as inclusions. The glands showed
isolated areas and strands of the pink nucleated protoplasmic masses, and at first it
appeared that none of the true cancer tissue cells were present, but one or two
isolated elongated violet staining cells were seen lying in a lymph space.

The sub-muoous polypus was a simple, typical example of the glandular type, with
columnar epithelium lining the spaces and a large amount of mucous glandular
tissue near the base of the growth.

Tills tumour was of interest from the fact that microscopical sections showed that
the growth was spreading in the same way as has been noted in the case of gliomata.
Glandular cells beyond the malignant area shelved early proliferation changes, and
this in a less degree as they were further removed from the growth. There was thus
a gradual transition from normal suprarenal epithelium in one part of the gland to
quickly growing unhealthy cells in the tumour area.

Case 40 .—Canrer of the Gall Bladder.

J. W., aged 64 years, began to have a rise of temperature in the evening about
five months before death, sometimes as high as 103° to 104° at night and falling to
normal or sub-normal in the morning.

There was some pain in the right hypochondrium, and on palpation a hard mass
could be felt in the region of the gall bladder. This mass increased in sifce until
(before death) it reached the mid-line of the abdomen. There was some ascites, about
100 ounces of fluid being withdrawn.

NOTES ON FORTY NEW GROWTHS

271

At the posf-moriem examination about two pinU of clear sherry-coloured fluid
were removed from the abdominal cavity. Around the liver there were numerous
and dense adhesions, fixing the transverse colon firmly to the under surface of a
growtli apparently arising in the gall bladder. The anterior surface of the liver
was very granular, and at the inferior border of the right lobe there was a round
thickened cartilaginous plate. The gall bladder was enlarged and thickened, and on
section was seen to be infiltrated with new growth which had the appearance of
being in a state of disintegration; embedded in it were four or five facetted calculi.
Immediately underneath the cartilaginous plate referred to there was found in the
substance of the liver a large area of new growth, definitely circumscribed, soft
greenish yellow, and at the centre containing creamy pus. The pancreas presented
an unusual appearance, containing dark maroon coloured areas scattered throughout
the entire substance, apparently due to hcemorrhage.

Microscopically the growth was of the typical encephalodd cancerous variety,
consisting of masses of more or less oval cells, taking a purple stain with the I. 0.
method. In the centre of these masses cells containing pink and containing dark
nuclei were grouped, and the same occurred as inclusions within the tumor cells.

There was a good deal of fibrous tissue reaction around this growth, and in the
substance of the liver; the small round cell infiltration was meet marked around the
portal tracts. The bile ducts appeared to be increased in number and size; there
was an undoubted proliferation of the epithelial cells, and in some parts several
layers of cubical epithelium could be seen lining the ducts.

Under a high power the malignant masses wwe seen to consist of cells which
mostly contained pale staining vacuolated nuclei. The protoplasm between adjacent
cells was continuous, and it was impossible to distinguish cell boundaries in many
cases. The isolated cells were most elongated, and suggest a columnar celled
growth. There was a marked intercellular cirrhosis of the liver, and the pancreas
also showed a fibrotic condition with some hsemorrhage.

The Cerebral Growths.

The Notes of Cases 1 to 18 are those of tumours situated within the
cranial cavity Of these, 12 were primary in the brain or membrane,
and confined to that situation; two were secondary to grow^ths arising in
the lung and breast respectively ; three were syphilitic tumours, and one
was tubercular. The four latter cases were included for comparison.

The clinical aspect of the cases does not come into consideration in the
notes, but the question of the possibility of the presence of a demonstrable
physical basis for the mental symptoms in cases of cerebral tumour has
not been lost sight of. It has been suggested by Devaux, Dupre, and
others, that a co-existing diffuse meningitis and encephalitis, as
indicated by definite histological changes, may explain the onset of
mental symptoms in cerebral tumor. A small round cell infiltration
around the vessels of the cortex and membranes was present in 16 of the
cases described above, hut included among these is the case which died

272

AltCRIVti

in Charing Cross Hospital^ in which mental symptoms were neither early
nor obtrusive. Bruns, in the new edition of his work on Tumours of the
Nervous System,’^ states that he does not consider that the changes seen
around tumors are really inflammatory, and there appears some ground
for believing, as will be shown later, that the infiltration by lymphocytes
is not a truly inflammatory condition, but more probably due to the toxic
action of the products of degeneration traversing the perivascular
lymphatics.

Many other writers have discussed the origin of the mental symptoms
in cases of ceiebral tumour, and the general consensus of opinion is in
favour of the view that their onset is influenced by the sise and position
of the tumour. Schuster inclines to the belief that the type of mental
disturbance is dependent in some degree on the location of the growth,
and finds active mental disturbance coincident with tumours of the frontal,
temporal and occipital lobes, while simple mental failure is associated
mote commonly with growths in the parietal and callosal regions. This
was not borne out in the above cases, since, in the four cases of insanity
in which tumour was situated in the frontal lobes, the symptoms were
those of simple dementia or dementia with delusions.

It is therefore impossible at the present time to correlate the presence
of mental symptoms either with the position of the growth, or with the
histological changes, and another factor must be presupposed.

The histological features which have been especially studied in the
foregoing cases of tumor cerebri are those connected with the method of
spread of the growth, the influence on the cortical elements, and the cell
reactions and changes.

In the gliomatous tumours the growth appears to extend in two ways.
In some places cellular areas of glia tissue can be seen invading cortical
and medullary substance, and these areas are often, though not invari¬
ably, connected wdth vessels. But in other parts, where, apparently,
nerve cells and fibres SLve still present, there seems to be a difluse
proliferative influence acting on the glia cells, decreasing in degree as the
section is farther removed from the more cellular growth. This is shown
by the gradual change in the number of neuroglial cells and the presence
of two or more nuclei in one cell. In other words, healthy normal-
looking brain substance passes insensibly into that containing a slight
excess ©f neuroglial nuclei; this in turn is succeeded by tissue obviously
containing neuroglia in abnormal proportions and accompanied by
degenerated nerve-elements, and if the section be followed towards the
centre of the growth, areas of cellulctr glial tissue are seen, in which no
nerve elements are pi’esent beyond patches of degenerated matter.

This condition of growth of the tuitiour for which the brain, as an

NOtES ON Jj’ORXY ^'E\V GllUWTUS

27.j

organ, otters great facilities of observation, would appear to entirely
negative the tlieory that the growth originates from a single cell or group
of cells as far as gliomata are concerned. The condition appears to be
due rather to an inlluence gradually extending beyond the part obviously
alfected, and so acting upon healthy neuroglia, that proliferation of
existing tissue is induced over a considerable area. We are thus led to
the conclusion that a glioma is the result of a tissue change, due to some
undefined cause w^hich transforms healthy neuroglial tissue into quickly
growing glioiuatous cells, and is not traceable to a growth from a definite
cell or group of cells, embryonic or otherwise.

In Case lO, where multiple cancerous nodules occurred in both hemi¬
spheres, secondary to a carcinoma of the breast, the extension to the
brain was obviously along the perivascular lymphatics by w^ay of the
carotid artery. Ihe line oi spread was visible to tne naked eye along the
posterior Sylvian branch of the middle meningeal artery, and Plate 1.
i^Tig. d) shows the growth spreading along a small cortical vessel. After
considerable investigation of these cases 1 am not able to support the
theory of Mr. Sampson Handley, that a small round cell intiltration
is present when rupture of the lymphatic channel occurs from disten¬
sion by the growth. It is certain that, in the brain, rupture of the
lymphatic vessel by the growth may occur without any lymphocytic
infiltration appearing round it (Plate I., Pig. 3), and equally certain,
as shown in Plate I. (Pigs. 1 and 2) that marked lymphocytic infiltration
can be seen around vessels in which tlie tissues and perivascular
lymphatics are quite free from any sign of cancer cells. It would
perhaps be- hardly justifiable to deduce from the above cases, that
the lymphocytosis is not a primary tissue reaction to the cancer cell
growth, but either secondary or the result of a common factor not yet
demonstrated, but as the lymphocytosis without visible growth and the
converse are found frequently in tumours of other organs, the weight of
evidence is against the theory of mechanical injury.

The presence of metastatic groups of tumour cells scattered about the
membranes as far as the vertex of the brain in Case 7, where the tumour
was a circumscribed, localised grow th of the pituitary body, is of interest.
Metastases of primary growths in the brain are uncommon, but Hyde
and Curschman describe a case of secondary cancer where the membranes
were milky to naked eye appearance, and on section showed innumerable
minute secondary foci. The growth in Case 7 was looked upon as an
adenoma of the glandular portion of the pituitary body, and the structure
greatly resembled that of a normal pituitary gland. The growth was
very vascular, but the groups of tumour cells seen scattered over the mem¬
branes were not in any way connected with the vessels, and the only way

8

274

AUCUIVES

in which dissemination can have occurred appears to be through the
cerebrospinal tiuid. It is not easy to understand how the cells were
given oft from the tumour in such a way as to give rise to this condition.

The influence of new growths on the cortical elements has been
incidentally mentioned in the ease of gliomata in the foregoing para¬
graph. These tumours are purely an overgrowth of the neuroglia, and the
convolutional outline in the majority of cases is but little disturbed. The
tumours are mostly slow growing, and it follows that the destruction of
cells and fibres is also a slow, though progressive process. As mentioned
above, the cellular portions of these growths show comparatively little
infiltration and gross pressure on the nerve structures around, and it may
be that the overgrowth of neuroglia and the degeneration of nerve cells
are due to a common cause. Both Bruns and Cornil and Kanvier com¬
ment on this gradually extending aftection of the nerve elements in
gliomata, but consider that it is due to the slow infiltration of the brain
substance by the growth. In the case of the endothelioma and sarcoma
and secondary growths, the infiltrating nature of the tumours cannot be
doubted, and isolated islands of degenerating nerve substance show’ that
the malignant cells have caused degeneration more quickly than it can
be removed. But although the nerve cells in the immediate neighbour¬
hood of the grow-th show chromatolysis and all stages of degeneration,
the evidences of gross pressure on the tissues immediately surrounding
the malignant areas are very few’, and the manner in w’hich the tumour
cells are infiltrating and breaking up the nervous substance at the edge
of the proliferating mass is markedly different from the action which
infiltrating epithelioid or plasma cells have on the tissues in syphilitic
areas. Perhaps the most striking dift'erence is that in malignant
grow^ths, although the centre of the tumour may sliow' necrosis, and small
areas of degenerating nerve substance, yet for the most part, and
especially at the growling edge, the nervous material is broken up and
disappears, and does not remain as a caseating mass infiltrated with
cells.

The influence of the tumour on the vessels of the cortex and membranes
has been noted in most of the cases, and a small round cell infiltration of
the vessels near the grow^th is a constant feature. This lymphocytic
reaction is in many cases completely absent around the growth, and
noticeably so in the gliomatous tumours, but it occurs around the vessels
of the cortex and membranes, and is most marked in the proximity of
the tumour, and usually less so as sections or membranes are examined
further away from the affected area. Endothelial proliferation of the
vessels and perivascular lymphatics was well-marked in three cases, but
w’herever it was seen this change was a slight and recent one, never in

JxOtES ON FOKTi: NEW GROWTHS

27b

the least resembling the endothelial proliferation seen in syphilitic
vessels.

The perivascular lymphocytic infiltration apparently results in an
increase of fibrous tissue around tlie vessels, since within tiie tumours tlie
fibrous condition is the rule, while the lymphocytes appear in large
numbers only at the edge or beyond the growing oorder ui the tumour.
Dilatation and new growth of vessels are apparent in portions of glioma-
tous tumours, and haamorrhage, diapedesis, thrombosis and organisation
of the clot are not uncommonly seen.

In tubercular areas the cell reaction in a greater or less degree
surrounds a central caseating mass. Scattered lymphocytes can be seen
approaching the area from the surrounding vessels, and epithelioid cells
accumulate around the tubercular focus. In no case of tubercle which
has been examined has an infiltration of lymphocytes been seen heaped
up around the vessels, nor has marked endothelial proliferation been
evident.

In gummata of the brain, epithelioid or plasma cells surround the
caseating area, and further out large mononuclear cells of a uniform size,
with small nuclei in proportion to tlieir protoplasm, may usually be seen
infiltrating the substance of the brain. The vessels in these cases often
show proliferation of the endothelium, and there is frequently a marked
lymphocytic reaction around, resembling that shown in Plate I. (Figs. 1
and 2).

The similarity of the tissue changes, and among them the cell pro¬
liferation around the vessels of the brain, in sleeping sickness and general
paralysis of the insane, has been noted by Dr. Mott, and the resemblance of
the changes around the vessel shown in Plate I. (Fig. 2) to those described
by him are very marked. Bose has also drawn attention to the similarity
of tissue changes in cancer and some of the protozoal infections, and the
above-mentioned changes occur also round the vessels in malignant
tumours of other organs.

In malignant growths of the brain, epithelioid or plasma cells are not
a marked feature. Endothelial proliferation, though present, is of slight
degree in the vessels, though more marked in the membranes, and a
lymphocytic infiltration is the prevailing reaction. But a third type of
cell is present in most of these cerebral growths, which is not represented
in any of the tubercular or syphilitic growths of the central nervous
system which I have examined. This is a cell to be described more fully
later, which occurs free and included within the protoplasm of other
cells in secondary growth in the cortex, and which has been demonstrated
in films of gliomatous tissue by newer methods of fixation and staining,
and also in one case of sections of the growth. It is a cell which varies

s 2

27G

ARCHIVES

in size from 1 /x to 20 /i in diameter, and is characterised by a dark, com¬
pact nucleus and a protoplasm taking the eosin stain deeply alter
mordanting with the iodine solution. In the small cells the protoplasm
appears clear and transparent, but in the larger ones a reticulum can be
seen which gives the cell an appearance of having granules which take
a stain slightly deeper pink than the groundwork. Cells of this
type have long been demonstrated in “ cancer ” tissue, and were found in
the secondary growths in the foregoing cases, and also in the cancer of the
pineal gland, but in the tumour of the pituitary body they were repre¬
sented only by extremely minute bodies shown in Plate IV. (l ig. I)> which
were almost too small for any definite statements to be made about them.
Beyond the fact that they are tiny, nucleated masses of protoplasm, little
can be distinguished, but in some instances they were certainly contained
within the protoplasm of the tumour cells. Those figured in the plate
were from the region of a vessel.

Sections of gliomatous tumours have furnished material for the study
of another cell change resulting in a condition known as Colloid ”
bodies.

Bevan Lewis describes these as round or oval bodies varying in size
from 6/X to 40/X in diameter, and occurring frequently in the bruin in
cases of insanity. He says that they are unaffected by aniline dyes, and
considers that the bulk of evidence is in favour of the view that they are
colloid in nature, and are derived from degenerating myelin fibres. In
gliomata tiny homogeneous bodies can be seen within the glial cells,
most frequently in the neighbourhood of the vessels or at the edge of the
cortex adjoining the membranes, and these bodies have been observed
of all sizes from 2/ix to in diameter. Although in their earliist singe
they appear as minute homogeneous bodies within the protoplasm of the
neuroglial cells, taking a faint blue stain with the Iodine Giemsa method,
and pink in the Haematoxylin and Van Qieson sections, yet in some cases
they occupy the whole of the cell and appear to include the cell nucleus.
When seen free in the cortex, the larger ones possess an irregularly
lobulated centre which stains blue with hsematoxylin, and also with the
Gierasa’s solution, while the homogeneous peripheral portion stains pink.

In Case I, these bodies were so numerous at the edge of the cortex in
the Island of Reil that various experimental methods of staining were
possible. It was found that they gave the characteristic blue violet
colour reaction of Chitin when sections were treated with iodine solution
followed by zinc, chloride, the rest of the tissue remaining yellow.

When treated according to the method recommended by Be the for
staining Chitin these bodies appear green, while the rest of the tissue
takes a dark blue colour, but this method of staining is not very convinc-

NOTES ON FORTY NEW GROWTHS

277

ing. When cut in extremely thin sections (2yit) the outer pink staining
portion of the larger bodies is in some cases split or cracked in such a
way as to suggest that the envelope is of a brittle nature. The bodies are
completely dissolved by prolonged exposure to strong acids and to
acidified chloroform. They did not in any case give the colour reaction
of amyloid material, and in the tumour cases they occur in far greater
numbers at the edge of the cortex than in the medullary substance. If
these are the same bodies as those described by Sevan Lewis, the theory
that they are formed from degenerated myelin fibres is not borne out in the
above cases, since their development can be traced within the neuroglial
cells.

Neoplasms in other Organs of the Body.

In the remaining 22 cases of new growths in other parts of the body
than the brain, the symptoms again play a minor part in the notes of
the cases. This is inevitable in the majority of instances, since 12 out of
the 22 gave no signs of new growth during life. Cases 34 and 37,
although complaining of no pain yet liad delusions connected with the
diseased part, which seems to indicate that some sensory impressions were
received from the affected area, although the patient did not translate
the impression in the normal way. The absence of symptoms in Cases
30 and 32 is of interest considering the extent of the stomach which was
involved; the absence of vomiting shows that the reflex nervous paths
must have been much less sensitive than normal.

In considering the pathological anatomy of the tumours in these
organs, the changes which will be dwelt upon are those which are common
to the majority of the growths, namely, those connected with the origin
and spread of the neoplasms and the cell reactions and changes which take
place in and around them.

Origin and Method of Spread.

Tlie systematic performance of 'pod-niortem examinations on all
asylum patients has given an opportunity for the examination of some
early neoplasms. Case 25, a small papillomatous growth in the stomach,
on microscopical examination showed all the changes which are found
more extensively in the larger malignant masses. These are an abnormal
j)lication of the mucous membrane resulting from a rapid proliferation
of the epithelial cells, a separation of the mucous from the muscular layer
by an infiltration of mononucleated and multi-nucleated cells, and a
tendency on the part of the columns and folds of epithelial cells to extend
down into the muscle substance.

278

AllClIlVES

In this early stage inclusions of the mononuclear cells within the
epithelial cells are seen, but a large proportion of atypical pink cells lie
free in the folds and submucous spaces. In the larger growths in this
situation, illustrations of wliich are given, the pink cells with dark nuclei
are a prominent feature. They are seen in groups on the surface of the
epithelium, in groups and singly included within the protoplasm and
nuclei of the epithelial cells, lying free in the lymphatic spaces beneath
the epithelium and in the secondary growth of Case 21, illustrated in
Plate III., these cells were seen invading the kidney substance in far
greater numbers than the epithelium of the cancer tissue, small groups
of the latter occurring only at rare intervals in the section. The early
growths seen in the suprarenal gland showed a similar condition to that
seen in the cells in gliomata, namely, a gradually extending tendency in
the glandular epithelium to proliferation. In Case 39 this was accom¬
panied by the presence of the pink cells mentioned above, some of them
lying beyond the area of active proliferation, and among apparently
healthy columns of cells.

Thus the origin of these tumours also from a single cell or group of
cells seems unlikely, or if this occurs, the malignant tendency must pass
from the original cell to those surrounding it, and the contagion spread¬
ing in this manner continue until the affected area is cut off from the
healthy portion of the gland by lymphocytic reaction and the formation
of fibrous tissue.

We are therefore led to the conclusion that in some of the tumours
originating in glandular epithelium also the growth is not due to an
unending proliferation of a definite small group of cells, but to a gradu¬
ally extending tendency to multiply which spreads around a given focus,
as has been found to be the case in gliomata.

In these early cases the lymphocytic reaction was largely confined to
the region surrounding the vessels, although no signs could be found of
the malignant cells spreading in that direction. On the other hand, the
pink cells are to be found in the perivascular lymphatics beyond the
region of the growth, and Ijdng among the cells which show some
proliferation tendency, but are not yet malignant in appearance.

The lymphatic channels surrounding the growths have been carefully
examined, and in very few of the cases has the epithelial growth been seen
extending along them.

The spread of epithelial cells as a continuous extension of the primary
growth along the lymph channels, as described by Mr. Sampson Handley,
was seen in the above cases only in cancer of the breast, and never around
the primary growth in other organs.

NOTES ON FORTY NEW GROWTHS

:J79

The Cell Reactions and Changes Found in New Growths.

Tbe lymphocytic reaction to malignant growths is a well-known
feature, and has formed the basis of many discussions. Mr. Sampson
Handley considers that an infiltration of lymphocytes around the growth
is due to mechanical irritation and, in the case of epithelial masses
spreading along the lymphatic channels, does not take place until the
growth causes distension and rupture of the vessel it is invading. It was
shown in the section on cerebral growths that rupture in that situation
may occur without any lymphocytic infiltration surrounding the mass,
and that conversely lymphocytic infiltration is more often seen around
vessels which are entirely free from any sign of cancer epithelial cells in
their neighbourhood. Although this condition is not so striking in other
organs, it can be demonstrated in them also, and the comparison, for
instance, of a tubercular nodule with its walls of lymphocytes, and an
adenomatous or cancerous nodule emphasises the difference in distribu¬
tion of these cells. In all the cancerous tissues the vicinity of the vessels
forms a greater attraction for the small round cells than the growth itself,
thus forming a resemblance to syphilitic lesions rather than tubercular.
This naturally suggests that some toxin or irritating body is present or
passing along those channels, and close histological examination fails to
show that this irritant is the cancer growth itself.

The Origin and Distridution of the Atypical Cells Containing a
Dark Nucleus and Eosinophil Protoplasm.

These cells are termed atypical, since they do not conform to any
known t}pe of body cell. As seen in sections stained b)’^ hsemotoxylin
and Van Giesen’s solution, the protoplasm appears yellowish brown, and
the nucleus, which is very well defined, a brownish blue. This is shown
in Plate III., in which sections these cells appeared in great numbers
invading the kidney substance. The tissue was taken from Case 21, the
primary growth being a columnar epithelial cancer of the stomach. In
sections which have been mordanted by treatment with an aqueous
solution of iodine in potassium iodide, and stained by Giemsa’s fluid as
described in the introduction, these cells stand out from the surrounding
epithelial tissue by reason of their much more deeply stained nuclei and
their pure eosinophil protoplasm, which is clear in the smaller cells but
granular in some of the larger ones. Their appearance in the tumour
was that of a pink cell with a blue-black, well-defined nucleus, which
in no way resembles the more or less violet protoplasm and paler blue
nucleus of the tissue cells around.

280

ARCHIVES

As seen in films and sections, the small pink cells bear a great
resemblance to nucleated red cells, but when red corpuscles and the
former pink cells lie side by side, the blood corpuscles are seen to possess
a much more distinct coppery tinge with this stain. The size of these
atypical cells is very variable; many have been seen and drawn that are
extremely minute, so much so that they cannot be distinguished with a
magnification of less than 1,000 and their diameter is less than 1 m-

As inclusions within other cells, they vary from about 2 yu. to 8 ^ in
diameter, and in some cases of cancer of the stomach much larger multi-
nucleated masses have been noted as inclusions. When lying free among
the cancer tissue cells they average about 12 in diameter. Unlike
quickly-growing cancer cells, they seldom form multi-nucleated masses,
though these may be seen, but the protoplasm of each cell usually appears
to be distinct from that of its neighbour, and is irregular in shape.

The above cells not infrequently appear as masses of protoplasm without
any nucleus both within and without the epithelial cells, and on this
account give rise to the necessity of considering the possibility that they
are some degenerate form of the cancer tissue. This possibility is
enhanced by the fact that degenerated material also takes an eosinophil
stain, and the position of these cells in the cases examined has not borne
out the statement made by Plimmer of what we believe to be similar cells,
that they do not occur in degenerating parts of the tumour, but at the
growing edge. It is true that in our cases they have been found invading
tissue on their own account, as for instance in Cases 21 and 39, and
beyond the margin of the tumour cells proper, but in Cases 10 and 19 they
occur within the mass of epithelial tissue, their relative position as regards
cancer c^lls and small cell infiltration being well shown in Plate IV. (Figs.
7 and 13) from Case 19.

When seen as non-nucleated bodies within the protoplasm of cancer
ej)ithelium, they might well pass for a colloid degeneration of the cell,
although their other features do not bear out this supposition.

It is believed that the cells described here are identical with those
noted in the first place by Thoma as cell inclnsions, and investigated in
this country by Plimmer, Puffer, Walker and others. They are men¬
tioned by many writers as occurring in malignant growths, and when
present in large numbers (as in some of our cases) are described as
second type of cell with clear protoplasm and a dark nucleus.”

The staining of all the tumours with the modification of the Giemsa
method has demonstrated the identitv of staining reaction of these clear
cells with those found in fewer numbers in other tumours, and with the
smaller bodies occurring as inclusions within the protoplasm of other
cells.

NOTES ON FORTY NEW GROWTHS

281

Plimmer found them in 88 per cent, of his cases, but they were found
only in 25 out of 36 of the above cases, or 70 per cent. Although it is
believed that these are the same bodies as those described by Plimmer,
it is impossible to be certain of that fact, as he describes them as having
a small amount of protoplasm and a capsule, whereas by all the above
methods of fixation or staining, no capsule has been demonstrated either
in the sections, in stained films, or in hanging drop preparations. In
the latter these bodies appear to be composed of a more highly retractile
substance than the protoplasm of the cell which contains them. They
may be nucleated, but are often not so. When stained with 'Wital ”
methylene blue, the retractile bodies take up the stain more quickly and
more intensely than the cancer cells proper, but Toison’s fluid appears
to leave them unstained.

No cell of this type and staining reaction has so far been demonstrated
in blood films or in syphilitic or tubercular tissue stained in the same
way, and it was never found in films of the cerebral growths until a rapid
method of fixation was adopted. In films prepared by the wet method
the pink cells, thougli recognisable to an eye accustomed to looking for
tliem, could not be demonstrated in any great numbers, and mostly
occurred as non-nucleated masses. It would therefore appear that these
cells break up very quickly in films fixed in the ordinary way, and require
very quick fixation for their proper definition.

At least three explanations are possible as to the origin of these
cells: —

1. That they are some hitherto little-known tissue cell brought
into prominence by the neoplasm.

2. That they are some modification of the tumour cells tliemselves
due to regressive changes.

3. That they are extraneous bodies.

1. In support of this supposition it must be urged that it seems the
most probable solution. The cells are most certainly found on the surface
of the mucous membrane of the alimentary tract, but they may have been
exuded from the surrounding tissues where they occur in great numbers.
The wide distribution of the cell is in favour of this explanation, for they
have been found in malignant tumours of all varieties and in all situations,
and in the lymph channels in all organs of the body affected by malignant
growths. Their variation in size is not without analogy in the micro¬
blasts and megaloblasts seen in the bone marrow in pernicious anaemia,
but their presence in the body as a normal constituent has not yet been
demonstrated. If this solution is the correct one, it is rather difficult to
understand why they should take up a position in the centre of the tumour

282

ABCHIVES

cells, and why they should appear in such great numbers on the surface
of the epithelium in tumours of the alimentary tract.

2. The possibility of these bodies being due to a regressive change in
the tissue cells of the growth seemed very great as long as the small cell
inclusions and isolated free cells were looked upon as the only repre¬
sentatives of the class. But the newer methods of staining have linked
these on to the larger cells, which have so wide a distribution that the
theory of endogenous cell proliferation discussed by Virchow, Boyce and
others is hardly tenable. The same may be said of the suggestion that
these bodies were due to colloid degeneration of the tumour cells, since it
seems hardly feasible that large areas of cells should show complete
colloid degeneration of their protoplasm, and that no transitional
forms should be seen between these cells and the tumour cells from
which they might be formed. The bulk of evidence appears to be in
favour of these bodies being distinct entities; their nuclei always difEer
entirely from those of the tumour cells, and it seems improbable that a
nucleus such as is seen in the latter, with its chromatin broken up and
arranged for the most part in a network, should have given rise to the
dark mass seen in the cell inclusion without any intermediate stages
being visible. The protoplasm of the inclusions also has very distinct
characters; in the young and small cells it appears clear and homo¬
geneous, but in the older and breaking down cells a distinct granular
appearance is noticeable and depicted in Plate IV. (Pigs. 12 and 13).

The presence of these pink bodies in films where they appear as
extremely virile cells, having no degenerative character, and their
occurrence in such varied structures as endotheliomata, gliomata
and epithelial cancerous tissue is against them being a degenerative
change, especially as we have shown that the degenerative changes,
probably colloid in nature, which do take place in gliomatous tissue and
which we have never found in malignant growths of other organs, show
quite other characters than the atypical cell. As shown in Case 29,
degenerating cells are also seen in the epithelial growth without any
evidence of the pink cells either free or as inclusions, and this was in a
case in which it may be presumed that the tissue reaction was sufficiently
good to control and kill the growth. In a paper on cell changes in
dourine and sleeping sickness the possibility of the inclusions seen in
those tissues being due to degenerative change was considered. In
those tissues a very prevalent form was a cell with a crescentic nucleus.
It seems worthy of note that this crescentic form has not been seen in
any of the tissues examined here either in the degenerating material or
free in the tissues of either cancer, syphilis or tubercle.

3. 'No proof can be offered at the present time that the atypical cells

NOTES ON FORTY NEW GROWTHS

283

are extraneous in origin, although this view is held by many able patholo¬
gists. It is suggestive that they occur in such large numbers in both
early and advanced malignant disease of the alimentary tract, and that
they are to be seen in considerable numbers on the surface of the epithe¬
lium. It would appear also that they are capable of invading tissues
in secondary growths without the intervention of the cancer epithelial
cell, and that in the majority of growths examined their situation is in
the centre of the epithelium, where tissue celjs reacting to the growth
would hardly appear. Their variation in size, the difference in character
of their nuclei, and their reaction to the same method of staining as the
bodies s6‘on as inclusions and free in the tissue in dourine and sleeping
sickness, are interesting facts, but in the absence of experimental inocula¬
tion into animals nothing definite can be said on this point.

Ti mouk Cell CiLANCiEs.

riimmer has pointed out that the cells in a malignant growth are not
necessarily like their parent cells either in size, shape or staining reaction.
The change in tlie type of cell has been very noticeable in some of the
above cases. In Case 11 the growth consisted for the most part of small
round cells, but a few areas consisted of larger oval cells of the type
seen in the endotheliomata, and their })osition was such as to suggest
that the larger cells formed the primary focus. In Case 31, again, cells
were seen obviously stamping the growth as one arising from the epithe¬
lium of the cervix uteri, and yet the greater part of the primary
malignant mass and t!ie whole of the secondary consisted of elongated
spindle-shaped cells. It has also been frequently noted how much the
secondaiy growths in glanjds resemble one another; a columnar-celled
carcinoma of the stomach or intestine frequently results in a spheroidal or
cuboid secondary mass in the glands, wliich is hardly distinguishable
from a secondary growth following cancer in the breast or other region.

The source of the extra nutritive material which is required for rapid
formation of new cells has long been an object of inquiry. It has been
mentioned above that in the larger secondary growths which infiltrate
organs like the liver, signs of pressure on the surrounding tissue are
rarely great, and in many places quite absent. In spite of this fact very
little debris of liver cells is seen among the cancer cells, except at the
growing edge, and in that situation the cancer cells can be seen in some
cases enclosing, in others growing into and splitting up the tissue cells
of the part. It seems not improbable that the cancer tissue may in this
way acquire some of the nuclein and other material necessary for its
growth. But, if we concede this, we have to consider how these cells.

284

ARCHIVES

which originally arose from the epithelium lining the stomach, acquired
the power of breaking up and devouring other tissue cells, and for an
explanation we must look to the early stage of a growth.

We saw there that the epithelial cells contained what we have called
“ atypical cells within their protoplasm, and that these cells were often
non-nucleated. Is it not possible that these cells, whatever their origin,
mav be responsible for the malignant character of the epithelial growth ?
It is obvious that the ‘‘ atypical cells consist of a nucleus and proto¬
plasm. If these cells are ingested by the epithelial cells, and their
nuclei absorbed, the cell having this extra supply of nuclein manu¬
factured for it would start to proliferate, and it is not difficulf to imagine
that having once acquired the habit of ingesting animal cells, it would
attack any other cells which it met, and that malignant cells do largely
ingest such cells as leucocytes and lymphocytes is generally conceded.
In this way it may ingest the connective tissue, eat its w^ay through the
muscle substance, and, increasing in strength and virulence as it proceeds,
become truly cannibalistic and form the rapidly growing masses which are
so often seen in secondary growths.

Summary and Conclusion.

It has been seen in the foregoing pages that in the case of gliomata
of the brain and of primary tumours in some of the glandular organs of
the body, the growth of the tumour is due, in pfirt at any rate, to some
influence which acts over a wide area and appears to extend gradually
around a given focus, causing proliferation of the cells of the organ. In
the cases examined this focus has been a definite area of malignant cells,
and the proliferation has decreased the farther the section is examined
away from the malignant area. The active influence w^hich causes this
gradually extending tendency to multiply is at present undetermined.
The fact that the most marked lymphocytic reaction is found around
the vessels in the neighbourhood of the growth suggests that some toxic
or irritant body is present in, or passing along, the perivascular channels.

The source of the extra nutritive material required for the rapid
proliferation of tumour cells cannot be definitely determined, but the
conditions of growth in some of the larger organs, such as the liver and
brain, suggest that the invading tumour cells are not only phagocytic and
remove the dead tissue which they replace, but that they are definitely
cannibalistic, and attack the living cells of the organs.

In 25 out of 36 cases of tumour examined by new methods of staining,
cells are found which have a distinct coloration. They consist of an
eosinophil protoplasm, which is clear in the smaller and younger cells

NOTES ON FORTY NEW GROWTHS

285

and granular in the older ones, and a well-defined dark nucleus, which
is sometimes multipartite but more usually single. These cells occur
free in the subvstance of the tumours, on the surface of the epithelial lining
of the alimentary canal, as inclusions within cancer cells, free in the lym¬
phatic spaces, and alone in large numbers in the tissues in cases of malig¬
nant growth. By these methods of staining the bodies differ from those
described by Plimmer in that they possess no capsule, and their nuclei are
not refractory to heeiuotoxylin, although by the hseniotoxylin methods of
staining tliey are not differentiated from the tissue cells around. It is
believed that they have not hitherto been noted in gliomata, and their pre¬
sence in considerable numbers around the vessels in the cerebral tumours
and absence in syphilitic and tubercular lesions of the brain is significant.

In conclusion I wish to express my great indebtedness to Dr. Mott,
the Director of the Laboratory, who placed the material at my disposal
and has given every facility and much personal help in the examination
of the above growths. The very excellent illustrations are the work of
Miss Kelley, and were drawn for the most part by the aid of the Camera
liueida.

REFERENCES.

Bevan Lewis. “A Text Book of Mental Diseases.”

Bonney. “A Stud}^ of the Connective Tissue in Squamous Cell Carcinoma and in
certain pathological conditions preceding its onset.” Archives of the Middlesex
Hospital, vol. ix., 1907.

Bose. “ Les Maladies Bryocytique.” (Jeyitralldaii fur Barteriologie, 1904, el sejp

Bruns, Di*i Geschwiilsfce des Nervensystems.'* Zweite Auflage, 1908.

CoRNiL ET Ranmkr. “ Maniiel d’Histologie Pathologique,” Tome III. Troisieme
Edition 1907.

Damayk, Henri. ‘'Observations d’uii Ca^s do Debilite Mentale avec. impulsions et
irritabilite ; a rauto[)sie sarcome angiolitique du lobe frontal gauche.”

Dupre, E , et Devaux, A. “ Abci's cthebral, necrose corticale, .syndrome meninge.”
Nouv. Iconogr. dv In Snl 2 )(Hr, No. 3, p. 239.

Farmer, Moore and Walker. “Leucocytes in Malignant Growths.” Trans. Path.
Soc. Vol. xlvi.

Handley, Sampson W. “ Cancer of the Breast and its Operative Treatment ”
(Murray, 1906.)

Idem. “ The Pathology of Melanotic growths in relation to their Operative
Treatment.” The Ijancet, April 6th, 1907.

Harvey. “Experimental Lymphocytosis.”

Hyde dnd Curschman. “ On Generalised Metastic ('arcinoma of the Central Nervous
System.” {Arbeiten aus path. Tustit. zu Tubingen.)

Klippel, M. “ Enc^qdialite avec Confusion Mentale Primitive.” iyEnc(phole,So. 4,
p. 359.

286

A&CHIVES

Klippel et Ranaed. “ Note snr rHistogeoese d’lin Epithelioma seconclaire du
Cerveau.” Revue du Medecin au ‘27, 10 Janvier, 1907.

Mott and Stewart. “ Further observations on the Cell Changes in Sleeping Sickness
and Dourine.’* Brit. Med. Journal, vol. ii., 1907.

Oertel. “ On the Histogenesis of Tumours.” Rockfeller Institute Report, vol. vii.,
1907.

Oetmann. “ Gynaecological Pathology.”

Oppenheim UNI) Cassirer. “ Die Encephalitis.” Zweite Auflage.

Plimmer. “On the Etiology and Histology of Camter.” The PractUiouer, A\)r[\y 1899.
“ Reports of the Cancer Research Laboratories of the Middlesex Hospital.”

“ Reports of the Cancer Research Fund.”

Rupert Boyce, M.B., and Artuur Giles, M.D. “On Cell Enclosures in Cancer.”
Trans. Path. Soc. 1893.

Sutton Bland. “ Tumours Innocent and Malignant.”

Virchow. “Die Ge.'^chwiilste.”

Walker. “On the Vesicular Structures in Malignant Growths.” Trans. Path. Soc.
Vol. xlvi.

Zeigler. “ Pathological Anatomy.”

DESCRIPTION OF PLATE I.

Fio. 1.—A vessel from.the cerebral cortex in Case 10, beyond the edge of the cancer growth
showing infiltration with small round cells and no cancer cells. Stained by lod., Giemsa
method. Magnification 230.

Fig. 2.—Sliows a similar infiltration around a cortical vessel beyond the growth in Case 4 of
glioma of the temporal lobe. Stained by lod., (liemsa metho<l. Magnification 280.

Pig. 3 .—A vessel in the vicinity of the growth from the same section as Fig 1, showing exten¬
sion of the cancer cells around a central vessel. Although the growth has obviously
burst through the perivascular lymj>haric channel at the lower juargin. there is an entire
absence of lymphocytic infiltration around the growth. Stained by lod., Clierasa meth(xl.
Magnification 52U.

PLATE I.

Fui. 1.

Fk;. 2.

Fig. 3.

face p. 2Hfi.

PLATE I!

Fig. 1.

Film ])re|)aration from a glioma,

AAA Atypical cells with dark nuclei. ^Magiiihcaiion 400 .

Fig. 2.

Cells from Fig. I under a higher ma^rniticalion, with a tvi>ical
glioma cell—B. Afagnitication

NOTES ON FORTY NEW OROWTIIS

287

DESCRIPTION OF PLATE III.

A sec.nndary nodule in the kidney from a case of carcinoma of the stomach (Case 21),
showing the mononuclear cells seen in the primary growth, but no columnar epithelium.
Magnification 250.

28S

AltCU 1VKS

DKSCRIFTIOX OF PLATE IV.

The atypical pink cells menlioned in the text as they app(‘ar free, and as inclusions in tumours.
Scaioed by lod., G-iemsa method. Magnificatioa 1,0U0.

1.—A large cell (atypical) in cancer of stomach (Case 20, II.)

TI.—A similar cell, more deeply stained.

III.—A small cell inclu.sion from a case of cancer of the intestine (Case 37).

IVL—A similar cell from a case of Jenson’s tumour in mice.

V. —A cell with two inclusions, fnim the gland of a dog inoculated with Tryparurntma Kqvi-
perdum,

1 to 10.—Isolated cells of all sizes from different tumour eases. 1.—From Case 3.

2, 3, 4, 5.—From the lymphatic spaces of Cisc 10. The granular protopla.sm in 4 and o is well
marked.

6, 7, 8, 9.—From cases of .lensen's tumour in mice.

10. —From a hyaline space in tumour of the pineal glan«l.

12 and 13.—From a film preparation in cancer of stomach (Case 22).

11. —Is a hnI blood corpuscle, ami 14 a cancer cell from the same film as 12 and 13, to show

relative size.

PLATK IV.

larr p. 2SS

‘289

A. DESCRIPTION OF THE BRAIN OF AN EPILEPTIC IMBECII.E
SHOWING EXTENSIVE HETEROTOPIA OF THE GREY MATTER.

BY HEI.K^r G. STEWART. M.l).,

Fnnn the Pnihahujiad hihoniinri/ of the London ('oniitij Asfjtnms, (dloyhnrf/.

Contents.

1. History of the Patient.

jPodi-morfeni appearance oi‘ tlie external conHii^uration ot the Bi'aiii vvitli weiglits
and photographs.

II. Description of internal structure with sections illustrating:—■

1. Frontal region ) vertical sections.

II. ('entral region ) liorizont^il sections.

111. Occipital region.

HI. Account of the Tnicroscof)ical examination with illustration of cortex of the
central region as coin})ared witli the same region in a normal adult brain
and that of an infant aged six weeks.

IV. Short account of ca.ses hitherto desc ribed.

V. (’onclnsions.

Through the kiudue.s.s of l)r. Mott 1 have had the opportunity of
examining the brain of a female epileptic imbecile who died in Claybury
Asylum at the age of -37 years, which presents some interesting features.

I'he clinical history is as follows: As an infant she was very back¬
ward, could not walk until she was three years of age, and could onl}^
accomplish the most elementary acts. She was taught to dress herself,
but never learned to sew or do housework, and could not be trusted to
“ run errands.'’ She had no infantile illnesses, but when eight years old
started to have fits at night and afterwards in the daytime. From that
date she gradually became unmanageable, was sent to the workhouse at
the age of 11, and from there to the asylum, where she has remained ever
since. She was transferred to Claybury from Leavesden in July, 190G,
on account of attempted suicide after a fit. She was said to be of quite
the lowest type of humanity, of stout build (in a struggle which often
occurred at bed-time she required five or six nin*ses to put her to bed),
with a heavy under jaw and a powerful animal set of teeth. Her mental

T

290

AECHIVES

state was that of complete imbecility; she could not recognise the doctor
or nurse, and only knew three things—her dinner, which she gorged, an
old rag doll, and some reels with which she was accustomed to play;
with these exceptions she was oblivious to her surroundings. She was
generally noisy and screaming, but her speech was childish; she would
say, ‘‘ Me want my reels.’^ Her fits were typical and severe, occurring
about twice a month and often at night; there was no petit mol.

She died of pulmonary tuberculosis witii terminal gangrene. The
parents were healthy; they had ten children of whom the patient was
the eighth. The sixth child was also mentally affected at an early age
and died in an asylum.

Post-mortem examination ,—When the calvarium was first removed
very little abnormal was noticed. There was slight thickening of the
pia and a slight excess of cerebrospinal fluid. The brain weighed
1,040 gins., the right hemisphere 440 gms., the left hemisphere 415 gms.,
pons and cerebellum 155 gms., and the loss of weight after stripping the
membrane was 35 gms. for each hemisphere. The normal average brain
is about eight times the weight of its pons, medulla and cerebellum; con¬
sequently the deficiency of 200 gms. (8X lo5=l:;^40^ was an indication of
failure of development of the cerebral hemispheres.

The brain was also under the average normal weight for that stature
(Quain giving the average for 5 ft. 3 ins., the height of patient, as
1,218 gms.), and the loss from wasting, as estimated from the excess of
cerebrospinal fluid and thickening of membrane, does not account for the
difference ; it was, however, not sufficiently undersized to be considered
microcephalic. On examining the brain after removal it was found to be of a
very low type of development. The most stril^ing features were the shallow¬
ness of the sulci and an absence of frontal operculum which left the
upper part of the insula uncovered; it was impossible to determine the
upper limit of the Island of Reil from the external surface, but the small
fissures (AA in photograph) probably represent the sulcus limitans insulae.
The Sylman -fissure slanted obliquely upwards on both sides, as is well
shown in this photograph of the external surface (Plate I.), making an
angle of 47^ w ith a straight line drawn from the anterior to the posterior
pole. The third frontal convolution was continuous w ith the Island of
Reil along the whole length of the fissure on the right side, although in
the left hemisphere there w'as a slight degree of overlapping in the
parietal region. The remaining fissures were elementary; the fissure of
Rolando was short and shallow, measuring (after hardening) only 5 mm.
at its deepest point; the calcarine fissure ended at the posterior pole on
both sides and the line of Gennari just beyond its termination. This
latter fissure w\as the deepest in the brain fl’5 c.ni.), the only other which

PLATK I.

Photograph of right and left hemispheres of brain of epileptic imbecile, showing shallow
fissnres and poverty of secondary markings. A. A. slight indentations representing

Sulcus limitans insulae.

Face p, 290.

PLATE II.

(

(

\

A3 / B3

A 1.—A Tertical section through the central region of tlie left hemisphere stained by Nissls
method for cells.

B 1.—Section from the same region stained by the Kulschitski-Pal method for fibres.

A 2,—Vertical section through the frontal region (Nissl’s method).

B 2.—The same as A 2 stained by the Kulschitski-Pal method.

A 3.—Horizontal section through the occipital re^on (Nissl’s method).

B 3—The same as A 3 stained by the Kulachitski-Pal method.

Fare p. 291.

Examination of brain of epileptic imbecile

291

approached a normal depth being the collateral, which measured 8 mm. at
its deepest part.

The parieto-occipital fissure on both sides was shallow, especially at
the mesial border, where the floor of the fissure was visible 3 mm. below
the surface. The calloso-marginal fissure was fragmentary on both
sides and ran within a few millimetres of the callosal fissure until it
reached the central region.

The secondary fissures were sliort and shallow, the average depth of
all sulci, with the exception of the calcarine and collateral, being 4 mm.
The temporal loBe was best developed both in size and in the complexity
of its convolutions.

II.

Internal structure ,—On section the cortex was found to be only slightly
narrower than normal, but beneath the cortical grey matter throughout
the whole cerebrum, with the exception of the fornicate and hippocampal
gyri, was a deep grey band. On microscopical examination this band
proved to be a second deep layer of nerve cells, which was separated
from the cortex by a well-defined streak of white matter. The accom¬
panying illustrations (Plato II.) were drawn from sections through the
frontal, central and occipital regions.

Figs. Al, A2, A3, were stained by Nissl's method for nerve cells;
Figs. Bl, B2, B3, by the Kulschitski-Pal method for fibres. The
approximate depths of the various regions are given below: —

Prefrontal ...
Frontal
Parietal
Occipital ...
Temporal ...

I)Ei*TH OF Cortex

I'o mill,
l o mm.
i s mm.

I'o mm.

2*0 mm.

Depth of sub¬
cortical LAYER.

5 mm.

9 mm.

11 mm.

8 mm.

5 mm.

Accurate measurements were rendered difficult on account of the neces¬
sity of making an arbitrary point for the ending of the polymorphic
layer, since in most parts the cells of that layer were continued down into
the sub-cortical portion.

The cortical depth is rather over than under estimated, and, therefore,
allowing for equal error in each case the occipital and temporal cortex
show a preponderance over the other areas. The depth of the temporal
cortex corresponds with the animal type of bodily development, and is
an interesting feature. The sub-cortical layer tapered out just beyond
the base of the calloso-marginal and collateral fissures, but microscopic
investigation showed the presence of isolated cells scattered throughout

T 2

292

ARCHIVES

the white matter of these gyri. The sub-cortical layer appeared con¬
tinuous with the claustrum, but a true claustral formation was wanting
on both sides, the cells in this situation consisting of groups of pyramidal
and other cells lying between the layers of fibres through which spindle
cells were scattered. On the right side this region was broken up by
a narrow, poorly developed band of white fibres, but no marked differ¬
ences occur between the type of cell on either side of this division. The
basal nuclei appeared normal in structure although the lenticular nuclei
were smaller than usual, and consisted chiefly of putamen, the globus
pallidus being only faintly indicat^ed in nakcnl eye specimens (Plate II.,
rig. Al).

III.

Microscopical examination ,—The most striking histological feature in
all regions of the superficial cortex was the immature condition of the
cells and the deficiency in depth of the pyramidal layer. Fig. 2,
Plate III., was drawn from a section taken from the top of the ascending
frontal convolution, and to compare with it Fig. I, Plate III., and Fig. I,
Plate IV., were taken from the same part of a normal adult brain and
that of a six weeks’ old infant respectively.

The abnormalities seen in this area are on the whole representative of
those seen throughout the brain with the exception of the hippocampal
gyrus, which approximates to the normal.

The cells in all regions are seen to be either embryonic or infantile;
the outline is more often convex than concave and they have large nuclei
and few processes. The zonal layer is narrow and either contains larger
cells than are normal in this situation or the cells seen here really belong
to the layer below; they do not conform to the three types described by
(.’ajal, but are either round and quite embryonic or polygonal.

The small pyramidal cells are crowded together, are more triangular
in shape than is usual, and the nuclei are large and pale.

The average size of the medium pyramidal cells is smaller (16 by 8)
than in the normal cortex; the largest cells noted in this layer measured
24 by II. Both this layer and the last are narrower than normal, as is
seen from a comparison of the strips (Figs. I and 2, Plate III., and Fig. 1,
Plate IV.), which were drawn with the same magnification by means of
the camera lucida.

The large pyramidal layer in the central region contains cells up to
the size of 32 by 19, i.e., practically the normal size, but very few had
any indication of Nissl granules. The Betz cells were Somewhat
abnormal in distribution. On the lateral surface of the hemisphere
they were only found in about the upper fifth of the ascending frontal

PLATE HI

Fut. 2 . Strip of opileptic irnbfcile brain,
central region (Nig:»l).

PLATE IV.

Fl(i. 1. Strip of infant's Ijrain, central region (XissI),

J nrr 29 ).

Cells from the sub-cortical layer of grey matter in the Heterotopic brain.

1. ii^iuined by the Bielsohowsky method for introcellular libre.

2, Stained by Nisal method.

PLATK VI.

I

In;.

r.n,

I

1

I

I

Strip of noniKtl hrain. c-Mtr.il
rouioii Uvi Uci'.i’'■ki-Pal ).

I !<;. 2. Stri]» of epileptic imV)ecile brain,
central rejzion (Kulschitski-
Pal).

EXAMINATION OF BKAIN OF EPILEPTIC IMBECILE

293

convolution, but ou the mesial surface they extended to within 1 cm. of the
callosal fissure. The largest cells of this type on the mesial surface
measured 64 by 22, equal to about the average size Betz cell found in the
lateral surface in normal brains.

The granular layer was of quite average development in all regions
and the reduplication in the visuo-sensory area was well marked.

The cells in the sub-cortical layer were irregular in arrangement and
distribution. As before stated, this layer was not visible to the naked
eye as a grey area in the hippocampal or callosal gyri, but well-formed
isolated cells were scattered between the fibres in these situations also.
This layer formed a continuous deep belt of cells, but the lower edge of
the belt was broken up into islands by bands of fibres.

No definite layers were discernible in this sub-cortical zone of cells.
The cells lie at all angles, but a general view with the low power shows
that there is a tendency on the whole for the apical process to point
towards the cortex and the base inwards. The pyramidal type of cell
predominates, but many polymorphic and immature cells are present.
The apical process and axon aie well marked, but the number of proto¬
plasmic processes varies greatly; in some cases they are numerous and
short, in others (bipolar or spindle-shaped cells) there are only two or
three. Like the cortical cells proper they have large pale nuclei often
occupying the greater part of the cell, and the cell body is flat and
granular. Some of the larger pyramidal cells in this area show Nissl
granules, as is seen in Plate V., 2; these cells were drawn from the sub¬
cortical region beneath the motor area.

The intracellular fibrillation, as shown by the Bielscliowsky method, is
poor, both in cortical and sub-cortical regions. In many cells the
fibrils are only apparent in one part of the cell and, as shown in Plate V.,
some quite large cells contain only a few isolated fibrils. Still, the
presence of these fibrils and of Nissl granules proves without doubt that
the cells of the sub-cortical region were functionally active to some
degree.

Herxheimer and Gierlich state that traces of intracellular fibrillation
can be demonstrated in the brain of a six months’ old foetus, but the cells
of the motor area of the infant aged six weeks which was examined by
this method failed to show any intracellular fibrillation, although a few
extra cellular fibrils were present in that area.

The fibre layers of the cortex were incomplete in many instances,
and the most noticeable feature of the sections was the deficiency of
transverse fibres. This was most marked in the radial zone, as seen from
the illustration (Fig. 2, Plate VI.). The sensory areas are better
developed in this respect than the motor; in the visuo-sensory region

294

AHCHIVES

both outer and inner line of Bailiarger are well marked and the tangen¬
tial system generally is better developed than in the central region.

The resemblance of the type of cell and fibre in this cortex to that
of the infantile brain is marked and some estimate of it can be formed
from the illustrations. A large number of the cells of the cortex as well
as those in the sub-cortical region are of embryonic type, and the
development of intracellular fibrils is very defective. The fibres also,
in their wavy margin and small calibre, resemble the defectively
myelinated fibres of a developing brain (Plate YII., Figs. 2 and 3).

Besides the structural defects mentioned above there was some excess
of neuroglial nuclei; the vessels were engorged and showed the dilation
of perivascular lymphatics, which is common in epileptic brains. There
was no indication, in any region, of old or recent inflammatory conditions,
and no patches of sclerosis were found. Both uncinate regions appeared
normal, and the structural defects described were the only noticeable
abnormalities.

IV.

Other cases of heterotopia ,—Virchow defined heterotopia of the cortex
as grey matter occurring in positions normally occupied by other struc¬
tures, and Anton, though stating that the most usual form is that of
isolated areas of cells in the neighbourhood of the ventricular walls,
mentions the occurrence of grey matter in the substance of the corona
radiata, the cell elements of which comprise pyramidal and spindle
cells as well as small round ganglion cells. The convolutions or cortex
over these areas are, according to Anton, highly deformed or microgyric.
Meine describes a case where macrogyria was present in the parietal
region and the internal structure of that lobule consisted of grey matter
for two-thirds of the distance from the external to the ventricular surface.
In the superficial portion all the usual cortical layers were represented,
but the deeper part, though containing cells of all varieties, was not
differentiated into layers. This case, like several of the others reported,
was accompanied by some meningitis. In his article Meine gives
summary accounts of 13 cases reported by various writers up to that
date (1897).

The cases vary in severity; one described by Ehrman having no
psychic affection during life, yet showed extensive abnormal areas of
grey matter in the walls of the lateral ventricle post mortem. Another
case reported by Tungel only had mental affection after reaching the
age of 31 years and about four weeks before death. Four other cases
have been described which bear a considerable resemblance to the one
with which we are dealing.

PLATE VII.

Fk;. 2.

Fibres from inner line of Baillager. Heterotopic brain.

Fn;. :b

Fibres from sub-conio;il region (ctmtral) Infant's brain.

EXAMINATION OE BRAIN OF EPILEPTIC IMBECILE

295

KolscLitkowa reports a case of epileptic idiocy in a girl of six years
of age in which the brain showed islands of grey matter in the medullary
substance; the islands were composed of undilterentiated neuroblasts.

Winkier (Utrecht) describes the brain of an epileptic dement (aged
20 years) with a complete layer of sub-cortical celJs, ^ c.m. broad,
running paralle] with the cortex from the frontal to the occipital region.
This layer, which was not present in the temporal lobe, consisted of
polymorphic and pear-shaped ‘'ganglion*’ cells often of an embryonic
type. There was some chronic inflammation of the pia.

Matell gives a full account of a female epileptic imbecile dying at
the age of 25 years who, both in history and cerebral conformation
closely resembles the case we have described. Not only does the sub¬
cortical layer of cells occupy very much the same extent and position,
but Matell notes a deficiency in pyramidal cells of the superficial cortex,
and mentions that the polymorphic layer is continued down into the
subcortical medullary substance.

The fourth case, reported by Tedeschi, is that of a child, also an
epileptic, with a brain of similar structure although the occipital region
appears to have been less well developed than in our case. This writer
notes the diminution in size of the nerve fibres.

All four of the above cases were epileptic, and, according to Anton,
the condition of heterotopia is usually associated with epilepsy; but of
the cases mentioned by Meine only five had fits, and these were cases
having fairly extensive cell areas in some part of the corona radiata;
the remainder of the cases had abnormal islands of grey matter in the
region of the walls of the ventricles and were either unaffected mentally
or subjects of insanity occurring in later life. In some of the epileptic
cases the fibres are noted as being of deficient calibre and in most the
cells or cortical development are described as embryonic. As suggested
by Roncoroni, and ably supported by the investigations of Dr. J. Turner
in this country, a persistence of subcortical cells (they were found
presejit in a greater or less degree in from 70 to 80 per cent, of epileptics),
together with other infantile characters, are the most constant structural
defects in the epileptic brain. When we consider how slight a condition
of toxaemia is sufficient to cause convulsions in infants it is easy to
understand that, should embryonic or infantile features persist through¬
out life, a similar susceptibility to fits would also continue from causes
insufficient to give rise to more than a passing indisposition in adults.

Y.

Coiichtsions .— It would appear then froni the above account that this
case, while conforming to Virchow’s definition of heterotopia of the

296

AECHIVES

cortex is in fact a mal-development, of which, slighter degrees are not
uncommon in the brains of epileptics. In other words, it is a persistence
of sub-cortical nerve cells in a high degree, these cells having matured
to the extent of exhibiting many functional characteristics. Whether
this persistence and maturation is due to a compensatory effort on the
part of the organ to supply the defect in the number of cortical cells
which must have resulted from the elementary state of the fissures, or
whether it is part of a general under-development, it is impossible to say.
The defective myelination of the nerve fibres and poverty of intra¬
cellular fibrils shows the widespread and complete infantile condition
of the neurons, and this under-development of fibres, though secondary to
the cellular condition, may in part account for the position which the
cells retain, since thick healthy fibres would necessarily tend to displace
cell structures in the sub-cortical regions. It is, I think, clear that this
case should be put in a different category from those in which isolated
areas appear in the walls of the ventricle; the occurrence of the latter
in otherwise normal brains shows that, though they may be develop¬
mental anomalies, possibly reduplication of lenticular, caudate, or
amygdaloid nuclei, which we know to be of similar origin to the cortex,
there may be no marked under-development of neurons in these cases
and they are not necessarily accompanied by epilepsy or deficient mental
capacity.

RKFKHKNC’KS.

Anton. “ Handbuch der Pathologischen Anatomie des Nervensysteiiis,” vol. i., lb 429.

Meine. Kill Beitrag ziir Lehre von dor echten Heterotopie graiier Kirii8ul)staiiz,’’
Archiv. f iir 1897.

Kolschitkowa. “ Beitnige zur Pathologischen Anatomie der Mikrogyria und der
Mikrocephalie. (Aus dem Lab. in Zurich).

Yikchow. “Heterotopie der gnuien Hirnsubstanz,” Virrhoiv 8 Archiv.^ Bd. 38 8. 138.

Mierzejkwski. “Research in Idiocy.” Reported by Take. J. M. Sc., 1879.

Matell. “ Kin Fall von Heterotopie der grauen Hirnsubstanz in den beiden Hemis-
pharen des Grosshirns,” Archiv. far Psych., Bd. 2o.

Tede.s( HI. ‘ Heterotopie der grauen Hirnsubstanz bei einer epiliptischen Idiotin,”
Virclunr'ii Archiv., Hd. Ib9.

Herxheimek uud (iiEKLlcii. Studicu iiber di(‘ Ncuirolibrillrui ira Gentralnerven-
system.” (Wiesl)ad(ui, 1907, Bergniann.)

A PRELIMINARY NOTE ON BRAIN WEIGHTS AND MEASURE¬
MENTS IN THE INSANE.

By Hklkn G. Stewart. M.D.

The relation of normal brain weight to body weight was worked out
by Mai’shall from data collected by R. Boyd, and eiforts have been made
at various times to correlate brain weight and mental deficiency or
mental perversion. The indifferent success of these efforts is not a
matter for wonder w hen we consider the various factors which may con¬
tribute to alter the relative brain weight apart from the normal develop¬
ment of nerve cells and fibres. Nevertheless the low' type of some of the
brains seen at asylum ijost-mortenis is a striking feature and is not
confined to a low weight us compared with the body w'eight. In the
following iiHjnirv, w’liich was suggested by Dr. Mott, the relation of the
weight of tlie cerebral liemispheres to that of the combined pons, medull i,
and cerebellum (normally 8 to 1) has been considered as w'ell as several
other factors.

In all, the results of the notes in 1(57 cases have been analysed, and
the features which have been taken as indicating a congenitally low
type of brain or an unequal development predisposing to insanity are: —
(i.) A brain weight markedly below the average healthy weight for
the same age, body weight, and height. For this purpose the weight of
the whole brain was taken, together with the membranes in situ,

(ii.) A disproportionately low weight of cerebrum as compared with
the united weight of pons, medulla and cerebellum. In this case the
loss of w^eight from wasting, as evidenced by thickening of the mem¬
branes and excess of cerebrospinal fluid was taken into consideration.

(iii.) A poor development of the higher (association) areas, as shown
by: —

(f?) Shallowness of the fissures.

(6) Poverty of secondary markings on the convolutions.

(c) Flattening and poor development (and therefore diminished
size to measurement) of lobules, especially in the frontal and parietal
areas.

(d) The extension of some areas beyond their normal position, e.g.^
the extension of the striate area on to the parietal surface as indi¬
cating a measure of poor parietal development.

A brain tissue has been considered to be of low type if the condition
in (iii.) co-exists with either (i.) or (ii.). If the features given in (iii.)

298

AKCHIVES

occur alone the brain has been considered low type. Working on
this basis it was found that 32 in 84, or 39‘2 per cent., of the male
brains were of undoubted low type, while 11 in 84, or 13* per cent, were
of ? low type. In female brains 28 in 82, or 34*1 per cent., were of low
type, and 16 in 84, or 19*5 per cent, of t low type. Thus, taking male
and female together, 30*65 per cent, of the certified insane dying at
Claybury possessed brains of a low type, and if to this number the 16
per cent. ? low type be added, the percentage amounts to 52*3 of the
total insane.*

In this connection, it is interesting to note that of four cases of
tumour of the brain three show the conditions mentioned in paragraph
(iii.), and in the fourth case no particulars were given. Since in a
normal brain the occurrence of a cerebral tumour causes certain definite
symptoms, while in cases of tumour of the brain which are admitted to
asylums insanity is often the only prominent feature, it seems probable
that in the latter cases the brain is inherently liable to insanity, and
any disturbance of the normal equilibrium is sufficient to cause the onset
of symptoms. In the three cases mentioned above tlie tumours differed
greatly in position and size. One, occurring in the calamus scriptorius
of the fourth ventricle, measured 2 cm. in length; a second was in the
region of the pituitary body, and had a diameter of about 4 cm.; the
third occupied the left frontal lobe, and extended from the anterior pole
of the hemisphere to the level of the anterior liorn of the lateral
ventricle. Thus it appears that the factor causing insanity in these
cases is neither the position nor the size of the tumour, but is, probably,
a condition common to all three of the brains mentioned, /.r., a low type
of development— as an inherent defect.

The following tables show the relation of the weights of the “ insane ’’
brain—of ordinary type and low type ” respectively—to those of the
brains of healthy persons of the same age and height. The tables for
normal brains are taken from Quain’s “ Anatomy of the Brain.” In the
case of the figures bracketed only one brain of that age and height
occurred in that class, hence no conclusion can be drawn. These figures
show clearly that brains possessing the features mentioned in paragraph
fiii.), and called ‘Mow type,” have a lower average weight for the same
height and age than brains of either the rest of the insane or the healthy
type.

* Sin(.>c ficcurato mc.isiiremcnts have taken in all brains ( 7 *.<*., the last 46 cases con-

side-ed alM:)ve) Mie pprcenta^R has been found to be considembly hipher. In the males, 10 in 21,
or 4S per cent., were low tyne, and 4 in 21. or 18 per cent., of ? low type. Among the females,
14 in or r>r> per rent., were low type, and 6 in 2''. or 24 per cent., of ? low type. If these
figures be taken together it gives 80 per cent, females and 66 per cent, males of a low type, or a
total of 73 per cent.

BRAIN WRIGHTS AND MEASUREMENTS

299

Tables.

Avenij^e relation of Brain weights of Sane and Insane of normal and low type,
arranged according to age and height.

FEMALE BRAINS (82 Cases).

1.-

Sane (Quain's “

Anatomy ”).

20-40 Yrs.

40-70 Yks.

70-90 Yrs.

I’h2 metres

and over

1245

1209

1166

IW „

to 1*62 metres

1218

1211

1129

I-5-2 „

and under

1198

1204

1112

11.—Insane (not low type).

20-40 Yrs.

40-70 Yrs.

70-90 Yrs.

1*62 meties

and over

1268

1221

1160

1-54

to 1*62 metres

i:i25

. 1213

1100

1*52 „

and under

—

. 1272

—

111.—Insane (low type).

20-40 Yrs.

40-70 Yrs.

70-90 Yrs.

1*62 metres and over

1163

. 1168

1191

to 1*62 metres

1125

1177

1056

1-.52 „

and under

(1-260)

. 1J27

(^70)

MALES (84 Cases).
I.— Sane.

20-40 Yrs.

40-70 Yrs.

70-90 Yrs.

1*72

metres and over

I4im

1364

1329

1 67

to 1*72 metres

1360

1334

1304

1*65

„ and under

1331

1296

1251

11

.—Insane (not low type).

20-40 Yrs.

40-70 Yrs.

70-90 Yr.s.

1*72

metres and over

1466

1371

1322

1*67

„ to 1*72 metres

1297

1376

(1400)

1*65

„ and under

(1080)

1309

1267

III.—Insane (low type).

20—k) Yrs.

•Ki-70 Yrs.

70-90 Yrs.

1*72

metres and over ...

1357

1321

1117

1*67

„ to 1*72 metres

1186

. (10.^7) ...

(1062)

1*65

„ and under

1199

—

—

Nevertheless, it is not contended that all, or even any, of the features
mentioned above, are peculiar to the brains of the insane. Many of the
patients were not imbecile, and hence sane in the eyes of the law until
their certification at various ages. Therefore, we must believe that
numerous brains of this type do not enter asylums, and are to be found
in the P. M. room of any hospital. But the large proportion of brains
with features indicating a low type of development among asylum
patients suggests that such individuals are more subject to a disturbance
of the mental equilibrium than members of the community who possess
brains of the average type.

800

SOME OBSERVATIONS ON A CASE WITH IMPULSIVE
OBSESSIONS OF SUICIDE AND AUTO-MUTILATION.

By henry DEVINE, M.B., B.S. (Lond.), M.R.O.P., Assistant Medical Officer,
Loudon (-oiinty Asylum, Loii>^ Grove.

Though the literature in connection with abnormal impulsions is
already so extensive, the following case seems worthy of record, as it
presents several features of interest.

The psychological mechanism which produces such striking modifica¬
tion of the fundamental human instincts, as impulses to suicide and
self-mutilation, is oiten extremely complex and difficult to interpret. In
one group of cases they are manifestly secondary to an insane mental
state, of which, indeed, they are only the logical outcome. Under this
category come states of depression or some form of hallucinosis, where
the sensory promptings are often endowed with strong impulsive force.
In another group the impulse is carried into execution in a state of more
or less unconsciousness, with subsequent amnesia. The impulsions of
epilepsy, acute alcoholism and hysteria are frequently of this type. The
, origin of the impulsions becomes nuich more obscure when they form the
most obvious feature of the psychosis and are carried out in a state of
complete consciousness, with the intellect unimpaired and the patient
recognising the irrational character of his actions.

There are no general principles which adequately explain all the cases
comprised in this group, and, indeed, the impulsions would sometimes
seem to result from some unknown perversion of the normal instinct of
self-preservation.

Mrs. W. was transferrc'd to the Long Grovo Asylum on October 28th, 1907,
having been originally certified in January, 1902. Her age is 55. She is of
medium build and weight. Some slight facial asymmetry is noticeable, and the
palpebral fissures slope slightly upwards and outwards. These features give the
expression a somewhat unpleasant cast. Physical examination reveals signs of
mitral and aortic disease and thickening of the right pleura. These lesions are
well compensated and she is otherwise strong and in moderate health. As regards
her general mental characteristics she is a quiet, reticent and somewhat self-
engrossed woman. She is not, however, actually unsociable, and she establishes
herself on terms of friendship with some of her fellow patients. She is, however,

OBSESSIONS OF SUICIDE AND AUTO-MI TILATION 301

sensitive and easily upset, but shows very little outward signs of such feelings,
becoming, when in any way annoyed, quieter and more reticent. She is very
industrious and obliging, 'ihe intelligence is about the average, and there is no
evidence of any delusional ideas. Owing to the fact that she looks on herself
as an undesirable member of her family, she has for many years ceased all com-
munication with them. Her memory is, however, ready and faithful, so that
although the history which follows is mainly a personal one, there is no reason
to doubt its accuracy. Any of her statements which it has been possible to verify
from independent sources coincide identically with her own.

The family hUtory is as follows : As far as she knows the grandparents on the
mother’s side died of senility and showed no neuropathic tendencies. On her
father’s side she knows nothing ol tiiein; one of his sisters died of phthisis and
the other went to Australia and has not been heard of since. Her father himself
was extremely passionate and gave way to bouts of excessive drinking. Her mother
committed suicide, as also did one of her sisters. Her two other aunts were
apparently normal mentally.

The children of this union were nine in number. The patient herself is the
fifth child and has strong suicidal tendencies. Her younger brother committed
suicide for some trivial reason; one sister was hysterical. The other children dis¬
played no abnormal tendencies, two dying of fever in adolescence.

In spite of many gaps and imperfections in this history, it is of con¬
siderable interest, for we find an alcoholic father (? dipsomania) and
three suicides in the two generations with a potential case in the patient
herself. She has not seen her relatives for some years, and it is quite
possible that there may now be further manifestations of this neuropathic
heredity. Unfortunately this cannot be investigated. The incidence of
suicides is especially noteworthy. Heredity seems to exercise a particu¬
larly strong influence in the production of this particular impulsion, and
numerous remarkable examples are recorded. Bucknill and Tuke quote
a case of Falret's, where four brothers in a family of six attempted
suicide (1). Two of them, in addition to a cousin, accomplished the act.
Morel mentions an instance where seven brothers destroyed themselves,
though in good position and suft'ering from no misfortune (2). In these
cases, no doubt, imitation and suggestion play a large part. Analogous
are instances of collective suicides and suicide a deux. These factors are,
however, probably only operative given a primary neuropathic predis¬
position.

In his presidential address at Leicester, in 1905, Dr. Mott gives a
striking instance of four generations of suicide (14). The result of
imitative suggestion on a neuropathic stock is in this case especially well
illustrated, for one sees that precisely the same method of accomplishing
the suicidal act was adopted in three consecutive instances.

302

AKCHlVtS

This will be clear from Dr. Mott’s diagram: —

Admitted to Cane Hill
for attempted suicide
by poison.
Patiknt IV.

An epileptic. Attempted suicide j |

in 1874 by cutting her left arm. Mother III. Father sane.

Was taken to Colne}- Hatch, i

where she still remains.

Committed suicide by ] j

cutting his left arm, Father II. Mother, died insane.

and dying from (

haemorrhage. i ^ ^ "

4 children, 3 males and 1
female. All confined in
lunatic asylums.

_Mother, died insane.

Father 1. Mother committed suicide.

(Jut her left arm, and died
from hfiemorrhage.

The early history of Mrs. W. is as follows: —

Up to the age of nine her life was uneventful. She was delicate, and her
education was somewhat deficient for that reason. At this period her aunt paid
a visit to her mother and told her that slie had been su^ering very much from

pains in the head, adding “I don’t expect you will ever see me again.” The

next day the news came that she had committed suicide by taking poison. The
information impressed the patient curiously. Instead of feeling very shocked, she
thought what a pleasant form of death it was, and how nice it would be to die
in a similar way.

From this notion she was unable to rid herself. It became a veritable obsession,
and made her life very miserable. The idea shortly afterwards acquired impul¬
sive force and she swallowed some white precipitate. Prompt treatment averted
serious consequences. Not long after she was discovered by her mother kneeling
down by the bed, holding an open razor and praying that she might have strength
to destroy herself. She had already inflicted a slight cut. At the age of 14 she
was sent to service. One day, while cleaning a grate, she suddenly threw down

the brushes, rushed across the road and jumped into the sea. This, she says,

was quite a sudden and unpremeditated impulse, and is quite inexplicable to her.
She was rescued and sent to a “ home of correction ” for 12 months. Upon her
release the same feelings and ideas ob.sessed her. She became restless and uneasy,
and was unable to settle to anything. Having obtained some laudanum she was
again nearly successful in taking her life. On this occasion the doctors said she
had swallowed enough to “kill a horse.”

01iSi:SS10i\S Oi' JiUlClDE AND alto-mutilation

More or less serious attempts at suicide in children are not uncommon.
Janet mentions several cases, one in a girl eight years old For thre^
years she had only had one idea in her head—that of dying. Slie was
constantly talking about it and made various preparations for carrying
her ideas into execution. The origin of the obsession was quite obscure.
In other cases described some trivial motive provoked the act—punish¬
ment for a fault or some trifling humiliation. Such a reaction is, how¬
ever, always indicative of profound nervous instability, usually here¬
ditary. In the present instance the origin of the idea is more or less
evident, dating, as it did, from her aunt’s suicide.

At the early age of 10 she married, and for many years lived more or less
happily. She had no family. She was still, however, convincetl tliat slie was
fated to die by her own hands and was constantly obsessed by the desire to accom
plish the act.

These feelings w’ere always aggravated by any trifling upset, and then the impulse
was with difliculty controlled. JShe describes how sometimes slie would walk
for miles to remove herself from temptation, often, however, going so far as to
purchase poison tSometimes there st?em to have been actual attempts, but none
very serious. 8he remarks that it is a mystery to herself why she never succeeded.

The last few years of her married life were unhappy ones; her husband was
intemperate and treated her badly. At the age of 40 she was going to Brighton

with her husband on a visit to her mother; on the way he told her not to be sur¬
prised if she found her mother was dead. Upon her arrival she discovered that her

mother had recently cut her ihroat and that a few months previously her brother

had hanged himself. No cause was assigned for the mother’s action, and her
brother had apparently had some difference with his wife. This news seems to
have reduced her lo a state of desperation, and she felt indifferent to anything
which might happen. She confesses to some excess in alcohol and that she quarrelletl
fiercely with her husband. Shortly aftenvards she sc*t fire to their house and
delivered herself up to the police, telling them that her intention was to destroy
her husband. She now says, however, that she was in a state of frenzy and did
not really appreciate what she was doing. She was sentenced to 12 months’ im¬
prisonment for arson ; while in prison she tried to starve herself and was reduced
to a state of emaciation. Upon her release she went to live with a brother and
separated hersidf from her husband. Eventually she obtained employment in an
hotel. She mentions one or two occasions during this period when she purchased
poison with suicidal intentions. In January, 1902, she went to the Infirmary
suffering from tonsilitis, and was transferred from there to the Cane Hill Asylum,
the certificate stating that she was depressed and threatening suicide.

T)r. ^londv has very kindly furnished details of her conduct in the
asyluni. Tlie following are the salient features: —

She was very depressed on admission and remorseful over “ acts she can never
undo.” She was morose and reticent, and usually sleeph*ss, but had much im¬
proved by May of the same year, when she again relapsed, refused her food and

304

AECHIVES

had to be fed mechanically. She heard voices telling her to die, and she had
marked ideas of unworthiness. During the year she had frequent relapses of this
kind, in the interval, however, giving no trouble and working industriously. In
May, 1902, she smashed three windows without any warning, explaining subse
quently that the “devil was inside her’* and she “wanted to see the blood fly.”
From this date she was subject to paroxysms of impulsiveness, and frequently
inflicted more or less serious injuries on herself. She was transferred to Hellingly
on March 18th, 1904.

The following particulars of the patient were kindly supplied by
Dr. Taylor, the Superintendent of Hellingly Asylum: —

On admission she is described as being dull and perplexed, constantly rubbing
and looking at her hands, and only expressing herself in a disconnected way. “ 1
am quite w'ell and not afraid; smashed 15 windows in Cane Hill; I liked to be
covered with blood sometimes. It isn’t that I hated the place. I*ve never been
the same since poor mother died; she killed herself; cut her head off; did it with
a razor. They all die like that. 1 never should, though; l*m too big a coward.
I like myself too much for that.”

She soon improved, though frequently irritable and bad tempered, but showed
from time to time extreme impulsiveness. An eye-witness describes how she would
suddenly jump up and either smash windows or crockery, explaining that she
liked to feel “wet blood.” Towards the latter part of her time in the asylum
she became more cheerful and less impulsive, and was transferred to the Long
Grove Asylum on October 28fh, 1907.

Since her transfer the following parti(‘ulars have been noted: —

During the time she has been under personal observation there have been no
severe impulsive outbursts, though she still has similar tendencies which are
fortunately less serious in their consequences. There have been no attempts at

suicide, though she still retains a fatalistic belief that she will die by her owai

hands. The most obvious abnormality which she exhibits is a craving to inflict
wounds upon herself. As she shows more or less anxiety for discharge, slie makes
a superficial attemiit to conceal her strange prut>t*nsity and frequently says : But
I’m all right now ; jierhaps I may never waJit to do anything like that again. 1
am quite able to go right aw’ay.” She cannot, however, hide the fact that she
has a constant craving for the sight of her own blood. Though she tries to make
light of it and adopts a callous lone when talking on the subject, she quite realizes
that such a craving is unnatural and abnormal, and adopts various precautions
against yielding to the impulse. Thus she sits in a remote corner of the room

as far away from the windows as possible, bc^causc they are such a source of

temptation to her. They sometimes arouse in her such an irresistible impulsion
to smash, that sht‘ is forced to walk aw^ay from tlu'm or cover up her eyes with her
cjpron. She finds that constant (*rnploynient is the best means of diverting her
atUmtion from the craving, and alw'ays oceiipies herself most industriously.

Periodical states of depression are noticeable, when she becomes rather irritable
and more reticent. At tlu*se times she broods over former acts of delinquency and
thinks how wicked she has Tiife becomes almost intolerable to her, and she

OllSKSSIONS OF srU’lOK AND Al ro-MOTlLATlOX

fi'els tliilt the I'oiiliiu* of in r clail^ oxistoiice caiiiiot be endured any long(‘r. The
craving ti> wuiuid herself, at sucli times, becomes an imperative necessity. Her
sleep becomes disluibed, and if she should drop oft for a few minutes she has
unplcisant dreams in which she pictures lierself smashing and cuveix*d with bloc>d.*
Having at length yielded to llie impulst^f, these depressing feelings vanish and
she exi)eriences a sense of great relief.

Ihis secpieiice r{ events has ocMirred several times while she has been under
(•bservation. Lsually she is content with inflicting trivial abrasions on her skin,
hlie tries to conceal them, but does not deny that they were purposely produced
when lliey are discovered. She generally tries to turn the subject or smiles and
says: “Oh, that’s nothing. I feel better now. It’s nothing to what I used to
do I ” On one occasion she pieked up a bit of glass and inflicted a more severe
gash on her arm. She was very upset when tlie incident was reported to me,
and was unwilling to have the arm examined. Eventually she confessed that
someone had spokcm unkindly to her and this liad produced feelings of depression.
She had discovered the glass accidentally and had immediately sought relief bv
cutting lierself.

Her more general mental state has already been described.

The above history reveals the fact that for many yeais the act of
suicide and latterly stdf-mutilation luive possessed for Mrs. W. a peculiar
at traction.

Though site tries to restrain these strange cravings, knows they aiv*
ahnorimil, and adopts various precautions against carrying them into
execution, yet she makes it clear that the ideas in themselves are not
repugnant to her, and tliat she has always experienced gratification and
relief when she has to some extent yielded to them.

The question which arises is, what signiticance must be attached to
such evident moral peiwersion as the patient displays!*^ Uo these un¬
natural cravings indicate that the patient has iiilierited tendencies which
are fundamental and instinctive in her though repugnant to the instincts
of the normal individual ? Her general mental attitude towards these
ideas, and the fact that she developed suicidal tendencies while very
young, seems to almost indicate that such is the case.

An endeavour will be made to show, liowever, that her cravings are
purely accidental in origin and imply no original and inherent moral
defect, differing only from the ordinary harmless obsessions in their
particularly unpleasant content and the impulsive force with which they
are at times endowed.

* This is an interesting example of a dream mechanism liesfiihctl by Freud in his
“ Traumdeutung” (4). In the waking state we have a conflict of two systems of emotionally
toned ideas or, as they are t(‘rmed, *• complexes.” In the present case these are the obsessive
impulse to draw blocKl, and the total system of motives and ideas of the personality whirh
endeavours to repress this desire. During sleep the j^ersonality loses its co-ordinating force and
the suppressed complexes tend to run riot. Hence it is common in dreams to find the suppressed
desired fulfilling themselves. This has occun*ed in the present case. It is more usual, howevet,
for the complex to express itself symbolically rather than directly. {Sre oho Jung (4).)

U

Ill the first place it is easy to deiiioustrate that the instinct of self-
preservation is as strong in iirs. W. as any one else.

When she suffers from cardiac pain or has some oedema of the feet
owing to her heart lesion, she is very worried and grieved, willingly
taking any advice which may be given to promote her recovery.

It is evident, therefore, that she does not really want to die or sailer
pain more than any one else, though, at the same time she will say that
the idea of suicide is neither repugnant nor unpleasant to her.

Again, though obsessed for many years by the craving to take her
own life she has never succeeded in completely accomplishing the act.
Many writers have noticed that suicidal obsessions are usually more
theoretical than impulsive. Tlie qucvstion is a large one, and is fully
discussed in Janet’s “Obsessions” (6). Though in the present case the
patient’s impulses have been numerous and serious in tlieii* results, yet it
is extremely significant that slie has never actually gone so far as to take
her own life. Apart from other consideiations which might be discussed
in regaid to this point, one is justified iu assuming that the instinct of
self-j)re.servatiou has been sufficiently strong to prevent her from com¬
pletely yielding to the imjjulse which is so imperative. As she herself
says: “ I am too much of a coward. I’m too fond of life.”

Paradoxical as such a state of mind appears to be, it seems as if it
is not so much a wish to die wliich has obsessed her but the particular
act of suicide, wliicli exercises such a peculiar fascination.

The condition is analogous to that of the dipsomaniac, who has no
wish to become drunk, but has acquired a tendency which he is unable
to resist and which at times becomes an imperative necessity of his
existence.

This curious attitude is well shown by her statements in regard to one
of the occasions when she was trying to starve herself. She said that
tliough the pangs of hunger were very severe tliey were far outweighed by
the pleasure she experienced at yielding to her craving for suicide.

It is now necessary to notice more particularly the conditions under
which tlie suicidal obsession originated.

How far external events which produce a strong emotional reaction
are instrumental in the production of fixed ideas is a matter of consider¬
able dispute. Even those writers who consider that psychic trauma is
the necessary antecedent of an obsession demonstrate that the fixed idea
itself is not usually the original idea associated with the painful emotion,
but one wdiieli is substituted for it. The emotion remains unchanged
and attaches itself to an apparently irnJevant (defensive) idea which
constitutes the obsession (7).

In this particular case, however, not only is one justified in assuming

OnSKSSIDNS OF srU’lDK AND A I To-M I TIL \T1( »N

tiOT

thnt the obsession owed its origin to a very definite moral shoek (news
of her aunt's death) wliieli the patient experienced, but also it is to be
noticed that the content of the obsessions is immediately related to the
event which provoked it.

Such an obsession is called by Freud “ traumatic,” and is distin¬
guished by him as a class apart from the usual type. He says it is an
intense obsession \vhich is nothing else than the memories—the unaltered
images of important events (8).

Janet also mentions that it is possible for some isolated moral shock
to determine the origin of an obsession and its peculiar content (9).

Kratft Kbing may also be quoted when he says: “A fixed idea may
come into consciousness suddenly or is called up by some violent external
event (suicide of friend). The content in the latter case (/.c., perceptual)
consists of the continued activity of apperception with reference to the
original distressing thought’’ (10).

It will be remembered that when the patient was informed of the
tragic death of her aunt she re-acted very abnormally. The most
natural and adequate reaction would have been the ordinary manifesta¬
tion of grief in a child, viz., a fit of crying.

If this had occurred the emotion would liave been ‘'worked out’’ and
the ideas bereft of tlieir affect w’ould have been forgotten in the process of
time.

Instead of tliis a very different sequence of events occurred. Among
other painful associations aroused was a not unpleasant one that such a
death was easy and attractive. Such an idea might, of course, occur to
anj^ one and in itself implies no defect of moral sense. The abnormality
lies in the fact that it assumed a pathogenic character and remained as an
insistent obsession. The explanation of this may be that the idea was
here a " defensive ’’ one, and remained fixed by the emotion which failed
to find expression in tlie ordinary way.* Whatever be the exact
mechanism of its occurrence it is clear that from this time, as she herself
says, she could not rid herself of the idea of suicide and henceforth
became miserable, depressed and morose from the craving to follow her
aunt’s example.

This obsession has now become to tlie patient no more than a theo¬
retical belief that she will die by her own hands, as so many of her
family have done. It has been replaced by a craving to wound herself.
When she smashes ” she says she has no idea of taking her own life

* The word ‘‘defensive ” iP here used in the sense that the idea was effective in protecting
the personality against the ])ainful complex which must be* aroused by a moral shock such as
the patient experienced. This complex was “ 8uppres€ed ” by the protective idea instead of
being normally expressed by the usual emotional outbursts.

AUClllVES

aoS

and ntdtlier does she wisli to needlessly destroy the property of the
institution. Being a well-disposed wojnan she regrets giving trouble,
but says she really cannot lielp herself from smashing at times, because
she craves so much to see the blood flowing from the wounds which she
inflicts.

Tlie craving arose quite accidentally. She was at Cane Hill at the
lime passing through a phase of considerable depression. Shortly before
she had been fed mechanically c»wing to refusal of food. She had become
obsessed by ideas as to her own wickedness and felt quite unable to shake
off her depressing tlioughts; existence became so unbearable to her that
she felt the iinperative necessity of doing something desperate to “ relieve
her feelings.’’ She savs she seemed to be “ dominated bv the devil ” and
something inside her appeared to be telling her to smash. (These sensory
disturbances probably come under the category of pseudo hallucinations.
They did not have for her the attribute of objective reality and would
seem to be the symbolic expressions of her compulsive feelings.)

In this state of mind she suddenly and for the iirst time smashed
several panes of glass, inflict iiig several cuts on her arm ; this was success¬
ful in relieving her depression and she experienced a feeling of relief
and satisfaction. The patient's action is quite comprehensible, and one
finds aJialogous examples in normal life where persons attempt to suppress
painful feelings by violent and sometimes irrational methods of distrac¬
tion. The interesting feature is that from this time the craving to wound
herself commenced to obsess her. She knows her craving is absurd and
frrational, yet at times it becomes irresistible. What had happened is,
cliat the painful complex of uiiworthiness had been suppressed by this
unnatural impulse, which thus became an act of defence against the ideas
whieli caused her so much anguisii.

This particular mechanism in the origin of impulsions is described
by Freud in the following words (11): “ The primary idea .... is
replaced by acts or impulsions which have served originally as methods
of relief or protection, and which now find themselves in grotesque asso¬
ciation with an emotive state which does not belong to them, but which
has remained unaltered.’' An illustiative example may be quoted:
“ Obsession of arithmonomania.—A woman has contracted the habit of
always counting the hoards of the floor, the steps of the staircase, etc.,
which she does in a state of absurd distress. She had commenced to count
to distract herself fi’om the obsessing ideas (of iemptation). In that slie
was successful, but tlie obsession to count has taken the place of the
(uigiiial obs(‘ssion.”

In a paper on impulsion'^, some of which closely correspond to those
observed in ilrs. W., Janet gives a somewhat similar explanation as to

OnSKSSlONS OF sriClDE AND AI TO-M FTILATU)N

ao9

tlieir partitular rule in relieving tlie crisis oi psycliastlieiiia (12). He
says: “ These absurd acts are passionately sought for simply because they
are exciting acts, and these individuals have an urgent need of excitation
on account of the anguish wiiicli tlie mental depression produces.” This
point of view is well illustrated by tlie present ease. It will be remem¬
bered that the patient from time to time became veiy depressed and
miserable. She felt unable to concentrate her attention on anything,
realised the hopelessness of her position, and became generally irritable
and out of touch with her environment. Sometimes these crises appeared
to be due to some exciting cause, e.//., a slight rebufl: or the death of a
fellow patient to whom she was attached. The latter incident produced
a very marked psychasthenic state. She was obsessed by ideas that
she must be diiferent from everyone else, and that anyone who came
into contact with her seemed to be dogged by misfortune and trouble,
etc. At other times these crises appeared for no apparent external cause.
It was always on such occasions that tlie craving became uncontrollable
and she felt the imperative necessity for wounding herself.

Thus far an attempt has been made to show that the unnatural
impulses displayed by Mrs. W. were not instinctive in her, but were
accidental in origin, the result of certain emotional experiences.

Seeing that suicide was relatively common in her family the question
arises as to what part this neuropathic tendency played in the production
of a similar impulsion in the patient herself. The answer seems to be
that the suicidal impulse was transmitted in the same way as one sees
alcoholism occurring in successive generations of the same family. Bevan
Lewis (13) has recently pointed out in a paper on the subject that in no
sense can alcoholism be spoken of as inheritable, i.e., alcoholism as a
specific character.

He says “what is transmitted by an alcoholic ancestry is a defective
organisation of the neuron, revealing itself in a loss or weakening of that
primary attribute so characteristic of nervous mechanism—inhibition.”
Such an obsers^ation applies equally well to the case of Mrs. W. One sees
a very striking example of a bilateral neuropathic heredity in the produc¬
tion of a congenitally weak mental organisation.

The hereditary instability is the condition which has been transmited.
It finds expression in abnormal modes of reaction in times of stress, the
occurrence of unnatural cravings and obsessions, periodical crises of
dejmession, and states of defective inhibition. The peculiar content of
the obsessions must be ascribed to the nature of the event which has
provoked it. Education, environment and psychic trauma, espe<‘ially in
the suggestible period of early life, may either modify or produc(^
abnormal mental tendencies, but one must assume that, fiom the first, in

AKCHIVKS

aio

that class ot case coming under the general category of “ psychic
degeneration ’’ there exists a badly endowed nervous organisation which
forms the soil for the development of the various types of neurosis.

What specific causes make one individual an hysteric, another a
paranoiac, and another a psycdiastheuic are at present imperfectly
understood.

In conclusion, I must express my indebtedness to Dr. Bond for per¬
mission to publish this case, and also for his assistance both in obtaining
facts as to her previous history and in making suggestions in regard to
some of the points of interest.

REFERENCES.

(1) Bi ckxill and Tuke. “ Psychological Medicine. 18.^8, p. JOH.

(2) Morel. “ Traite de Maladies Mentales.” 1800, p. KU.

(13) Janet. “ N^vroses et Idees Fixes.’* Vol. ii., 1898, p. 188.

(4) Freud. “ Die Traumdeutung.”

(5) Jung. “ Uber die Psychologie der Dementia Pnecox.” 1907, p. <j2.

(d), (9) Janet. “ Le.s obsessions et la psychasthenie.” \"ol. i., 19o:).

(7), (8), (11) Freud. “ Obses.sions et Phobies,” “Revue Neurologique.” Yol. iii., 18!C).
(10) Krafkt Ebing. “ Lehrbuch der Psychiatrie.” 190o.

(12) “The Pathogenesis of some Impulsions.” Joiirmil o/ Ahuipntuvl J^tnjch, April,

1900.

(13) Bevan Lewis. “Alcoholism, Crime and Insanity.” Jouni^il of Menial Srienvk'.

April, 1906.

(14) Mott. “The Relationship of Heredity to Disease.” Brilish Medical Journal.

October 28th, 1905.

311

A SHOUT AO(!OUXT OF THE INCIDENCE OF DYSENTEUY
AT LONG GROVE ASYLUM FEOM ITS OPENING
(JUNE I8th, I'JOT), TO OCTOBER 3Ist, 1908.

Bv GKOFFUEY CLARKE, M.D. (Lond.), Second Assistant Medical Officer.

Much has beeu written during recent years, both in these arcliives
and elsewhere, on “ asylum colitis,” or dysentery, and there appears
but little excuse for increasing the literature upon the subject, save from
one who can throw further light upon the aetiology of the disease in its
widely different forms.

No such work has been done on this disease at Long Gh*ove, but we
have unfortunately been favoured with a very large number of cases,
and as a careful record has been kept of these from the opening of the
institution, Dr. Mott suggested that a summary of our cases, their ward-
to-ward transfers, with a few notes and observations on our experiences,
might be of value.

There is now but little room to doubt that asylum dysentery is one
of the infective diseases caused by a specific organism, the isolation of
which appears to be very difficult, and bacteriologists are not yet agreed
as to its exact nature.

Our ignorance of the life history of the organism causing the disease
adds greatly to the difficulty of efficient disinfection, isolation, treat¬
ment, &c. The incubation period of the disease, why or by what conjunc¬
tion of circumstances it appears in such widely differing clinical forms,
whether the stools alone are infective, and the duration of infcctivity after
the disappearance of symptoms, are questions which still await definite
answers.

The period with which this paper deals extends from the opening
of the Asylum, June 18th, 1907, to the end of October, 1908, during
which time over 2,500 cases were admitted. The great majority of the
early admissions were transfers from other asylums, and most of them
had been insane for many years. In cases of all transfers enquiry forms
were sent, asking (amongst other questions), whether the patients, dur¬
ing their sojourn at the asylum, had had any diarrhoecal or dysenteric
attacks, so that we had some record of all our transferred patients in
this respect. But, as the Tables at the end of this paper show, in only

m

AKCIIIVKS

one case was tlieie a record of previous dysentery and one of simple
diarrhoea/^

The method adopted in dealing with the disease has been uniform
throughout; that is, immediate isolation of all suspicious cases, disin¬
fection of all clotliing, &c., with whicli the patient had come into contact,
and nursing and sanitary precautions, as in eases of enteric fever. It
is interesting here to note that during the period under discussion three
cases of enteric fever have occurred. One evidently contracted his in¬
fection prior to admission, and in the other two no source of infection
could be ascertained, but tliey occurred in different parts of the asylum
and at considerable intervals. The diagnosis in each case was confirmed
by the Widal reaction : two proved fatal and the third was subsequently
discharged recovered. In none of these cases did the disease spread,
but, during the same period, although similar precautions have been
taken, we have had 80 cases of dysentery. On the male side all sus¬
picious cases were isolated in J.l infirmary until the opening of the sana¬
torium in June, 1908, as a dysentery villa; on the female side F.l in¬
firmary has been used throughout.

Typical and severe cases of dysentery are easily recognised, but even
here some time must often elapse before a certain diagnosis can be
arrives! at, as the general symptoms of an acute infective disorder often
precede those pointing to disease of the bowel by a considerable number
of hours; indeed, it is no uncommon occurrence for a patient to complain
of constipation at the commencement of the attack. A large preliminary
dose of castor-oil is helpful both as a method of diagnosis and treatment.

The mild, atypical, and abortive cases are very difficult to discover,
and there is not the least doubt that many of tlicm are reported as cases
of simple diarrhoea, and probably as many more are never discovered at
all and get well without any form of treatment. Several of our cases
ere discovered quite accidentally. Two of them were patients who slept
in single rooms and the diagnosis was made by the discovery of blood
and mucus in tlie chambers which they used. These two patients made
no complaint, there were no constitutional symptoms, the motions were
not frequent, and, after being transferred to the isolation ward, no fur¬
ther abnormal motions were passed. Had the.se patients been sleeping
in a dormitory and had access to a water-closet instead of being obliged
to use their chambers, it is probable their attacks would have passed
unnoticed. In another case, a sensible patient, whose statement might
be relied upon, complained to the doctor that, instead of the constipa¬
tion with which he was usually troubled, lie had for the last few days
suffered from diarrhcea, and liis motions contained blood. The next
motion was saved, and was diagnostic of dysiuiterv; the patient had a

DYSEXTKRY AT LONG GROVK ASYU M

e3i;]

somewhat severe attack, but much resented being sent to bed and placed
on milk diet. This patient worked in the ward, and, both inside and
out, had free access to the lavatories, and he had not complained to, or
attracted the attention of tlie attendants.

Another patient stated that on several occasioiis during the last five
years he had passed blood and slime for a day or two at a time: the first
occasion being whilst ho was an inmate of a large workhouse infirmary.
He had not thouglil it worth while complaining to a doctor, more parti¬
cularly as he disliked being transferred to an infirmary ward and going
to bed. There seems no reason for doubting the truth of his story, and he
had probably previously had several mild atypical attacks of dysentery.

The main building of the asylum consists of two stories. The wards
are designated by letters: the ground floor being called “one,'' and the
first floor two.” Thus, A.l is on the ground floor, and A.2 directly
above it. llesides the main building, which contains between l,(i00 and
1,700 patients, there are eight villas, accommodating 400 patients.

A glance at the Tables will show that the great majority of the cases
of dysentery arose in ground-floor wards of the main building.

The ground-floor wards contain nearly all the patients with defective
habits, and of these wards li.l, C.l, H.l, E.l, on the female side, and
H.l, J.l, K.l, N.l, 0.1, K.l, on the male side, accommodate the most
degraded population; indeed, a very large proportion of the patients in
these wards are habitually wet and dirty. It will be seen that these
wards yielded an overwhelming majority of our cases. The up-stair
wards, the large “working” wards (S. and L.), and the villas, contain
veiy few patients with defective habits, and they contributed but few
cases of dysentery; moreover, cases occurring in these “clean” wards
were invariably solitary, and, for olndous reasons, the infection had but
little opportunity of spreading. On the other hand, wlien the disease
arose in wards containing degraded patients, it was the exception to find
that it was solitary, but as a rule small epidemics occurred or groups of
cases developed the disease within a few days of one anotlier. In the
tabulated summary of the cases, I have arranged columns showing the
mental state, the habiis, the employment in which the patient was en¬
gaged, and what their general health was considered to be at the on.sot
of the attack. Tlie results are very .striking- the majority of the patients
were suffering from advanc(‘d dementia of some form, and were defective
in their habits, but few employed themselves in any way and most of
them were in feeble or only moderate physical health.

Have not these facts an important bearing on tlie e])idt‘mics of dvsen-
tery which are noted as being so common during the eailv life of a new
asylum ?

Ur. Mott, in numerous reports and publications on dysentery in
asylums, points out the necessity of exercising great care in transferring
old cases of dysentery to a new asylum. Ur. Stansheld, in a discussion
of Ur. Mott’s paper before the Epidemiological Society, attributes the
early epidemics of dysentery at Bexley to patients transferred from other
asylums suffering from a latent form of the disease. Dr. Taylor, the
medical superintendent of the East Sussex Asylum, Hellingly, in his
annual report for the year ending March, 1905, refers to the early out¬
breaks of dysentery in that asylum, and states that, in his opinion, the
disease was imported from other asylums. He points out that dysentery
is a disease which is constantly liable to relapse, and draws attention to
the great difficulty in diagnosing the mild and atypical cases. Ur.
Candler, in his paper on dysentery in the Archives of Neurology, Yol.
III., gives numerous instances of the influence of transfers, both those
from ward to ward in the same asylum and those from one asylum to
another.

All of these authorities appear to be in agreement upon one important
point, namely, that some of the patients who have suffered from dysen¬
tery carry the infection for a long time afterwards. What proportion of
patients remain infectious for a prolonged period or what the limits of
this period may be there is no evidence to show, but there is little doiib*
that in some cases it extends to many months or even years. In tlie
light of these facts one can scarcely be surprised when Dr. Mott hiiii^
that, to prevent an epidemic of dysentery at a new asylum, the most
rational method would be to exclude all patients who had ever suffered
from the disease.

As a rule, the bulk of early admissions into a new asylum are old
patients who have been boarded out, or else large batches of chronic
lunatics taken in under contract to help to fill the asylum, and thereby
reduce the working expenses per head. In both of these cases an unduly
large proportion of patients will be found whose habits are defective and
wlio have other disagreeable attributes, for the wet and dirty lunatic is
always considered to be an eminently fit and proper person to be trans¬
ferred. This is just the class of case which is most prone to an attack of
dysentery, and, when attacked, is almost certain to disseminate contagion
lavishly amongst his neighbours. Again, a large proportion of the staff
of a new asylum have had little or no exj)erience in nursing, have not
been trained to properly observe tlveir patiemts, and are devoid of all
knowledge of hygiene and sanitary precautions. All these tilings enor¬
mously favour the spread of an infective disease, and greatly increase
the difficulty of coping with an epidemic of dysentery.

Indeed, the cliief weapon of defence against the spread of all iufec-

DVSENTKIIV AT L(E\(; CiHOVE ASYLUM

i\lb

live diseases is the adequate education of the statt'. With an increased
knowledge of their patients they become quicker at recognising when
anything is wrong, and the success of all preventive measures depends
to a large extent on their intelligent co-operation.

This, probably, accounts for the fact that epidemics of any magni¬
tude are less common in the older asylums than in those newly opened.

Reference was made in the third volume of these Archives to the fact
that, although dysentery was relatively as common in epilepsy as in
other forms of insanity, it was comparatively rare at the Epileptic
Colony, and this was attributed to the more healthy out-door life which
the colonists enjoy, to the fewer number of cases aggregated together,
to the vigorous methods of disinfection, and to the strict observation
kept on the patient when he returns to work. No doubt the importance
of isolation, disinfection, and notification of the patient on his transfer
from ward to ward cannot be over-estimated; but it is as well to point
out that almost all the colonists are clean, well-conducted patients, and
the great ma jority of them enjoy good physical health. It might there¬
fore be expected that they would be almost as immune to dysentery or
phthisis as sane people living in a similar community.

When a colonist becomes permanently demented and degraded in his
habits, he is obviously incapable of manual labour, and unsuitable for
colony life. He is then usually transferred to one of the sister asylums,
where he makes an unwelcome addition to a class of epileptics of very
different type to that at the colony.

Dr. Knobel, in a contribution to The Journal of Mental Science,’'
in April, 1906, attempts to explain the frequency of outbreaks of dyscui-
tery in new asylums by propounding the theoiy that one of the normal
habitats of the germ causing the disease may be the deeper layers of
the soil, and shows that many epidemics of asylum dysentery have fol¬
lowed shortly after disturbance of the subsoil. No doubt the grounds
of a new asylum are usually vigorously attacked shortly after the advent
of the patients. But Dr. Knobel fails to show cause why this vindictive
germ should almost invariably neglect those working patients who dis¬
turb its tranquility and attack those who toil not neither do they spin,
but whose habils are defective and whose health is, as a rule, impaired.

Later on in the same paper Dr. Knobel brings evidence to show ‘‘that
asylum dysentery can be caused by some micro-organism which normally
inhabits the colon and becomes pathogenic when the resisting power of
the tissue is sufficiently reduced.”

Our cases bring but little evidence either for or against the theory
that degenerative changes in the trophic nerve supply of the colon may
be an important factor in the disease: but it is obvious that this can

AllClliVES

31()

only be a contributory factor and not tlie principal one, for, if the ulcers
were truly trophic, no big asylum would ever be free from dysentery,
nor could we account for the disease occurring in epidemic form and
attacking the staff as well as the patients. Most of our patients were
debilitated, some of them very feeble, and many of them were known
to be the subjects of very obstinate constipation.

The disease occurred on the female side in a very virulent form; out
of 20 cases there were eight deaths, and several of these occurred within
three days of the onset of the attack. On the male side, out of 60 cases
there were only the same number of deaths which could be directly
ascribed to dysentery, but others have since died of different diseases.

Only two of our cases are recorded as having more than one attack
of dysentery, but several are noted as having simple diarrhoea, either
before or after the attack.

A column has been drawn in the table denoting whether the patient
attacked w^as a direct admission from the parish or a transfer from an¬
other asylum, and, as it is a rare disease outside asylums, it is probable
that but a very small percentage of the direct admissions had ever suf¬
fered previously from the disease. At the same time, it should be noted
that the first case of dysentery on the female side developed in a direct
admission from a workhouse infirmary after she had only been in the
asylum for three days—during this time she had been kept in bed and
had not mixed with other patients, and it is reasonable to suppose that
she became infected before admission.

Although the disease is said to be very rare in workhouses, in¬
firmaries, and other large institutions, there can be little doubt that it
does occur; only the type of people affected in these cases do not tend
to spread the disease and cause an epidemic: in other words, the condi¬
tions of these places approach more nearly to our w’orking villas and the
Epileptic Colony.

Only two cases have occurred amongst tlie staff, and both these were
in attendants who were actually engaged in nursing the dysentery
patients. Assuming the stools to be the chief source of infection, as in
typhoid, these are tw^o of the men one would have picked out as the
most likely to contract the disease.

In some of our cases a mode of infection was fairly easy to guess:
in other cases no source of infection could be traced, but there is always
the possibility of a mild atypical case showing few or no symptoms walk¬
ing about the wards and gardens and disseminating the disease.

Although there is no doubt that the stools of dysenteric patients are
infectious, it is, so far as I am aware, (|uite unknown how" long the
infective organism remains in the intestines after the stools have become

DYSKNTKlli AT LON(ji CiROVE ASYLUM

31T

normal. It may be, as Dr. Knobel suggests, that the micro-organism
nominally inhabits the colon ot many people, and only becomes a patho¬
genic under certain conditions.

Our ignorance as to how long a patient who has had dysentery re¬
mains a centre of infection, makes the question of transferring him back
to the ordinary wards very difficult. It is well to isolate all those with
defective habits for a long period, but it is obviously unfair to keep clean,
well-conducted patients, who are capable of fully appreciating their sur¬
roundings in a ward composed chiehy of dements with defective habits.
In the case ot (II) H. J., for example, a boy, whose mental condition
rather rapidly improved alter lie had recovered from an attack of dysen¬
tery, his chance of complete mental recovery would have been seriously
jeopardised by prolonged association wdth chronic unpleasant lunatics.
In those cases ^liere the habits of the patient are cleanly, there is pro¬
bably but little danger of the disease spreading. Again, some of the very
excited, noisy, and turbulent patients cannot be kept for long in an
infirmary ward where there are sick and dying patients whose friends are
allowed to visit them at any time, and occasionally it may be necessary
to transfer them back to the ordinary wards before one w’ould care to do,
if they could have been suitably accommodated in the isolation wards.
In these cases, liowever, they can always be kept strictly apart from
other patients for a further period, as urgent mental symptoms of this
kind generally demand treatment in bed in a single room.

In all casL's wlicn a patient is transferred to another ward, his pa[)ers
are distinctly marked, and tlie attendants liave orders to keep careful
observation on the behaviour of the bowels, and draw the attention of
the doctor to anything abnormal; moreover, the patients are always
accompanied by their temperature charts and clinical records, which
contain an account of the disease.

The first case of dysentery at Long Grove occurred in II.1 ward on
August 6th, 1907. -Sine days previously a patient in the same ward,
who was addicted to rubbish eating, was reported as having an attack
of diarrhoea, but there was nothing in the motions or the general condi¬
tion of the patient suggestive of dysenteiy, and, after one day in bed,
he was again in his usual health. The first case (1), C. D., was a healthy
man, aged 57, who was admitted into the asylum on July 12th; he had
been continuously under treatment since 1903, and had been in two
previous asylums; the medical superintendents of both these institu¬
tions were written to, but both reported tliat he had not had dysentery
whilst under their care.

The attack commenced with headaclie and a feeling ot general ill¬
ness, tongue furred, breath offensive, temperature (axillary) 99*8, no

AEClllVES

ai8

physical signs. He was transferred to J.l ward for treatment, and the
dysentery was not recognised until some 12 hours later, wlien he passed
his first abnormal motion containing a trace of blood and a considerable
quantity of mucus. He was isolated in a single room and treated with
t he usual precautions. The attack lasted a fortnight, but he was kept
in J.l ward for two months.

Un September Gth eleven cases of diarrhoea were reported on the male
side—all these cases were on mince diets, and the majority were old,
feeble people—eight out of the eleven were in J.l intirmary, nine out of
the eleven were in their usual health next day, and the other two were
considered as cured on the moriiing of the 9th and 10th respectively.
The second case of dysentery (2), E. J.G., occurred in a patient suffer¬
ing from general pamlysis, who was admitted on August 13th direct
from the parish and who had never before been under certificate. He
was very demented, his habits were defective, he was generally en¬
feebled and had paresis of the right side. He w'as transferred to J.l ward
on August 28th for infirmary care. He w as one of the eleven cases above
mentioned that had an attack of “ simple'' diarrhcea lasting from Sep¬
tember 6th to 8ih; during this attack there was nothing in the motions
or constitutional syniptoms suggestive of dysentery, and on the morning
of September 9th he was considered to be in his usual somewhat feeble
health. On the same evening his temperature rose to 103® and he passed
a motion containing almost pure blood w ith some mucus. His attack of
dysentery lasted about a w^eek. It is possible either tliat his preliminary
diarrhoea was really dysentery, or that it had lowered the power of re¬
sistance of the bowel to bacterial infection. Eitlier of these suppositions,
if true, may account for the fact which has been noted by some observers
that epidemics of dysentery often coincide wdth an increase in the num¬
ber of cases of simple diarrhoea. It will be seen that (1), C. D., the only
known source (d the disease up to this time was still in J.l ward. The
next three cases occurred in R.l ward, two being “ transfer ” patients and
one a “ direct ’’ admission. The history of one of the transfer patients (5),
T. W., recorded an attack of simple diarrhoea in July, the same year, but
in neither of the others was there any history of bow^el trouble.

It will be seen from the table that after dysentery had once started,
the male side was never free from the disease for more than a few weeks,
but in May, June, and July, 1908, only three cases occurred in the
w hole asylum.

Several other cases are w orthy of special mention : Case (7), tl. C., a
quiet, clean, w^ell-conducted imbecile, was transferred from 0.2 ward
to J.l w'ard on November 2nd, as he needed rest in bed for svnovitis of
the knee due to injury. He w^as nursed in the same dormitory as the

DVSKNTKRY AT LOXCr GROVE ASVLL M

ah)

dyseiiteiy patients, and on iSoveinber oth lie developed tlie disease. There
is a strong probability that he became infected in J.l ward, as there
has been no case before or since in 0.2 ward, and from the history of the
patient it appears that he had been free from any attack of a diarrhcecul
or dysenteric nature during his years’ residence at the previous asylum.
This suggests that the ihcubation period may be four days or less.

Case (llj is rather puzzling: H. J., a boy of 18, sulfering from acute
mania, first attack, was admitted direct from the infirmary on December
17 th to iSM ward. On December 24th he developed dysenterj'. Up
to that time he had mixed very little with other patients in the ward, as
he was in bed in the padded room on account of mental excitement. Uis
liabits were wet and dirty. Tliere had been no previous cases from this
ward, nor had any been returned there. The attack commenced suddenly
with malaise and abdominal pains; there were numerous motions con¬
taining blood and mucus, but there was no pyrexia, and tlie mental symp¬
toms abated. He was given a large dose of castor oil, and was apparently
well in two days, the motions after tliis being normal and the mental
symptoms returning. There is no doubt that he had a sliort or abortive
attack of asylum dysentery.

Case (16), F. W. G., a patient sufiering from general paralysis, was
transferred to J.l on January 1st, 1908; convulsive seizures and transient
paralysis occurred. The patient became progressively weaker, and
died on March 18th. He was wet and dirty - passed everything in the
bed—the motions were certainly carefully observed and were reported
as being normal; no blood or mucus was ever seen. At the autopsy very
extensive ulceration of the colon was discovered. One other case, (45),
W. W., passed normal motions, which were seen by the doctor, for two
days preceding death, and jfod mortem there was very extensive ulceration
of the whole of the large intestine. One male patient had two attacks,
AV. AV., (13) and (19). The first attack lasted eight weeks, and a similar
interval separated the two attacks. One female, Case M. S., had three
attacks in nine months, (4), (11), (19), in the third of which she died,
and another female. Case J. A. F., (13), was discovered to have ulceration
of the colon, which appealed to be of very long standing, though she
died within a few hours of the commencement of her acute attack. If
some of these case of second attacks are really cases of chronic or
relapsing dysentery, in which, in spite of the absence of all symptoms,
the ulceration has never entirely healed and which still remains infective
and subject of acute exacerbaiions of the disease, they are a very real
danger to the community with whom they are housed, more especiallv
when their habits are defective; and at present there appears to be no
way of diagnosing these cases until they have had more than one attack

320

AilClllVES

or exaccjbutioii. Aiioth.^’ possii)le way oi tlie disease spreading is that
some patients wlio liave sulVered from it may aei as “ dysentery carriers/'
that is to say, althougli tliey completely recover, the germ remains in
some part ot tiieir intestinal tracts for months or years. Some epidemics
ot typhoid Jiave been proved to originate in this manner irom tlie so-
called “ typhoid carrier," who tliough apparently quite healthy tliem-
selves pass typlioid bacilli in the stools.

The two lemale cases just referred to are woi tli recording in a little
more detail. The first, M. S., (4), (11), (19), was a transfer who had
been under certificate since 1898, and had been in two previous asylums.
She had an attack at Claybury lasting from November 19th to December
1st, 1899; she relapsed on December 15th and recovered on January 14th.
1900. She had a second attack in 1902; she was transferred to another
asylum in 1903, and during her four years there is said to have been fre.
from dysentery and diarrhcea. Her first attack at Long Grove commenced
on January 15th, 1908, and she was regarded as cured on 8tli of Feb¬
ruary. Her next attack lasted from J uly otii to 18th. On September
22nd she was noticed to be looking ill, and the temperature was found to
be 105°; tlie next day she was quite collapsed with signs of symptoms of
peritonitis; she died the same evening. She had vomited once, but there
had been no action of the bowel since the commencement of her acute
illness. Fast mortem there were old peritoneal adhesions around the
lower part of the colon in the left lower quadrant of the abdomen; there
was recent peritonitis and some semi-purulent fluid in the lower part of
the abdomen and pelvis; no actual perforation was found, but there
were many peritoneal adhesions which made the examination for this
very uncertain. The whole of the mucous membrane of the middle
portion of the sigmoid ,colon was gangrenous. There were no signs of
old ulceration and no thickening of the coats of the bowel. This is the
only one of our autopsies in which there were peritoneal complications.

The second case, J. A. F., (13), was admitted to the Female Hospital
Villa on July 2nd, 1908, suffering from melancholia of the agitated form.
She did not improve in any way, her mental symptoms became more
marked, she was intensely restless and apprehensive, very defective in
her habits, at times refused food, and had to be fed by nasal tube.
On August 28th, at 2.15 a.m., she had a rigor after which she collapsed.
The bowels were relaxed twice. Slie was treated with stimulants, etc.,
but never rallied, and she died at 4.20 a.m. The motions did not contain
blood or mucus, and the dysentery was not recognised during life. At
the autopsy she was found to have pneumonia and very extensive ulcera¬
tion of the colon. The ulcers were round and oval with thickened bases
and edges and around them was much pigmentation; they had the

DYSENTERY AT LONG GROVE ASYLUM

321

appearance of being of long standing. There was also much general
congestion of the colon and very extensive superficial loss of mucous
membrane, so she probably had an acute attack of dysentery supervening
upon an old chronic dysenteric ulceration. This patient was a direct
admission to the asylum, and had never been previously certified.
She had once before been under treatment at an infirmary for mental
disorder. There had only been one case of dysentery previously at the
Hospital Villa, and this had occurred four months before, and no cases
that had suffered from dysentery had been transferred back to this villa.

The first of the following tables has already been referred to. The
second gives a short abstract of the post-mortem notes on the condition
of the bowel in those cases which died either directly from dysentery or
from some other disease after recovering from dysentery.

The third table is a record of the ward-to-ward transfers of all the
cases both before and after the attack. It will be noticed that many of
the cases have been in numerous different wards; this is unavoidable in
the opening of a new asylum, and the moves are likely to be much fewer
now that the institution is full. In the last table an asterisk indicates
the ward at the time of onset of the dysentery.

322

AKCmVKS

Ta blk 1. —MALES.— continued.

DYSENTERY AT LONG GROVE ASYLUM

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DYSENTERY AT LONG GROVE ASYLUM

325

Table III.—MALES.

Short Abstract of P. M. Eeport on Condition op Intestines.

9. J. D., 452.—Intestines appeared normal, no ulceration, no scars. Cause of
death, general paralysis.

10. W. H. A., 461.—No signs of old or recent ulceration. Cause of death,
general paralysis.

14. G. E. C., 338.—Superficial ulceration of the whole of the large intestines, only
small islands of normal mucous membrane left.

16. F. W. G., 413.—Extensive recent ulceration throughout the whole of the
large intestine; the ulcers were still discrete and varied from the size of a pea to
that of a shilling.

18. A. J., 773.—Tuberculous ulcers of both large and small intestine.

27. J. R. S., 765.—Typical dysenteric ulceration of rectum and sigmoid ; the
edges of the ulcers were not thickened and the ulceration appeared to be quite
recent.

35. E. F. B*, 630.—Very extensive recent ulceration of whole of large intestine,
most marked in sigmoid and rectum. No signs of old ulceration,

45. W. W., 1105.—Very extensive ulceration of the whole of the large intestine.

56. W. M., 1238.—Mucous membrane of large intestine much congested through¬
out, with some superficial loss of surface. Four typical dysenteric ulcers in c»cum.

60. J. C. H., 1223.—Lower part of colon greatly conges'ted, numerous superficial
erosions of mucous membrane.

In three of these cases—9, 10, and 18—dysentery could not be said to directly
contribute to death. In one case, No. 52, no autopsy was done on account of
objection by friends.

This gives a case mortality of 13'3 per cent, for the males.

Table IV.—FEMALES.

Short Abstract of P. M. Report on Condition of Intestines.

5. E. D., 280.—Numerous slaty grey patches on mucous membrane of colon, no
congestion, no ulceration.

6. M. A B., 689.—Mucous membrane much congested with patches of a slaty grey
colour. One ulcer in cwcum, and ai'eas of superficial necrosis.

7. C. H., 732.—^Acute necrosis of iraicoiis membrane of large intestine, with
superficial ulceration.

10. E. M. A., 383.—In upper part of large intestine were small areas of ulcera¬
tion and intense congestion. In the lower part the whole of the mucous membrane
was sloughing.

13. J. A. F., 1072. - Marked congesiicn throughout the large intestine. Numerous
ulcers, round and oval, in colon ; edges thickened and pigmented, and some show
thickening at base, they have evei’y appearance of being old ; there is also very
extensive superficial loss of mucous membrane which appears to be recent.

15. M. B., 268.—Intense congestion of mucosa of large intestine with extensive
superficial ulceration, giving it a worm-eaten appearance.

16. J. H., 632.—Whole mucosa intensely congested with irregular superficial
ulcers scattered throughout.

17. J. M., 1086.—Intense congestion of both small and large intestine, small
ulcers in the last six inches of the ileum and very extensive ulceration throughout
the whole of the colon.

19. M. S., 131.—Old peritoneal adhesions and recent peritonitis; the whole of
the mucous membrane of the middle portion sigmoid was sloughing.

In the first of these cases there were no symptoms of dysentery for a fortnight
before death, and the patient died from other causes. This leaves eight deaths out
of 20 cases, giving a case mortality of 40 per cent., or three times as great as the
case mortality on the male side.

Table V.—TEANSFERS OF MALE PATIENTS FROM WARD TO WARD.

326

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DYSENTEEY AT LONG GEOVE ASYLUM

327

328

AKCUIVES

Conclusions.

Trom studying the literature and from clinical experience, I have
come to tlie following conclusions: —

(1) That “Asylum Dysentery is an infectious disease caused by the
action of an organism or group of organisms.

(2) That the disease is communicable mainly if not solely by contact
with the excreta of infected persons.

(3) That the disease is by no means confined to asylums or to the
insane, but that the frequency of its occurrence in epidemic form in
asylums is largely accounted for by the defective habits of many of the
inmates.

(4) That the disease occurs in patients suffering from all forms of
mental disorders but chiefly those in feeble physical health, and that the
great majority of patients attacked are of defective habits.

(5) That there is no evidence supporting the suggestion that a nervous
or trophic condition has any direct influence in the causation of the
disease, but that the persons attacked are frequently those subject to
severe and chronic constipation, w^hich may be regarded as a predisposing
cause.

(6) That different epidemics of the disease vary greatly in virulence.

(7) That the disease occurs in many mild atypical and abortive forms
which are difficult to recognise, and that in spite of all reasonable care
it is frequently diagnosed as simple diarrhoea or escapes recognition
altogether.

(8) It is highly probable that some persons who have had the disease
become ‘‘ dysenteiy carriers,'* and that the organism causing the disease
continues to live in the intestine, possibly causing recurrent attacks of
dysentery or possibly causing no symptoms in the carrier " but capable
of transmitting the disease to others.

(9) The isolation of all suspicious cases and disinfection of all clothing
with which the patient has been in contact are essential.

REFERENCES.

Mott and Durham. Rejwrt on Dysentery in the London County Asyliini.«?.
Mott. “ Archives of Nenrolo<Ty.” Vol. p. 7;!.^^.

Mott. “Trans. Epiderniolop^ieal Soc. ” Vol. xxi., 1901-02.

Knobel. Journal of Mental Srienrc. April, 1900.

Candler. “Archives of Nenroloc;}'.” Vol. iii., p. 29^1.

Taylor. East Sussex, Hellingly Asylum Reiwrt, 1905.

STATISTICS BELATlIsG TO THE PERCE.XTAOE INCIDEiXCE

OF INTRACEREBRAL AxXD SUBDURAL HEMORRHAGE

AND DEPOSIT IN THE INSANE.

U\ V. \V. MOTT, M.D., F.K.S.. F.K.O V.

I have coIleL*te<l llie statistic.^ lelating to I,U2G necropsies coucIucUhI
at Claybury Asylum by my assistaut-s or myself during the past ten years,
with a view of ascejtaining the percentage incidence of intracerebral
and subdural haemorrhage and deposit in the insane. The results are
recorded in the subjoined table, trom which the following conclusion>
may be deduced. The total j^ercentage of intracerebral htemorrhage is
1*2 per cent. With the exception of two cases of doubtful general
paralysis, the haemorrhage occurred in the subjects of insanity other
than general paralysis. In the case of subdural haemorrhage and deposit,
especially in males, there appeared to be two separate morbid conditions:
(a) Cases of undoubted subdural hsemorrhage in elderly people associated
with arterial degeneration and cardiac hypertrophy; (b) Cases of mem¬
brane formation of a similar nature to that found in general paralysis.
Among the females the former class of case was not in evidence. Com¬
bining therefore the intracerebral and subdural types of hsemorrhage
w’e have a sum total of 85 cases out of 1,926 necropsies, which is about
2 per cent. In practically every case of intracerebral and subdural
Inemorrhage there was associated chronic vascular and renal disease
{vide Table); a condition markedly different from that found in cases of
chronic pachymeningitis, in which the heart, together with the other
viscera, usually sliowed some wusting; especially was this the case in
the subjects of general paralysis of the insane.

- i

M.dc.

Fmnalc.

1

Average weight of the iiismie heart in grains* .

Average weight of the heart in tlie eases of intraeerehral |

800

1 -i?'

hyeraorrhage (M. Ih; F. 9) ... ... ... ...,

ttH)

:!U0

Weight of heaviest heart ... ... ... ... j

t)(X)

44(1

Weight of lightest heart ... . ... .. '

810

' 20(1

Number of hearts above average weight ... ... . . ... ^

16

.)

Number of hearts below' average w'eight ... .. '

4

* Obtained fnnu an avei’ag^e uf 100 male and 100 female consecutive autopsies.

330

ABCHIVES

Male. reiiiale.

Average weight of heart in causes of siihdiiral hannorrhage other

than general ])aralysiK of the insane (M. 12 ; K. 1) .. 402 2<J5t

Numl>er of hearts above the average weight . 10

Weight of heaviest heaH ... . . ... o40

Weight of lightest lieart ... ... ... ... 200

Average weight of heart in eases of haiuiorrhagie j)aehynieiiiri- ^

gitis other than geneial j)aralysis (M. 7; F. 13) ... .. 27o 238

Average w’eight of heart in cases of haemorrhagic pachymenin¬
gitis of general paralysis (M. 18; P.2) ... 200 , 2o7

Total number of deaths (out of 1,020) occurring at 4o years and

under ... ... . ... ... 3.V» 343

Number of eases of intracerebral haemorrhage occurring at 47)

years or under ... ... .. .. ... ... ... 3 I

Numl)er of cases of subdural haiinorrhage and ])achymeningitis

other than genen^l paralysis occurring at 4o years or under 1 1

Number of cases of hmmorrhagic ])achymeningitis in general ;

})aralysis occurring at 45 years or under ... ... ... 11 1

t One case only.

'I'.viiLK showing the incidence of Cerebral HaBmorrhage and Ohionic
Pachymeningitis in the Insane.

Pcinak’N.

IV-tiil.

1

Total number of necro|)sies performed

‘337

989

1 "

1028

Number of ca.ses of general jjaralysis

„ insanity other than general para-

334

127

, k)i

lysiK .

intracerebral hiemorrhage in 1

803

882

1 1W.‘.

1

cases of general j)aralysis ... !
,, hamiorrhagic ])achymeningiti.s '

0(21")

o

0

in cases of general }>aralysis... i

,, intrac*erebral hmmorrhage in *

cases other than general para-

18

o

“

20

iysi«. .1

Percentage incidence of intracerebral hmiiiorrhage

i if

25

on total number of necropsies ... .. ...

Number of cases of subdural ha3morrhage in cases |

1-7 %

10

1-2 ,.

otlier than general paralysis... '
,, Inemorrhagic pa<*hymeningitis

in cases other than general

12

1

13

paralysis

(Combined total of cases of cerebral hajmorrhage—

t

13

20

intracerebral and suVjdural

28 = 3

K.) =- 1

:38=2.

i

jAft Tsoscorr h Son, Lio. LoNoolt

-Ul'li j.- }.