STUDIES ON THE LESIONS PRODUCED BY THE 
ACTION OF CERTAIN POISONS ON 
THE NERVE-CELL. 
[From the Anatomical Laboratory of the Johns Hopkins University.] 
Part II.—Experimental Lesions Produced by the Action of Dog's 
Serum on the Cortical Nerve-cell of the Rabbit's Brain. 
(preliminary paper.) 
BY 
HENRY J. BERKLEY, M.D., 
OF BALTIMORE, MD. 
FROM 
THE MEDICAL NEWS, 
August 31, 1895. [Reprinted from The Medical News, August 31, 1895.] 
STUDIES ON THE LESIONS PRODUCED BY 
THE ACTION OF CERTAIN POISONS ON 
THE NER If E- CELL. 
[From the Anatomical Laboratory of the Johns Hopkins 
University.] 
Part II.—Experimental Lesions Produced by the Action of Dog's 
Serum on the Cortical Nerve-cell of the Rabbit's Brain. 
(PRELIMINARY paper.) 
BY HENRY J. BERKLEY, M.D., 
OF BALTIMORE, MD. 
The interest that has recently been taken in the 
action of a number of soluble bacterial poisons pro- 
duced in the course of certain infectious diseases, 
and capable of inducing various epiphenomena from 
their effect upon the nervous system, is well attested 
by numerous articles from the pens of authors in the 
four principal languages of the civilized world. 
The endeavor of the majority of these workers has 
been to discover in the corpus of the nerve-cell cer- 
tain definite changes by means of selective stains, 
rather than to take up the several members of the 
neuron and consider them separately, and, indeed, 
this has only recently become possible. 
While it is possibly stretching a point to consider 
blood-serum in the light of a bacterial poison, its 
action upon the tissues is not dissimilar, as may be 
seen from the results of the examination of other 
organs than the cerebrum from rabbits dying of 2 
chronic serum-poisoning, and it is highly probable 
that we shall eventually find in every person dying 
after the long-continued action of soluble poisons, 
whether bacterial or chemic, a class of lesions of 
the neuron similar to those described in this com- 
munication. 
In the pathologic material from the autopsy table 
we are sadly hampered by a multitude of post- 
mortem and other changes, which, though of great 
moment, are imperfectly known. Therefore, ex- 
perimental material, under full control from the 
moment the inoculation is made, through the vari- 
ous stages of the experiment down to fixation and 
the staining and mounting of the sections, is of the 
utmost value in establishing a precedent for a simi- 
lar class of lesions in the human being, especially 
as there are no wide anatomic differences between 
the nerve-cell of the animals used and those of man. 
The material for the purposes of the study is at 
the present time small in amount but as it is for the 
moment impossible to add to it, and as the lesions 
in all the sections have been very constant, and of 
a well-defined though new type, I have concluded 
to utilize what I have on hand, and add to the re- 
sults at a later date. I shall, therefore, confine 
myself to a description of the histologic changes 
found, without indulging in speculative conclusions, 
an intention for which apology is hardly needed. 
It is to my mind proved by the destructive action 
of poisons on the nerve cell of the cortex that it 
only requires the long-continued action of almost 
any soluble toxin to cause destructive effects on 
the neuron, and that these do not call for the pres- 3 
ence of a micro-organism. This principle may be 
more clearly demonstrated in subsequent papers, 
and it will probably eventually be shown that poi- 
sons that are supposed to be limited in their action 
are probably universal nerve-poisons, and that their 
continued action results in an extensive degradation 
of the entire nervous system, if only a sufficient 
length of time be allowed them. 
In the winter of 1893, Dr. Simon Flexner, of the 
Pathological Laboratory of Johns Hopkins Hospital, 
began a series of experiments upon the action 
upon rabbits of blood-serum obtained from man and 
the dog. These researches have been continued, 
although an outline of the pathologic changes 
found after the inoculations, in connection with a 
series of other studies, has already been published.1 
Briefly, Flexner found that injections of serum of 
1.5 per cent, of the bodily weight of the animal ex- 
perimented upon were usually fatal, death occur- 
ring either immediately or after the lapse of ten 
or twelve hours. Quantities equal to 1 per cent, 
of the bodily weight caused profound disturbances, 
including hemoglobinuria and albuminuria, less 
commonly anuria, and in a few instances imme- 
diate death. When death followed at once it was 
usual to find thrombi in the right side of the heart, 
which now and then extended into the pulmonary 
artery and its branches. Cases in which the death 
of the animal was delayed for a time were of espe • 
cial interest, as they showed well-marked lesions 
resembling in many ways the changes described in 
1 “ The Pathologic Changes Caused by Certain So-called Tox- 
albumins.’’ The Medical News, Aug. 4, 1894, p. 116. 4 
connection with the toxalbumins of diphtheria, 
ricin, and abrin. 
The organs studied were the spleen, liver, kid- 
neys, and lymph-glands. In the acute cases the 
spleen showed a tolerably rich fragmentation of 
nuclei situated especially in the Malpighian bodies ; 
the liver, certain foci of cellular necrosis; while the 
renal epithelium was degenerated and many casts 
blocked the kidney-tubules. Very extensive lesions 
were found in one animal that died on the thir- 
teenth day. The microscopic appearances were 
those of chronic interstitial processes in the liver 
and kidney. In the latter organ the tubules were 
in places atrophied and surrounded by a new 
growth of connective tissue ; in other places the 
tubules were dilated and their epithelial lining de- 
generated. In the liver the chronic changes were 
exceedingly well marked, and were an accurate 
reproduction of cirrhosis in the human being. Areas 
of newly formed or forming connective tissue pro- 
ceeded from the portal spaces and from the capsule; 
newly formed bile-ducts were numerous, but what 
was of especial moment was the association with 
these changes of another process, viz., acute degen- 
erative changes in the liver-substance, which were 
often distinctly the starting-places of the sclerosis. 
In the spleen masses of fibrous tissue were found. 
These changes show that the damage the serum is 
capable of doing is not limited to the corpuscular 
elements of the blood, for the tissue-cells also are 
not indifferent to its action. 
From a later series of experiments than those just 
referred to, Dr. Flexner very kindly placed at my 5 
disposal the cerebra of several of the rabbits, in order 
to enable me to determine if the nerve-cells suffered 
from the action of the serum in a manner equivalent 
to those of the viscera mentioned. Unfortunately 
for our closer knowledge of the cerebral cells, these 
elements do not show mitotic figures, nuclear frag- 
mentation, and coagulation-necrosis in the same 
manner as the liver-cells, but with our best stains, 
whether chemic combinations with the cellular sub- 
stance or simple dyes, they are eminently stubborn 
to microscopic analysis ; and from the reaction of 
the protoplasm to the dyes we can demonstrate in 
cells we perforce know must be diseased only indefi- 
nite alterations in the amount of absorption of the 
dye by the protoplasm, especially of the chromo- 
philic particles, and most uncommonly any definite 
changes in the nucleus or nucleolus. These difficul- 
ties in obtaining accurate results from minor 
changes in the nerve-cell probably arise from the 
circumstance that the nerve-cells are completed 
elements, incapable of regeneration, and only show 
alterations of a pronouncedly degenerative type. 
The material for this study has to this time been 
the brains of three rabbits from parts of two series 
of serum experiments, and, so far as the lesions of 
the cortical cells were determined, they were con- 
stant and identical in all the animals, though vary- 
ing in intensity, seemingly according to the sever- 
ity of the poisoning, as rabbit No. 2, first series a, 
which died from the result of an injection and 
not from the long-continued poisoning the others 
underwent, exhibited vastly larger numbers of 
normal cells than its companions in the investiga- 6 
tion. It will be noticed in the table that this rab- 
bit lost only about two-hundred grams in weight, 
and, accordingly, was not so greatly emaciated as 
the others. It is, at present, impossible to deter- 
mine exactly what part the denutrition of the tissues 
plays in the production of the lesions of the nerve- 
cell, but I can hardly doubt that it is very second- 
ary to the direct influence of the poison upon the 
cell, for in human alcoholics that show no emacia- 
tion the same kind of lesions are found, varying 
somewhat in intensity. 
A synopsis of the histories of the rabbits comprising 
the basis of this study is given in the accompanying 
table. 
Methods of Preparation and Staining. 
The methods pursued in the preparation of the 
cerebral tissues for this investigation were similar 
to those made use of in Part 1/ of these studies, 
namely, fixing the tissues in alcohol and in Muller’s 
fluid, and after treatment with various anilins, 
hematoxylin, and silver-staining, according to the 
silver phospho-molybdate formula, as already given. 
The control-preparations were obtained from the 
cerebra of two young but full-grown rabbits, treated 
exactly according to the same formulae for the fixing 
and staining, kept for the same length of time in the 
hardening media, and stained exactly by the same 
procedure as the serum-brains, often running the 
two together in the same jars. 
1 Fart I, “ Experimental lesions Produced by the Action of 
Absolute Ethyl-alcohol on the Nerve-cells of the Rabbit's Brain," 
will appear in the autumn number of Brain. Number. 
Age. 
Weight at 
beginning of 
experiment. 
Begun 
inocula- 
tions. 
Quantity • 
injected. 
Frequency 
of inocu- 
lation. 
Date 
of 
death. 
Weight 
at 
death. 
Clinical 
cause of 
death. 
Gross anatomic 
lesions. 
Remarks. 
I 
Series 2, b. 
Adult. 
1700 g. 
Nov.22 
1894 
6 c.cm. 
increased to 
18 c.cm. 
Intervals 
of 2 w’ks. 
Apr. 8 
1895 
1200 g. 
Exhaus- 
tion. 
Great emaciation; 
no visible lesions. 
There were no well marked men- 
ingeal changes in any of the 
rabbits. 
2 
Series 1, a. 
Adult. 
I7°0 g. 
Nov. 6 
1894 
6 c.cm. 
increased to 
18 c.cm. 
Intervals 
of 2 w’ks. 
May s 
1895 
1500 g- 
Over- 
dose of 
serum. 
Thrombi in heart 
and brain. 
Injections of 12 c.cm. were fatal 
in control-rabbits. 
Series i, b. 
Adult. 
1800 g. 
Nov. 6 
1894 
6 c.cm. 
increased to 
18 c.cm. 
Intervals 
of 2 w’ks. 
May 31 
1895 
130° g. 
Exhaus- 
tion. 
Great emaciation; 
no gross lesions. 
Rabbit No. 2 died suddenly after 
an injection of serum. 
Serum Rabbit Series. 8 
As mentioned in the first section of these studies, 
there are upon the dendronsof the nerve-cells of the 
cortex a minimal number of thickenings or varicosi- 
ties. The majority of these occur at the forkings 
of the dendritic branches, and rarely indeed is one 
to be found in the course of any of the finer 
branches in the normal brain. In the course of the 
axis-cylinder there are also knots of somewhat 
greater frequency, which begin at a variable interval 
from the cellular body, and continue through the 
entire intra-cortical course of the axon. Occasional 
varicosities of the dendron must, therefore, be held 
to be normal, the same holding good for the axon, 
although in the latter they are present in greater 
frequency. Since Coella, Greppin, Andriezen, and 
a few others have found in human brains, princi- 
pally those of paralytic dements, an increased num- 
ber of swellings upon the dendrons, the subject of 
these varicosities has attracted some little attention. 
Flatau' has quite recently discussed them at some 
length, and has arrived at the conclusion that they 
are natural. 
It is quite possible to imagine that normal brains 
have a varying number of varicosities upon their 
dendrons, but when they increase vastly in size and 
occupy the whole dendron, they must be held to be 
abnormal, especially when they present a size that 
is incompatible with anything in the normal con- 
trol-preparations ; and the entire cell, with the ex- 
ception of the axon, frequently shows evident signs 
of the presence of a destructive process. Not only 
are these abnormal swellings of great frequency on 
1 Archiv fiir Mikrockop. Anatomic, May, 1895. 9 
the finer branches and along the stems of the pyram- 
idal nerve-cells, but it may readily be demon- 
strated that the very varicosities normally present, 
particularly the enlargements at the branchings of 
the dendrons, take on this alterative process, and in 
themselves became tumefied. Furthermore, we 
have one certain sign of dendritic degeneration in 
the pyramidal and some other nerve-cells that 
seems to have entirely escaped the attention, not 
only of the criticisers of the value of the probable 
degeneration, but also of its exponents. I refer to 
the disappearance of the gemmules or lateral buds 
upon the branches of the dendrites, which takes 
place whenever the tumefactive process is at all 
advanced, or even occurs coequally with this. 
I have elsewhere written more fully of the gem- 
mule and its significance histologically, and in 
certain forms of dementia, and it suffices now to 
give a short anatomic description of one very in- 
teresting part of certain of the most important 
of the nerve-cells, which for some unexplained rea- 
son, possibly from defective staining, has hitherto 
received but little attention. The gemmule, in its 
most developed state, is found only on the dendrites 
of two classes of nerve-cells, the pyramidal or psy- 
chic cells of the cerebral cortex, and the Purkinje 
cells of the cerebellar cortex. Histologic differ- 
ences in the appearance of the gemmules are very 
apparent in these two varieties of cells. With the 
pyramidal bodies they present very much the ap- 
pearance of a thin pin with a rounded head, 
having its sharpened point stuck into the proto- 
plasmic substance along the edges of the dendrons, 10 
both the ascending and basal of the cells. They 
are arranged with considerable regularity along the 
thicker protoplasmic branches, and at a rectangle 
with the stem of the dendrite. 
On the finer dendrites the intervals between the 
gemmules are slightly increased, and while preserv- 
ing the same form as on the thicker branches they 
are slightly longer, and have less of the rectangular 
disposition. On the branches of the Purkinje cell 
the gemmules are very numerous and much more 
closely set together than on those of the pyramidal 
cell, and they give to the neuron a furry apj>ear- 
ance. Besides these inherent characteristics, they 
begin by a broad base, do not increase in size as 
they extend outward, and terminate not in a rounded 
knob, but in a flattened ending that is no larger than 
the proximal portion of the stem. Here and there 
between the others single ones are found, similar in 
appearance to those of the cortical cells. 
The function of the gemmule probably is to re- 
ceive nerve-impulses from the endings of the numer- 
ous terminal nerve-fibers that seem almost to touch 
them, and to carry these impressions to the dendrite, 
and by its medium on to the cell-body. Differences in 
the function of the gemmule of the pyramidal and 
Purkinje cell are probable. 
Histology of the Alcohol-hardeneij 
Serum specimens. 
The staining of the sections for this portion of the 
study was by Nissl’s methylene-blue and magenta, 
and hematoxylin-eosin. The only noticeable dif- 
ference between the several brains was that in No. 11 
2 the perivascular spaces contained a considerable 
number of polynuclear leukocytes, while in the 
other specimens these corpuscular bodies were 
absent. 
The larger and medium-sized arteries have abso- 
lutely no sign of alteration in their several coats. 
The intermediary vessels are not at all prominent; 
their sheaths are normal; and the perivascular 
spaces, while distinct, are not dilated, and contain 
no foci of round cell aggregations and no hema- 
toidin debris. The capillaries and veins are normal. 
The endothelium of the vessels shows no trace of 
swelling or other abnormality. 
The staining of the nerve-elements by the Nissl 
methods was made as intense as possible, and the 
decoloration not allowed to proceed quite to the 
usual point, in order to leave the protoplasmic pro- 
cesses stained to their fullest extent. The nuclei of 
the nerve-cells do not seem to be shrunken or irreg- 
ular in contour. Few of them are of other than 
the mono-nucleolar variety. This nucleolus is 
smooth, lies toward the center of the nuclear ring, 
and shows no alteration in its capability for the 
absorption of the anilin. 
Changes in the protoplasm of the corpora of the 
cells are somewhat indefinite. The protoplasm 
takes the anilin stain well, but the chromophilic 
particles are not well defined, and the intervening 
spaces between them seem to be occupied with more 
of the fine granules than are present in the control- 
slides. No stress can be placed on these indefinite 
changes. 
A very few of the pyramidal cells contain vacu- 12 
oles, but not even as many as three in a section. 
Seldom is there any appreciable shrinkage in the 
protoplasmic body ascertainable. The protoplasmic 
arms of the cells are very finely granular. In some 
of them small knots are to be seen, the swelling 
being recognizable from the absorption of a greater 
quantity of the dye than is present in the por- 
tions more distant from and more proximal to the 
cell-body. In the swelling the fine granules become 
less distinct than elsewhere. 
In the cerebellum there is nothing noticeable in 
the cells of the granular and molecular layers. 
A few of the Purkinje cells are vacuolated. 
Histology of the Muller’s Fluid-hardened 
Specimens. 
The staining of these sections was solely by the 
silver phospho-molybdate method. Between Brains 
i and 3 there were no microscopic differences 
of moment. Brain No. 2 showed a slighter degree 
of degenerative changes in the neurons than the 
others, and was especially interesting from the fact 
that the degenerated could always be found inter- 
mingled with approximately normal cells, affording 
an opportunity for an accurate comparison between 
the different elements. This brain was also remark- 
able for the beautiful staining of the nerve-elements 
of all the layers, which were exhibited in as jierfect 
a manner as can ever be obtained in silver-prepara- 
tions, and the sections were not disfigured by the 
presence of precipitate, even the external margins 
being free. 
The lesions found in all the cerebra were closely 13 
allied to those found in the alcoholic brains that 
formed the basis of the first study. Cells of all layers 
were involved in the destructive process, the pyram- 
idal of all varieties in the first order, then the 
deeper-lying elements, finally those of the extreme 
outer edge of the second layer and the elements of 
the molecular lamina. 
A view of a section under low enlargement shows 
that the primary processes of many of the pyramidal 
cells no longer reach into the outer portions of the 
molecular lamina. Their finer dendritic branches 
have disappeared, while the thicker ones are filled 
with a multitude of coarser and finer knots, scattered 
with some regularity along the line of the stem. On 
the other hand, the thick intra-capsular portions of 
the dendrites have not become diseased in a similar 
manner, but apparently retain their integrity in so 
far that they are not altered in appearance by coarser 
changes, and seldom does the body of the cell pre- 
sent aught but its even, rounded contour. The 
basal processes are often likewise shortened, and 
show the knotty growths upon them like their 
ascending fellows. 
Not every cell presents a similar degree of altera- 
tion, and according to the degree of involvement 
they may be divided into three classes : Cells in 
which the process is beginning ; those in which it 
is moderately advanced ; those in which the den- 
drons are very much degenerated. The normal 
cells in Brains i and 3 were comparatively infre- 
quent ; in No. 2, on the contrary, more that two- 
thirds of the stained cells were normal. 
As the degenerative process is of similar charac- 14 
ter among all the classes of cells, we have taken the 
most prominent type, the pyramidal cells, as the 
criterion of the whole, as they are very much easier 
to study than the other, and have a definite size 
and anatomic characteristics, as well as stain con- 
stantly. 
Class A, Cells Slightly Involved in the 
Alteration. 
High up in the molecular layer we find upon the 
finest branches of the dendrons of the pyramidal 
cells, especially those of the long apical-process 
variety, a few tumefactions of either rounded or 
elongated form in the course of the stem. These 
tumefactions are deeply stained by the silver-salt, 
are smooth, and have few or no gemmules attached 
to their sides, or, when these are still present, there 
are perceptible differences in the tingeing with the 
silver-salt that indicate an alteration in their struc- 
ture. Both nearer the cellular body and dislally 
from the swelling, the dendrite appears to be j>er- 
fectly normal, the staining is good, and the pin-like 
lateral buds are numerous. In these neurons the 
coarser branches and the corpus of the cell are 
undisturbed by any alteration apparent to the micro- 
scopic examination, and, indeed, the slight swellings 
on the finest twigs would occasion but slight com- 
ment were no other cells more deeply involved. 
Class B, Cells Moderately Involved by the 
Degeneration. 
This type is the most numerous of all. The tume- 
factions before present only on the finest dendritic 15 
Fig. r. 
Pyramidal cell from the mid-portion of the second cellular layer 
of the rabbit's brain, showing commencing tumefactions of the 
protoplasm of the finest apical dendrites, and denudation of the 
gemmules at the points of swelling. At the uppermost forkings of 
the ascending dendron a normal enlargement of the protoplasm 
is seen, which is covered with gemmules. Ax., axon. 16 
branches now extend throughout the entire path of 
the stems of the apical and basal processes, reaching 
up or down to their intra-capsular portion, and many 
of the finest branches are no longer stained, and are 
apparently totally degenerated, having been par- 
tially or totally removed. The number of the swelling 
varies greatly in the different involved cells. Usually 
the dendrons have a large number of small thicken- 
ings alongtheir course, and present a true moniliform 
appearance. Less commonly there are only a few 
of larger size, but the result to the nerve-process 
is the same. These large-sized swellings are pecu- 
liarly frequent at the forkings of the branches of the 
apical dendrons, where there is normally a thicken- 
ing of the protoplasm. Rarely one meets with 
dendrons in which the smaller swellings are so numer- 
ous that they are coalesced, and only are noticeably 
different from the normal dendron by the irregu- 
larity in their contour and the loss of the lateral 
buds. In all the varieties there is an absolute loss 
of the gemmules on the dendritic processes, which 
eventually proceeds to a complete stripping of the 
dendron of all its fine rectangular pin-like pro- 
cesses. This denudation of the gemmule varies 
considerably on the different dendrons according 
to the number and advancement of the swellings. 
When the stem has only a few tumefactions the 
intervening spaces usually retain some of the buds, 
but when the swellings are numerous or very large 
they progressively disappear, until in a very large 
number of instances not only the finest branches 
are stripped of them, but the thicker portions are 
equally bare. 17 
Following the swelling and loss of the lateral 
buds comes a contraction of the protoplasm of the 
dendritic twigs, especially that portion not involved 
in the swelling, though these also eventually atrophy. 
In the spaces between the swellings, as the process 
advances, the diameter of the branch grows less and 
less until it is reduced to a mere knotted thread. 
Fig. 2. 
A cell of different form from the same region of the cortex, 
showing an increased number of swellings and greater loss of 
gemmules. 
Then comes a time when there is a breaking up 
of the continuity of the twig. The finest branches 
fall off from the thicker stems, and are finally 
absorbed, the neuron now being reduced to the 
corpus of the cell, with the stumpy tumefied re- 
mains of the thicker dendrons attached to it. 18 
I wish particularly to draw attention to the loss 
of the finest branches of the dendrites within the 
limits of the molecular layer, a region of the utmost 
importance in the physiologic economy of the cor 
tex. Here the branches of the dendrons, by means 
of their gemmules, come into contiguity with the 
terminations of the nerve-fibers and end-apparatus 
of all descriptions belonging to the several classes 
of nerve-fibers, tending thitherward from the inte- 
rior regions of the cortex—fibers from the cord and 
opposite hemisphere, fibers from the fusiform and 
other cells of the lowermost layers of cortical cells, 
collaterals from the pyramidal cells, also to some ex- 
tent from the intermediary cells. Here all meet in 
close relation with the terminal branches of the pyr- 
amidal, and in the rabbit the bicornuate cells, and 
the nerve-impressions are carried through the 
medium of the bulbous tip of the gemmule and its 
stem to the protoplasm of the branch, and through 
this to the body of the cell. 
It may be readily seen that, according to this 
arrangement of the fibers, no matter how small the 
swelling of the dendron and loss of the gemmules 
may be, there is an instant disruption of the close 
connections between dendron and nerve end- 
apparatus, and consequently imperfect carriage 
of nerve-impulses from neuron to neuron; and 
should the destruction proceed to any consid- 
erable extent, and involve a moderate number 
of the protoplasmic extensions of the nerve-cells, 
that a serious disturbance of the mental and motor 
functions of the cortex will result, ending eventu- 19 
ally in partial or complete annulling of all the 
mental faculties of the animal. 
None of the bodies of the cells of Class B shows 
any noticeable alteration in structural arrangement, 
the destructive process having apparently to ad- 
vance to a greater degree than is found with the 
moderate degeneration of the dendrites. 
Class C, Cells Extensively Involved in the 
Degeneration. 
This class is almost entirely absent from the cor- 
tex of Brain No. 2, but in the other cerebra it con- 
stitutes a moderate proportion of the diseased cells, 
especially in Brain No. 3. The dendrons are now 
shortened to mere stumps ; the finer branches have 
entirely disappeared ; the coarser ones are irregular 
in outline and have large and small swellings upon 
them, and are much thinned, very often terminat- 
ing in an enlargement at a short distance from the 
cell-body, having a thin, pointed projection extend- 
ing out of it in the direction of the line of the former 
process. The gemmules have now entirely disap- 
peared, not a single one being visible on the por- 
tions of the dendrites that remain. The cell-body 
presents under these conditions two entirely differ- 
ent appearances, even when the dendrites are 
disintegrated equally. In the first one the ecll- 
body, where the processes have almost disap- 
peared, retains its smooth and rounded form ; sel- 
dom, indeed, is it roughened, and to all appearances 
the condition is one of health. In the other class 
the protoplasmic extensions have the same general 
aspect, but now the corpus is distinctly involved in 20 
Flo. 3. 
Fig. 4. 
Flo. 5- 
Fig. 3.—A cell from the same region, showing atrophy and de- 
struction of all the dendrons. The gemmules are only present at 
one point on the ascending process, and the cell-body is consid- 
erably eroded. 
Fig. 4.—Small pyramidal cell, showing complete loss of the 
protoplasmic branches and gemmules, with roughening and 
shrinkage of the cell-body. 
Fig. S-—A long pyramidal cell from the lowermost portion of 
the second cellular layer, showing the swellings and shortening of 
the ascending process, loss of the gemmules, and great erosion of 
the cell-body. 
Zeiss, ocular 4, objective E. 21 
the destructive metamorphosis. The edges of the 
cell are roughened and irregularly eroded ; deep 
excavations proceed from the periphery toward the 
central regions of the body; and, in exceptional 
and very advanced instances, nothing but a mass of 
detritus, blackened by the silver-salt, is seen occu- 
pying the site of the cell-body. In the last event 
nothing but the barest traces of the prolongations 
of the cell are to be found. 
Fig. 6. 
Micro-photograph of a stout ascending process of a large 
normal pyramidal cell, showing the arrangement of the lateral 
buds. A number of finer dendrons are included in the photo- 
graph. The fine granular lines indicate dendrons and vessels 
that were not fully in the focus of the camera. 
The nerve-fibers of the layers are quite freely 
stained in many of our sections, but even when the 
degeneration of the dendrons or of the cell-body is 
particularly well marked there is no lesion of this 
portion of the neuron. Cells that are greatly frayed 22 
Fig. 7. 
Fig. 8. 
Fig. 7.—Micro-photograph of the finer portion of the ascend- 
ing process of a normal long-stemmed pyramidal cell, showing 
the arrangement of the gemmules. 
Fig. 8.—Ascending process of a pyramidal cell from a serum- 
brain from the same level as Fig. 7. The tumefactions and loss 
of the gemmules are very distinctly shown. 
Flo. 9. 
Bifurcation of the long process of a pyramidal cell from a 
serum-brain, showing a swelling of the normal enlargement at the 
forking, loss of the gemmules over it, and large knots in the course 
of the finer branches. Enlargement about 550 diameters. 
and eroded in their bodies have perfect neuraxons, 
and these may be traced far downward into the 23 
white medullary layers. Cells that are apparently 
almost totally destroyed are too few in number to 
allow of any accurate knowledge of their axon. 
The collaterals of the axis-cylinders of the pyramidal 
cells may be followed to their bulbous free extremi- 
ties ; nor do fibers coming from more distant regions 
and passing upward, to terminate in the molecular 
lamina, show anything but a perfectly natural con- 
dition. There is no increase of varicosity, no breaks 
in the staining of the nerve-thread, no difference in 
the appearance of the terminal apparatus. 
Cortex of the Cerebellum. 
The changes in the nerve-bodies resemble those 
in the cerebrum, but are less intense. The twigs of 
the Purkinje cells are often bared of their protoplas- 
mic fur, have an occasional swelling, but are not 
highly degenerated. Normal Purkinje cells pre- 
ponderate over abnormal ones. The free extremities 
of the dendrons show the alterations to a greater 
extent than the ones closer to the corpus of the cell, 
as if the swelling were just beginning. The neur- 
axons of these bodies are distinct and perfect. The 
Korbzellen stain infrequently, and nothing definite 
can be said of them. The Golgi cells are well 
shown, but alterations in them are slight. 
Very numerous axons from the Korbzellen, Golgi 
and recurrent branches of the Purkinje cells are well 
stained in the molecular layer, but show nothing 
abnormal. Some beautiful specimens of the arbo- 
rescent endings of the fibers intermingling and ter- 
minating among the branches of the Purkinje cells 
were found, but they also were perfectly normal, 24 
to all indications. The neurogliar structures, 
both in cerebrum and cerebellum, stained in num- 
bers neither above nor below the control, and show 
no structural changes in their protoplasm deviating 
from the normal preparations. The degeneration 
of the nerve-cells is, therefore, probably a simple 
non-inflammatory process, unaccompanied by any 
proliferation of the supporting elements. 
While the small number of the pathologic serum- 
brains does not allow us to speak with entire posi- 
tiveness of the lesions of the cortical cells, yet from 
their constancy in all our preparations it is more 
than probable that we have found a new class of 
degenerative changes of the nerve cell that will 
ultimately prove of the greatest importance in a 
long series of irritative abnormal conditions in the 
human subject, and will also open up a new field 
for the student of mental changes. 
The absence of vascular lesions of importance 
precludes the possibility that alterations of nutrition 
from disease of the vessels are of the first importance 
in the production of the degeneration of the den- 
dron. Much rather would we refer them to the 
direct action of the toxalbumin upon the cellular 
protoplasm, causing, in some unknown manner, at 
first swelling of the substance of the dendron, and 
later atrophy and destruction. The Medical News. 
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