-A8¥ET7M For INGANDi-GetUMBUSr-OHIO. 
A-. Ik 
Pathological Bulletin, No. I. 
REPORT UPON THE 
pathology of a Cage of tjeqei'al faraljgig 
BY 
C. L. HERRICK, 
Professor of Biology in Denison University. 
■iSnrcrMjDBTEMBER, 1893. REPORT UPON THE PATHOLOGY OF A CASE OF 
GENERAL PARALYSIS. 
By C. L. Herrick, Professor of Biology at Denison University. 
Note of Transmissal.* 
Dr. A. B. Richardson, Superintendent of the State Hospital for the 
Insane, Columbus, Ohio, 
Dear Sir: In pursuance of your suggestion, a microscopi- 
cal examination has been made of the specimens placed in my 
hands with results which are detailed beyond. While the his- 
tory of the case, as you informed me, warranted us in expect- 
ing only the usual lesions of general paralysis incident upon al- 
coholism it was thought worth while to not simply make such 
examination as should detect the expected lesions but to make 
the study extended enough to afford a somewhat complete pic- 
ture of the diseased brain as a whole. Circumstances have pre- 
vented the completion of the task in the way at first contem- 
plated. The employment of the slow and tedious fibre-stain 
methods was rendered impossible by pressure of work immedi- 
ately upon reception of the specimen. The present paper is 
devoted almost exclusively to the cells of the various portions 
of the brain. It is thought that what we now need is the col- 
lection of minute, detailed data presenting the facies of a path- 
ological state in its entirety and we have accordingly presented 
illustrations of the various regions even where involving some 
repetition and, in order to make the account more generally 
useful, some historical and physiological suggestions are added. 
Unexpectedly the distribution of the degenerated structures has 
thrown incidental light upon an important morphological prob- 
lem, reenforcing generalizations derived from the comparative 
realm. 
Hoping that the paper, imperfect as it is, may serve its 
purpose in preparing the way for more systematic and useful 
work in the same direction. 
I am yours respectfully, 
C. L. Herrick. 
Published in the Journal of Comparative Neu- 
rology, September, 1893. Vol. Ill, p. 141. 4 
Pathological Bulletin. 
HISTORY. 
Supplied by the Medical Corps of the Columbus Hospital for 
the Insane. 
J W. S was admitted to this institution June 
20th, 1891. He was a native of Ohio, forty years of age, a 
merchant and a man of good education. He had been ad- 
dicted to the use of intoxicants for several years but was more 
temperate within the two or three previous to his admission. 
There was no history of specific disease and he had been a man 
of good character in his community and of active business 
habits. The mental symptoms began about six months previous 
to admission. When admitted he had delusions of grandeur 
and was becoming somewhat demented. He imagined he was 
quite wealthy and was anxious to run for the office of Governor 
or of President of the United States. His pupils were unequal, 
there was incoordination in gait and he had the characteristic 
defect in speech that marks the paretic. There was no history 
of insanity or nervous disease in his family and the cause as- 
signed was financial trouble, of which he had had considerable. 
His intemperance was also in my opinion a cause. He contin- 
ued an inmate of the institution until his death, which occurred 
Jan. 8th, 1893. 
He became rapidly more demented and the paresis in- 
creased. His digestion was good during nearly all of the time 
and only failed him within the last month or two before his 
death. There was no evidence of focal lesion in a local paralysis 
and the disease pursued the characteristic history of general 
paralysis. I regret that the history is so meager, but while we 
could add illustrations of his delusions they would be of no 
value in a Pathological Bulletin. The previous history is diffi- 
cult to secure, but there was nothing very characteristic in his 
life as far as we can discover. He was a man of active business 
habits and at one time was worth considerable property, but he 
lost it all, his reverses* in part at least, being due to his 
dissipation. 
It is further stated that the first symptoms of motor en- Herrick, Pathology of General Paralysis. 
5 
feeblement were a slight speech disturbance, in the nature of a 
blurring of the articulation, and awkwarkness in the gait that de- 
noted slight incoordination. These facts are significant inas- 
much as it will be shown that the most seriously affected corti- 
cal areas are those in Broca's region and in adjacent parts, while 
still more serious lesions are located in the coordinating centers 
of the thalamus nnd mesencephalon. No sensory aura nor 
other disturbances, nor any visual, auditory, or olfactory hallu- 
cinations were detected. As it was not expected that a careful 
pathological investigation would be possible, no dynometric or 
aesthometric tests were made nor were systematic registrations 
of temperature or urine analyses attempted. * 
NATURE OF THE DISEASE. 
Mendel says of the etiology of progressive paralysis: 
"From the results there can remain no doubt that the es- 
sential thing is interstitial inflamation. The cell-multiplica- 
tion, development of spider cells, the increased excretion of 
intercellular substance, these leave no doubt in this connection, 
and at the acme of the disease, according to my observation, 
the evidences of this inflamation are never absent." 
"In acute paralysis the nucleary proliferation and the de- 
*The following extract from a letter from Dr. Richardson re- 
ceived too late to be inserted in the proper place will be of interest: 
"I have just learned a few facts in the history of J. S., whose case 
you are investigating, which may be of interest in case it is not too late 
to include them in the record. He was a man of more than usual 
business activity and conducted a mercantile business in a small 
town. He was always good hearted and indulgent and inclined for 
years to the use of intoxicants in moderate amount when with his 
friends. Through his indulgence to his friends his business became 
complicated during the years 1888 and 1889, and he was compelled 
to make an assignment about the close of the latter year. In the 
spring of 1890 he had an attack of La Grippe and after that never 
seemed as well as before, and was somewhat despondent. He grew 
worse that Fall and his disease began to change to a state of exalta- 
tion. He became talkative and excitable and enthusiastic over busi- 
ness, until finally, during the winter of 1890 and 1891, his actions 6 
Pathological Bulletin. 
velopment of spider cells is not great while they are replaced by 
the phenomena of hyperaemia of the vessels or stasis through 
the collection of blood corpuscles in the adventiva. In the very 
aged the preceding processes of irritation are only here and 
there to be noticed, or not at all; the general atrophy extends 
to include spider cells and granules." "The change in the 
cell bodies is, so far as our methods show, a secondary process, 
which in many cases can only be made out by microscopic ob- 
servation, in a very limited extent, while in other cases, as 
above shown, producing a very remarkable alteration." 
"Changes in the membranes are likewise, in the rule, sec- 
ondary. . . . The pia as well as the dura, in most 
cases, is implicated through the disturbances in the circulation 
in the brain itself which react upon it, as well as through the 
progressive diseased condition of the vessels, From all these 
considerations I conclude that progressive paralysis is a diffuse 
interstitial cortical encephalitis resulting in brain atrophy. 
"The beginning of the process is a transmigration of leuco- 
cytes and it is accompanied by an increase of the connective 
elements. The compression of the capillaries and of the small 
arteries through the accumulations in the adventitious sheath 
disturbs the regularity of the nutrition of the nervous elements, 
became so unreasonable that he was adjudged insane and sent to the 
asylum. He remained there until about May of 1891, during which 
time he became more quiet and was finally taken home on a visit. 
In June of'91 while at home he had a sudden epileptiform seizure 
with hemiplegia on the right side, which, though not complete, lasted 
for about three weeks. His speech was much worse after this than 
before, and in August of the same year he had an attack of speech- 
lessness lasting for a day or two, during which time he was entirely 
unable to talk. Soon after this he was returned to the asylum where 
he remained until his death and did not afterwards have any sudden 
attack nor any symptons of local paralysis. The history during this 
time we have heretofore narrated. There is no history of insanity in 
the family. During the four years previous to his death he did not 
drink any. In 1888 his only child became lost and the excitement 
and worry in the search for him was a severe shock to him and his 
friends were afraid at that time it would cause some mental trouble." Herrick, Pathology of General Paralysis. 
7 
producing degeneration of the latter and finally leads to atrophy 
and shriveling." 
Mendel suggests that the great diversity in the symptom- 
ology of general paralysis may be due to the existence of varie- 
ties with an interstitial and a parenchymatic origin. 
The present case shows sufficiently well that the intensity 
of the degenerative process varies greatly in various regions. 
This is sufficient to account for great diversity in the facies of 
the disease. It would seem that there could be no limit to the 
range of variation where the slightest change in the seat of dis- 
turbance might interrupt a different set of channels of commun- 
ication. Historically the opinions of the cause of the malady 
have varied between wide extremes. Meschede, in 1865, con- 
sidered the alteration in the ganglion cells of primary impor- 
tance and considered the disease a parenchymatous inflamation. 
Mangan, in 1866, described it as an interstitial encephalitis, 
while Rokitansky and, finally, Luys referred the trouble to the 
neuroglia; the latter called it diffuse interstitial sclerosis of the 
neuroglia. 
It is not unnatural that vaso-motor changes should be ap- 
pealed to as fundamentally important, as has been done by 
Obersteiner, Thompson and others, in fact it is difficult to see 
how the undoubted connection between mental strain, on the 
one hand, and vaso-motor disturbance of alcoholism on the other, 
with the degenerations of general paralysis is to be explained 
without admitting, via functional hyperaemia and temporary 
vaso-moter incordination, the graver and more permanent changes 
which should make way for morbid nutritive changes in the 
cells. If metabolism is altered by altered blood pressure it 
would be natural that other cellular elements besides the cortical 
cells should be modified. It would seem more rational to sup- 
pose that all the cellular structures in the region affected should 
feel the effects of vascular disturbance and react, each after its 
kind, while reciprocally modifying each other and thus the 
course of the disease. Instead then of drawing a distinction 
between interstitial and parenchymatous phases we may 
restrict ourselves to such practical classification in accordance 8 
Pathological Bulletin. 
with predisposing cause and the sequence of symptoms as shall 
most nearly correspond with the requirements of treatment. 
The prevailing unwillingness to recognize the great influence of 
alcoholism may account for the failure adequately to construe 
the influence of slight vascular disturbances if sufficiently long 
continued. 
It will be gathered from our own observations that the 
facts seem hardly to bear out the statements of Hirt: "This 
view, according to which the atrophy is the primary process, is 
in all probability correct, though it is still combatted by many 
authorities (Mendel), who look upon the death of the nerve 
fibres as the secondary, upon the increase of the connective tis- 
sue, the thickening of the vessel walls and the appearance of 
spider cells as the primary process ('encephalitis interstitialis')." 
In the present case, however, the development of the spider 
cells, upon which Bevan Lewis, Mendel and others lay so much 
weight, is a very insignificant factor. The most important one 
seeming to be the involvement of the blood-vascular system and 
the greatest cellular modifications are seen in the motor co-ordi- 
nating centres of the axial lobe. Our case supports the view 
of Zeigler1 that the phemomena of general paralysis are not 
uniformly inflamatory "but not rarely simply degenerative 
processes in the meninges and the cortex." He says: "Es ers- 
cheint danach die gestorte Ernahrung und die Degeneration der 
Ganglienzellen und Nervenfasern als die wesentliche, und die 
entzundliche Infiltration und die Zunahme der fibrillaren Stiitz- 
substanz sind zwar fiir die anatomische Beurtheilung des Pro- 
cesses, nicht aber fiir die Krankheitssymptome von wesentlicher 
Bedeutung. " 
Mierzejewski and Voisin regard these spider cells and 
fibrous aggregates, which are not noticeable in some cases, as 
coagula of fibrin derived from homogeneous masses which may 
contain nuclei. It may be that diverse structures have been 
combined under this name. The "spider cells" which were 
1Lehrbuch der Allgemeinen Pathologische Anatomie und Pathogenese, 
4th Edit. 1885, p. 591. Herrick, Pathology of General Paialysis. 
9 
sparingly present in this case may be of the character of a dif- 
fuse stroma. Ziegler says that the spider cells are frequently 
not increased in number but simply more conspicuous because 
of the atrophy of other parts of the cortex. The fact referred 
to by Lewis that representativeness is a function early lost in 
the course of general paralysis may have its anatomical explana- 
tion in the fact that slight sporadic changes would interfere with 
associational tracts (association being intimately connected with 
representation) before becoming sufficiently pronounced to in- 
terfere with the direct presentational processes of perception, 
etc. In fact, according to Tuczek, there is a marked primary 
atrophy of the fine medullated nerve fibres, particularly in the 
outer layers of the cortex, in the tangential "associational" 
fibres which run parallel to the surface. Friedmann describes 
four varieties of atrophy of the white matter and others have dis- 
covered secondary degeneration in the dorsal columns of the 
the cord. Our methods were selected with reference to the 
cells and, whether for this reason or because no genuine degen- 
eration of the fibres had set in, only sparing and unimportant 
degenerations of white matter were encountered. 
In determining the cause and nature of the circulatory 
changes preceding cerebral degeneration a thorough knowledge 
of the nature and reactions of the blood and lymph which fill 
the delicate cerebral organ as fluid fills a sponge is necessary. 
The brain is almost as really an erectile tissue as the pan- 
creas and we already know enough to be convinced that slight 
changes in pressure may become the occasion for the rapid pro- 
liferation of the corpuscles and that the presence of small quan- 
tities of certain substances may greatly change the balance of 
the fluids in the capillaries, lymphatics and tissues. R. Heid- 
enhain has conducted very elaborate investigations upon the 
lymph1 and finds that there are lymphagogues or substances 
which increase the formation of the lymph. Various extracts 
of invertebrate muscles, egg albumen, peptone, etc., are 
1Versuche und Fragen zur Lehreivon der Lymphbilding. Pflingers Archiv 
f. d. ges. Physiologic XLIX, p. 209. 10 
Pathological Bulletin. 
among the lymphagogues.1 It is shown by experiment that in 
this case, as when sugar is injected into the veins, the capillaries 
exert a genuine secretory influence. In the latter case the 
blood is extracted from the tissues by the dehydrating action 
of the sugar. It seems probable that alcohol would operate 
in a similar way. There are many things which suggest that a 
sort of protoplasm poisoning is an early incident to the devel- 
opment of the circulatory changes preceding paralysis. 
One must remember that even in the normal state the va- 
riations in metabolism find other expressions than in the form 
and reaction of the cells. Carazzoni2 has shown that the ratio 
of solids in the cerebro-spinal fluids is greater in the morning 
than in the evening in the percentage of 1-35 to 100 and is more 
alkaline in the morning also. Substances injected into the ab- 
dominal cavity make their way into this fluid after half an hour 
or more which is, however, more slowly than their entrance into 
the blood or even the aqueous humor, as would be expected. 
The theory that prevails to some extent in this country 
that the moderate use of alchohol serves to substitute to some 
extent for proteids in the diet has apparantly been exploded by 
Minra's researches.3 A slight increase of albumen is regarded as 
evidence that alcohol acts like chloroform as a protoplasm pois- 
oning which may be expected as one of the incidents of early 
stages of the pathological condition now under consideration. 
(Cf. Heymans. Sur Faction toxique et antiseptique du chloro- 
form etc., Ann. Soc. med. Gand. 1892. ) 
EXTERNAL CHANGES. 
Macroscopically there was less alteration than might have 
been legitimately expected. Plate A. illustrates the appearance 
of the brain after the removal of the membranes. The mem- 
branes were slightly adherent but not closely enough to pro- 
duce decortication upon their removal. The characteristic 
1 Centralblatt f. Phys. 8/6. 
y Centralblatt f. Phys. VI. 14. 
'Ueber die Bedeutung des Alkohols als Eweisssparer in der Ernahrung des 
gesunden Menschen. Zeitsch. f. Klin. Med. XX, 112. Herrick, Pathology of General Paralysis. 
11 
opalescence was noticed on the surface of the fresh brain and 
some hemorrhagic patches along the sulci. The cerebellum 
was superficially injected but section shows nothing abnormal in 
its deeper portions. The membranes themselves were thickened 
but there was no evidence of acute inflamation. The cortex 
itself appeared nearly normal but the sulci were more conspic- 
uous than would be expected from the age of the subject. The 
atrophy was especially marked about the insula, fissure of Ro- 
lando and the tip of the temporal lobe and not noticeable in the 
occipital. A wax model made by the method of impregnation 
of the right hemisphere with Japan wax brought out the atro- 
phy more clearly as the shrinkage incident to the method was 
more marked in the regions mentioned. The surface of the 
brain was minutely pitted throughout its extent. The figure 
sufficiently represents the configuration of the right hemisphere. 
The weight of the entire brain was about 58 oz., and there 
seemed to be an abnormal amount of ventricular fluid. 
THE MEMBRANES 
Circumstances have thus far prevented giving special atten- 
tion to the meninges but, while somewhat thickened and ad- 
herent and while the surface of the brain when removed had the 
peculiar opalescent character so often described, the most notice- 
able changes are connected with the vessels. In the sinuses 
lying in the sulci great accumulation of leucocytes has taken 
place and the leucocytes fill the considerable space about the 
vessels and may be readily seen entering the brain and collecting 
at various levels below the surface. These changes are simply 
analogous to those which are taking place in the vessels within 
the cortex and, like the latter, point to an inflammatory condi- 
tion. 
In those regions in which the morbid changes are most 
marked the blood vessels are also greatly affected. The first 
characteristic of change is the increased number of white corpus- 
cles and their transmigration into the surrounding tissue. There 
can be no doubt that normally this transmigration is continually 
taking place. The large pyramidal ganglion cells almost invari- 12 
Pathological Bulletin. 
ably have a certain number about their bases or active pole. 
They present a great variety of stages between the full, plump 
nuclei which have recently reached the cell and the dark, shriv- 
eled, exhausted cells which seem to have yielded their nourish- 
ment to the nerve cell. Whether as cause or effect, the condi- 
tion of general paralysis is accompanied by an abnormal 
collection of leucocytes. These gather in great numbers in the 
space between the intima and adventiva of the vascular walls 
and thus narrow the lumen until a partial stasis of the red cor- 
puscles results. Masses of yellow pigment accumulate in the 
adventitious sheath among the the leucocytes, sometimes in con- 
siderable quantities. These haematoid granules have been 
frequently noticed. This yellow pigment which collects in the 
adventitious sheaths of the blood vessels and elsewhere is doubt- 
less derived from the red corpuscles, which are colorless in these 
cases. We are reminded of Muhlman's studies on the pigment- 
ary metamorphosis of red corpuscles in the Arachnoid.1 The 
yellow grains are found in the walls of the arachnoid vessels. 
They are not soluble in chlorform but, unlike fat, partially dis- 
solve in sulphuric and nitric acids. Tests with sulphide of. 
ammonia and potassium ferrocyanide demonstrate iron. The 
author supposes that the pigment formation is due to a state of 
irritation caused by pressure. They accumulate in the arachnoid 
because there the texture is so slight as to submit them to pres- 
sure. It might be supposed therefore, that the granules found 
so generally in the clogged capillaries of paralysis are due to a 
similar irritative cause. 
THE CORTEX. 
We may begin our examination by glancing at sections 
from the tip of the temporal lobe (middle convolution). The 
outer neuroglia layer differs little from that of the normal brain. 
A careful study shows, however, numerous so-called spider cells 
or scavengers, which here appear as multipolar bodies staining 
faintly and lying closely involved in the mesh-work of the neu- 
JZur Pigmentmetamorphose der rothen Blutkorperchen. Beobachtungen von 
der Arachnoides cerebralis. Virchow's Arch. (12) VI, 1. p. 160. Herrick, Pathology of General Paralysis. 
13 
roglia (Fig. 9, Plate B). Opinion differs greatly as to the nature 
of these bodies, but from the sections before us one might con- 
clude that they are essentially amoeboid and their form depends 
upon that of the interstices in which they may happen to lie. 
In the next succeding layer, that of small pyramids, the 
changes are not such as to attract the eye but we soon notice 
that a great number of the small pyramids have undergone more 
or less pigmentary degeneration. While their processes and 
form have altered little if any, small areas of degeneration are 
present in the protoplasm. Sometimes these areas are appar- 
ently but an extension of the normal pigmentation near the base 
and adjacent to the nucleus, but it quite as often happens that 
the area forms a rather sharply limited cyst in other parts of the 
cell. The pigmented areas refuse the stain and are recognized 
by their own brownish yellow color. Fig. 5, Plate B. is a cell 
from this region. In some cases the degenerated area causes 
a bulbous protrusion of the cell, yet the nucleus is not at all 
affected. In the third layer or region of medium pyramids the 
conditions are not much different but before one reaches the layer 
of large pyramids it appears that there has been a dispersion of 
granules which fill the whole field. It is the region of the ram- 
ification of small vessels. The larger radial vessels at this point 
give evidence of important morbid changes; the walls at first 
seem thickened but we soon see that the inner membrane or 
intima seems normal, but the outer or adventitious layer is 
gorged with leucocytes so that it occupies more space than the 
lumen. One frequent result is that the cavity is more or less 
occluded and the red corpuscles hence undergo degeneration. 
Their coloring matter collects among the white corpuscles form- 
ing haematoid masses. It seems improbable that this leaching is 
due to the reagents-in fact, this is a well-recognized pathologi- 
cal phenomenon. The smaller vessels are usually empty, as 
though by the cutting off of the source of supply. Fig. 8, Plate 
D, illustrates such a vessel as above described. See also Plate E. 
It will be remembered that Flemming1 has shown that in the 
1Ueber Theilung und Kernformen bei Leukocyten, etc. Areh. fUr mikr. 
Anatom, xxxvil. p 249. 14 
Pathological Bulletin. 
extravascular leucocytes in salamander multiplication is by 
mitosis or nucleary cell-division. Lowit attempted to distin- 
guish between erythroblastic and leucoblastic nuclei and claimed 
that mitosis occurs only in the erythroblasts, which are devoid 
of amoeboid movements. Flemming, however, finds that mito- 
sis is common in the amoeboid leucoblasts and thus agrees with 
Muller, Bezzozero and Newmann. The author thinks it proba- 
ble that fragmentating cells (i. e. amitotic elements) are in a 
state of decline and are incapable of reproduction. This may 
be compared with Frenzel's view that the cells reproducing by 
fragmentation are substituting and not constructive elements, as 
in the case of those cells in the mucous membrane which are to 
degenerate in the formation the mucous secretion. The nature 
of leucocyte proliferation in the brain should have careful study 
with modern methods. 
In the layer of large pyramids the degenerative process is 
more conspicuous by reason of the larger size of the elements 
but no more general or relatively extensive. In the radial fibres 
we encounter here and there a phenomenon of which we 
find no mention elsewhere. Long deeply staining nuclei, resem- 
bling in color the leucocyte or "granule" nuclei, but many times 
as long as wide lie in the course of the fibre and seem to occupy 
the sheath. This is probably different from the varicose condi- 
tion of the apex process sometimes encountered, Figs. 4, 5, 
Plate B. These bodies at times very closely resemble the nuclei 
of the intima of the vessels and must be carefully distinguished 
from these nuclei when greatly elongated in the finest capillar- 
ies. The color and appearance and the small diameter as well 
as the position of these bodies serve to prevent error. We in- 
cline to believe them characteristic of the degenerative condition 
as stated more in detail below. 
The innermost cortical layer, that containing multipolar 
cells, offers no noteworthy peculiarity. 
A typical motor region is found in No. 2, from the pre- 
central or ascending frontal convolution. Here the nests of 
very large pyramids with long processes are eminently charac- 
teristic. Fig. 13 of Plate B. gives a good idea of these cells Herrick, Pathology of General Paralysis. 
15 
which are generally, though by no means universally, degener- 
ate. 1 he apical processes do not seem to be degenerate in any 
case and the atrophy of the protoplasm and fatty pigmentary 
degeneration at the base are the most malign symptoms. The 
smaller pyramidal cells of the ectal part of the cortex are gener- 
ally intact. The usual alteration in the vessels occurs to a mod- 
erate extent. We do not encounter the enormous development 
of spider cells which Dr. Bevan Lewis considers characteristic 
of the disease. 
In the region of Broca ( Plate E, Fig. i, No. 6) we are 
dealing with a motor area and encounter chiefly fatty or pig- 
mentary degeneration of the cells. This change involves not 
only the deep pyramids but all the nerve cells to a greater or 
less extent. Figs. 2, 3, 7 and 12, Plate B., illustrate the vary- 
ing phases of this degeneration. In Fig. 12 the cells are 
slightly altered while in Fig. 3. the degeneration appears in vari- 
ous parts of the cell causing a certain amount of deformation. 
Sometimes it is one of the basal processes while in others the 
apical process is occupied by the yellowish granular material. The 
nucleus is scarcely ever implicated. No changes of importance 
can be detected in the neuroglia or nutritive elements. Rarely 
we detect a degenerative fiber containing the serpentine bodies 
described above. Usually where one of a "nest" of motor 
pyramids is altered all of the cells are involved. 
There seems to be no increase in the number of leucocy- 
tes about the injured pyramids-if anything, they are fewer 
than about the normal elements. There can be no doubt that 
these so-called "granules" are identical with those which 
under pathological conditions (congestion) pass through the 
vascular walls in such incredible numbers. It is a question of 
some importance to decide whether the proliferation of leuco- 
cytes take place within the vessels or at large within the brain 
substance, or whether the multiplication goes on in the usual 
sources and the accumulation in the perivascular spaces is due 
to a kind of retardation incident to impaired vitality of the 
brain. Our own observations thus far point to amitotic pro- 
liferation in the adventitions sheaths. 16 
Pathological Bulletin. 
In none of these sections do we find any extensive muli- 
plication of what Bevan Lewis calls the lymph-connective ele- 
ment. The pale corpuscles with flask-shaped faintly staining 
bodies are no more numerous than in the healthy brain. Oc- 
casionally the cell-body is shrunken, as a result of which the 
processes, which are originally very numerous, became more 
conspicuous. Golgi staining and our haematoxylin process 
seem to show that these cells are always supplied with an enor- 
mous system of processes whose terminal brushes often collect 
about blood vessels and other cells. 
We venture to quote somewhat at length from Bevan 
Lewis respecting the lymph-connective elements or spider cells, 
(scavenger cells.) 
"The cells which are usually called 'glia cells,' or what 
we have, in our anatomical section, alluded to as the 'flask- 
shaped elements' of the neuroglia, undergo a wondrous trans- 
formation, the real significance of which does not appear to have 
been hitherto appreciated. . . . These elements are 
small flask-shaped cells with a comparatively large nucleus at 
their greater extremity, which latter stains faintly with aniline- 
black, whilst the protoplasm of the cell itself remains unstained, 
and so delicate as to be recognized with difficulty in healthy 
states. Each has a connection by a delicate process with a 
neighboring blood vessel, and in frozen sections fresh examined, 
exhibits several branches so fragile and so excessively delicate, 
as to be seen only after a keen search, as they remain wholly 
unstained by reagents. In the morbid change to which we now 
allude, these flask-shaped cells enlarge very considerably into 
great amoeboid masses of protoplasm, often exhibiting subdivi- 
sion of the nucleus ; and, what is of great import, their proto- 
plasm now stains deeply with aniline, though not so intensely as 
their nuclei. From this extraordinary cell of protean form 
radiate on all sides numerous branching fibrils, forming an intri- 
cate and delicate network around it as a centre, all of which 
branches even to their most delicate subdivisions are readily 
stained by the same reagent. These cells have been termed 
Deiter's cells; they are all characterized by the presence of a Herrick, Pathology of General Paralysis. 
17 
vascular process; but well prepared specimens show not one, 
but often several, such processes distinguished by their greater 
diameter, their deep staining, and their termination in a nucle- 
ated mass of protoplasm upon the walls of a blood vessel." 
The protoplasm of these cells is said to stain in abnormal 
states but not in normal, because in the former case there is an 
unnaturally increased vitality. They are said to spread through- 
out the neuroglia framework and multiply by nucleary subdi- 
vision and segmentation of the cell mass. The last stage in the 
development of these bodies is one of fibrillation in which the 
cell is exhausted by ramifying into innumerable fibrillary pro- 
cesses. As elsewhere stated, we are inclined to believe that 
these are truly nervous elements which become more accessible 
to stain as they shrivel. Proper methods demonstate richly 
branching processes even during health. 
In the region of the hippocampus the evidences of morbid 
activity are fewer than in cortical motor areas, yet there are re- 
gions where profound alterations have taken place. There are 
many cases where the pigment degeneration is discoverable but 
the process has not gone far enough to implicate a large part of 
the protoplasm. The degeneration manifests itself here in the 
alteration of the fibres. These are large and distinct and even in 
our somewhat imperfect specimens the apical processes are seen 
to be shriveled and altered. One evidence of the change is 
seen in the remarkable vermiform or rod-like granules which lie 
upon or within the process or in the more distant part of the 
fibres. These are well-shown on Plate D Fig. 6 and Fig. 7 
These vary from short ovoid to rod-shaped or long worm- 
like. It has not been possible to find a description of these 
bodies but we venture to suggest that they are the elongated 
nuclei of leucocytes or scavengers which have penetrated the 
sheath in pursuit of the decomposing protoplasm of the fibre. 
The reasons for this asumption are, 1. that the least modified of 
these bodies closely resemble the phagocytes, 2. no other 
source for these bodies is suggested, 3. analogy suggests 
that some means of disposing of the obviously decomposing pro- 
cesses, where as large as in this case, must be found. 18 
Pathological Bulletin. 
Sections have been made from the most caudal part of the 
occipital lobe and show that, as usual, the purely sensory regions 
are not implicated. The cortex is almost wholly unaltered and, 
whereas the sections in the motor regions stained slowly and 
imperfectly with ordinary reagents, here the stain is well differ- 
entiated and uniformly operative. 
THE BASAL REGIONS. 
The histological changes of general paralysis are typically, 
if not exclusively, those of the cortex, and particularly of its 
cells. The references to the degenerative effects in the great 
ganglia of the axial portion of the brain are, so far as my obser- 
vation has gone, very scanty. Mendel says: "Aside from the 
described changes, which occur chiefly in the cortex and adja- 
cent parts of the white substance, which may, however, occur, 
though to much less extent, in the large ganglia (an atrophic con- 
dition is here developed only after paralysis of long duration 
and extensive laming), there may be observed the greatest va- 
riety of focal lesions in paralytics." 
The peduncles have been found to be degenerated in a few 
cases (Huguenin), in one case the gray degeneration of the dor- 
sal fasciculi could be traced from thalamus to the cauda equina 
and in the motor peduncles and pyramids, extended to the 
oculomotor region. 
A section through the very cephalic portion of the thala- 
mus shows that its small cells are but slightly affected while the 
somewhat larger multipolar cells scattered in the striatum at the 
same level are thoroughly implicated. Passing caudad, the thal- 
amus retains the same general character though increasing to 
form a large quandrangular area {Fig. i a, Plate D.}. Around 
the margins, near the peduncular fibres there are small multipolar 
cells which are greatly altered. These cells are like those fig- 
ured on Plate D, figure 5, which are from x in Fig. 1 of the 
same plate. They are larger than the cells of the thalamus 
proper. 
For a study of the striatum we may select a portion of a 
section corresponding to "B" of the Pitres-Nothnagel's series Herrick, Pathology of General Paralysis. 
19 
(Hirt's Diseases of the Brain, p. 197). Ectad of the internal 
capsule, which evinces no alteration that can be detected by 
the means here employed, is the head of the caudatum, consist- 
ing of a stroma of densely nucleated matter and sporadic fibre 
bundles. There is almost absolutely no alteration in the sub- 
stance of either caudatum or lenticulare at this level. We may 
add that the present tendency to attribute important psychical 
functions to the striatum has as little anatomical foundation as 
psychological significance. By far the largest part of the striata 
is composed of sporadic bundles from the capsule. The vessels 
of the striatum are nearly normal. The lesion is decidedly cor- 
tical. A series of sections through the peduncular region is of 
special interest as showing that in this segment the degenera- 
tion is limited to the motor projection system. The cells of 
the tectum and niduli of the cephalic quadrigemina, as well as 
of the ruber, are scarcely modified at all. The nidulus of the 
oculo-motor is quite unaffected. There are slight changes in the 
pulvinar and other niduli of the thalamus, but when we turn to 
the vicinity of the motor peduncle fibres we encounter most con- 
spicuous evidence of degeneration. The large and complicated 
nidulus niger, including the most remarkable cells of the mesen- 
cephalon is almost completely altered. These cells, which hug 
the ental margin of the peduncles and form the boundary be- 
tween tegmentum and crusta are not only of enormous size, but 
by reason of the great extent of their processes they stand out 
among the elements of the brain. In a series of papers1 the au- 
thor has endeavored to follow the homologies of the nidulus 
throughout the veretebrate phylum. It has proven possible to 
trace the relation between the pecular cells, which are not easily 
mistaken for any other cells in the brain, from fishes to mammals. 
The development of the nidulus niger or Soemmering's nidulus 
stands in close ratio with that of the cerebellum. In fishes the 
ventral peduncular fibres, which can hardly be other than the 
1 Contributions to the Morphology of the Brain of Bony Fishes, Journ. 
Comp. Neurology, Vol. II. Notes upon the Histology of the Central Nervous 
System of Vertebrates. Festschrift zum siebenzigsten Geburtstags Leuckart's; 
Anat. Anzeiger, VII, 13, 14. 20 
Pathological Bulletin. 
motor tracts, come into intimate association with cells which in 
form and relations seem to be homologous with the niger cells 
(i. e., cells in hypoaria). The cerebellar tract also enters into 
relation with this nidulus. Following this clue we trace the 
same relation in all the higher groups. It seems safe to affirm 
that the site of motor association with the cerebellum is in this 
cell-clustre. It need not surprise us that in a disease which is 
due primarily to a disturbance of the cortex and notably the 
motor-cortex, the projection centres of the centrifugal tracts 
should be especially injured. It seems to amount to an inci- 
dental confirmation of our anatomical observation and physio- 
logical theory that the nidulus niger is the only region of the 
mesencephalon in which pronounced indications of degeneration 
are observed. The nidulus extends from the exit of the third 
nerve to the point where the peduncles enter the striatum and 
throughout its entire extent nearly every cell is more or less 
completely degenerate. In some cases the whole cell body is 
reduced to a vague patch of yellow granules, while in others 
bands or stripes of unaltered protoplasm remain. Frequently 
the incipient stages of decay are seen in a deep pigmentation 
near the nucleus or one process only is disorganized. The char- 
acteristic features of these degenerate cells are best gathered from 
the figures. 
Plate D, Fig. g, illustrates a niger cell far cephalad near y 
in Fig. i. It well shows the two axis-cylinders of a switch cell. 
Fig. 2, is a portion of the same field with cells in various stages 
of degeneration. One cell especially illustrates the rare condi- 
tion where a bulbous swelling occurs upon a process. In some 
cases the nucleus itself has suffered partial destruction. Fig. 
contains two unaltered cells giving a good idea of the various 
processes though the finer ramifications of the protoplasmic pro- 
cesses are not bought out. Figs, g and of Plate C, illus- 
trate the changes seen in the same nidulus at the level of the 
third nidulus. 
Figs, i are 2 and portions of transverse sections at the 
level of the pulvinar and third nidulus respectively, for orienta- Herrick, Pathology of General Paralysis. 
21 
tion. Both are figures of actual sections from which Figs, g 
and 4 were drawn. 
THE CEREBELLUM. 
The cerebellum, although somewhat isolated from the real 
centre of morbid activity, might be expected to be involved 
with other portions of the brain. The vessels of the meninges 
are only slightly modified and the intrinsic capillaries not at all. 
The only way in which the extensive changes in the basal gang- 
lia of the fore-brain could react indirectly on the cerebellar 
structures would seem to be through an atrophy of disuse. 
While the ganglia in the motor tracts bear unmistakable evi- 
dence of extreme degeneration it would seem quite improbable 
that an extensive atrophy should have had time to develop itself. 
It will be remembered that (in our view) the axis cylinders of 
the Purkinje cells passes directly into the restiformia, while the 
peripheral or protoplasmic processes afford opportunity for asso- 
ciation by contiguity with the fibres of the mid-peduncles of the 
cerebellum which on their part may connect with the cells of the 
basal ganglia. 
Since, then, the relations are very indirect, we should not 
be surprised to find the cerebellum normal in the absence of irri- 
tating causes in the organ itself. The cerebellum can hardly be 
subject to as rapid alterations in blood pressure as the cerebrum 
and contains within itself a large stock of reserve nutrient ma- 
terial. Careful examination reveals only a few cases where the 
cells of Purkinje have some traces of the fatty degeneration 
seen elsewhere (Fig. g, Plate C.) Most of the lobules are nor- 
mal, but occasionally there is one of the folia in which there is 
extensive atrophy of the cells of Purkinje. Fig. 4., Plate E, il- 
lustrates such an instance. In the sections wherein ordinarily a 
score or more of cells should stand, only one or two isolated cells 
remain. There is no notable degeneration in the other struc- 
tures, but the space which should contain these bodies is empty 
or contains shriveled remnants. In these cases it might appear 
that the change was the result of early stages of the disease. 
In the unaltered Purkinje's the structure is well preserved 22 
Pathological Bulletin. 
{Fig. g, Plate E,) and the adjacent elements are intact. Al- 
though this is perhaps not the place to discuss morphological 
questions we may call attention to the fact that the radial ele- 
ments with fusiform cellular dilatations {Fig. j a') are apparently 
remnants of the spongioblast system, as may be gathered by a 
comparison with lower vertebrates. 
THE MEDULLA. 
It is unfortunate for our purpose that the medulla of the 
specimen was ruined during removal so that the important ques- 
tion as to the subordinate centres along the motor columns and 
particularly the condition of the vaso-motor centres remain un- 
examined. 
THE CORD. 
For a similar reason the cervical cord is not in a condition 
to report upon in detail. A number of sections from the cer- 
vical region show that the ventral cornua of the gray matter is 
very largely involved. The large ganglion cells are in some 
cases intact, but generally are more or less affected by the fatty 
degeneration. In some cases the entire cell is reduced to a 
mere sac filled with granules of a honey yellow color. These 
stages are illustrated in Fig. 2} Plate E. 
No serious affection of the meninges or blood vessel is ob- 
vious from the specimen. If there is any secondary degenera- 
tion the only suggestion offered by our sections is a suffused 
condition of the crossed pyramidal tract of the lateral column. 
In the same region there is some gorgement of vessels and nu- 
cleary proliferation. 
DESCRIPTION OF FIGURES. 
PLATE A. 
Lateral view of the right side of the brain drawn from the fresh specimen 
corrected by reference to the model subsequently prepared. Herrick, Pathology of General Paralysis. 
23 
PLATE B. 
Fig. i. Pyramidal cortical cell and portion of a capillary vessel from fron- 
tal lobe (Plate E, Fig. I, No. 4. The cell is but slighly altered. The vessel is 
in the first stage of degeneration. The granules are multiplying and escaping 
into the perivascular space. 
Fig. 2. A group of cells from the layer of deep pyramids in Broca's region. 
An enormous cyst-like mass of pigmentary degeneration in one of the motor 
cells. 
Fig. j. Other cases of degenerated cells from Broca's region. 
Fig. 4. A case of varicose alteration of the apical process. 
Fig. 5. Similar instance from temporal lobe (No. 1). 
Fig. 6. Incipient degeneration in a cell of the temporal lobe. 
Fig. 7. Striking instance of pigmentary degeneration in Broca's region. 
Fig. 8. Incipient degeneration of cell from frontal lobe. 
Fig. 9. So-called scavenger cells from temporal lobe. The tangential 
fibres form the upper margin of the section. 
Fig. 10. Deep pyramid of frontal lobe. 
Fig. 11. Superficial pyramid of the same region. 
Fig. 12. Three slightly altered large pyramids of Broca's region. The 
sole indication of the lesion is an increase in the pigment. 
Fig. T3- Large Pyramids from Precentral convolution. (No. 2.) 
PLATE C. 
Fig. 1. Part of a transection through the cephalic corpora quadrigemina 
and pulvinar. 
Fig. 2. Part of a similar section through the roots of the third nerve. 
Figs, 3, 4. Degenerating cells of the nidulus niger from the sections above 
indicated. 
AXf 5. Slightly altered cells of Purkinje from the cerebellar area shown 
in Fig. 6. 
Fig. 6. Apparently normal cerebellar cortex. Compare with Fig. 4, 
Plate E. 
PLATE D. 
Fig. i. Transection of left hemisphere through the thalamus and hippo- 
camp. 
Fig. 2. Forward extension of the niger beneath the thalamus at y, Fig. i. 24 
Pathological Bulletin. 
Fig. 3. Uninjured cells. 
Fig. 4. Similar normal cells from the niger farther caudad. 
Fig. 3. Smaller cells from dorsal region of the peduncles (x, Fig. 1.) 
Figs. 6, 7. Cells from hippocamp showing certain amount of pigmentary 
degeneration and vermiform nuclei apparently attacking the fibres. 
Fig. 8. A typical casQ. of vascular degeneration. Nuclei accumulating in 
the adventiva and stasis of red corpuscles. 
PLATE E. 
Fig. i. Diagram of front of left hemisphere to locate regions referred to 
in text. The shaded areas are portions actually sectioned. 
Fig. 2. Cells from ventral cornu of the cord. 
Fig. 3. Normal cells of Purkinje, a, spongioblast nuclei. 
Fig. 4. Portion of cerebellar cortex where the cells have degenerated. 
Fig. 3. Degenerate cells from temporal lobe. 
Fig. 6. Blood vessel where the intima has separated from the adventiva- 
The latter filled with corpuscles. 
Fig. 7. Diseased cortex cells. Journal of Comparative Neurology, Vol. III. plate a. Bulletin State Hospital for Insane, No. i. 
PLATE B. Bulletin State Hospital for Insane, No. i. 
PLATE C. Journal of Comparative Neurology, Vol. III. 
PLATE D. Bulletin State Hospital for Insane, No. i. 
PLATE E.