THE VASCULAR CHANGES OF 
TUBERCULOUS MENINGITIS, ESPECIALLY 
THE TUBERCULOUS ENDARTERITIS 
BY 
LUDVIG HEKTOEN 
From 
THE JOURNAL OF EXPERIMENTAL MEDICINE 
Vol. I, No. i, 1896 THE VASCULAR CHANGES OF 
TUBERCULOUS MENINGITIS, ESPECIALLY THE 
TUBERCULOUS ENDARTERITIS. 
By LUDVIG HEKTOEN, M. D., 
Chicago. 
(From Prof. Chian's Pathological Institute in Prague.) 
plate VIII. 
The pathogenesis of tuberculous meningitis presents many ques- 
tions of interest. 
The favourite point of localization of the specific granulations of 
this frequent and intense process about the arteries, especially the 
Sylvian ; the manner of primary invasion of the bacilli and of their 
secondary diffusion ; the presence or absence of a mixed infection— 
these are some of the interesting problems that merit consideration. 
In this article it is proposed to study somewhat in detail the his- 
togenetic vascular changes in the leptomeninx in tuberculous inflam- 
mation, on account of their interest from the purely histological 
aspect and also of their possible significance as regards the mode of 
infection. 
First it will be advisable to consider in general the various 
routes by which the infection may take place in tuberculous menin- 
gitis. Then it will be in order to introduce the more important 
statements in the literature concerning the arterial changes in the 
disease in question and their relation to the mode of infection. 
Upon this basis will be developed the results obtained by the bac- 
teriological and histological examination of a number of instances of 
tuberculous meningitis, and also from certain, as yet unfinished, ani- 
mal experiments. 
The development of our knowledge concerning tuberculous 
meningitis is, naturally, very closely connected with that of tuber- 
culosis in general. 
Copyright, 1896, by D. Appleton and Company. 2 
The Vascular Changes of Tuberculous Meningitis 
The descriptions by Coindet * and Papavoine of the minute nod- 
ules characteristic of the tuberculous form of meningitis called at- 
tention forcibly to the question of the genesis of these peculiar ele- 
ments. In the course of years the opinion gradually formed that 
the miliary granulations stood in some relation to the caseous masses 
nearly always found somewhere in the body of those dead from 
“ water on the brain.” Often tuberculous meningitis was, so to 
speak, only a part of a general miliary tuberculosis which Buhl, 
in 1872, characterized as an infectious and resorption disease, the 
miliary nodules bearing the same relation to the caseous foci as the 
metastatic abscesses of pyaemia to the primary pus focus. 
Taking the accumulated facts into consideration, and especially 
the constant distribution of the tubercles along the pial vessels, the 
occasional limitation of the process to one definite arterial territory, 
together with the well-nigh constant presence of caseous masses 
somewhere in the body, Huguenin, writing in 1878, found the con- 
clusion warranted that tuberculous meningitis usually originated 
from embolism by way of the blood of an unknown agent contained 
in, and most likely the cause of, the older tubercular lesions. This 
conclusion received material support by his finding perforation of a 
softened caseous focus into a pulmonary vein in an instance of gen- 
eral miliary tuberculosis with tuberculous meningitis. 
Koch’s discovery of the tubercle bacillus, and Weigert’s con- 
clusive anatomical demonstration of the routes of entrance from 
local areas of tubercle, subsequently furnished the direct and positive 
proof of what was generally believed to be the case from the cir- 
cumstantial evidence mentioned. 
The consideration of the mode of entrance of the tubercle bacil- 
lus in the meninges and the relation of tuberculous meningitis to 
tubercle elsewhere have, as already indicated, received ranch atten- 
tion, and a large number of observations bearing on this point may 
be found in the clinical and statistical studies of Seitz, Henoch, 
Demme, Muller, Wortrnann, Eieder, Medin, Reinhold, Horthrup, 
* The references to the literature are arranged at the end of the article and in alpha- 
betical order, according to the names of the authors. Ludvig Hektoen 
3 
Klotsch, Neumann, Simon, and others. Suffice it to say that it is 
the general belief that in nearly all instances of tuberculous menin- 
gitis the invasion occurs by way of the blood, which may become 
infected, as shown by Weigert and others, from local tuberculosis, 
either directly from extension to the walls of veins or of large ar- 
teries, or indirectly through the lymph stream. 
Often tuberculous meningitis is a terminal event in cases of ex- 
tensive infection with the formation of multiple, chronic, and case- 
ous foci and the diffuse eruption of miliary granulations in various 
organs, so that while it is perhaps no longer possible to trace any 
exact sequence of events, yet there can be no doubt of the originally 
hsematogenous nature of the general infection. But many cases also 
occur in which the meningeal infection develops in connection with 
local circumscribed, often latent, foci in the lymph glands, the lungs, 
the pleura, the bones and joints, the skin, etc., and in these instances 
the blood is also held as the carrier of the bacilli, although a few 
authors attribute this role to the lymphatics in certain special cases. 
Babes thinks that when the peribronchial or retropharyngeal glands 
are especially involved, then the bacilli may reach the brain by 
retrograde transport in and along the lymphatics.* Hiibbenet 
assumes the same route in one case of tuberculous meningitis occur- 
ring in connection with primary tuberculosis of the peribronchial 
lymph glands. Demme has an example of a probable lymphogenic 
pial infection from tuberculous rhinitis.f 
Acute tuberculous meningitis following old foci in the brain, the 
spinal cord, and the skull or spinal column, is, of course, most likely 
due to a direct infection of the lymph spaces of the internal me- 
ninges. The inflammation, commencing in the vicinity of the point 
of origin, may become diffuse by dissemination of the bacilli through 
the cerebro-spinal lymph vessels (Ziegler) ; in addition a local dis- 
semination through the arteries might also occur. 
Concerning the occasional instances of so-called spontaneous ” 
* The plexus jugularis profundus runs along the deeper vessels in the neck to the base 
of the brain, where it receives lymph from the cranial cavity.—Gegenbaur. 
f The subarachnoid space communicates with the mucous membrane of the nose.—Stohr. 4 
The Vascular Changes of Tuberculous Meningitis 
or “ primary ” tuberculous meningitis, it can confidently be said 
tliat but very rarely, if at all, has the anatomical investigation been 
thorough enough to exclude all the primary hidden foci tliat may 
have been present as the origin of a hsematogenous invasion. And 
yet the possibility of a primary meningeal tuberculosis (without 
the presence of an old focus) can not be denied. The demonstra- 
tion by Straus of virulent tubercle bacilli in the nose of nine 
seemingly healthy persons out of twenty-seven examined, cer- 
tainly warrants the suggestion that in some way tubercle bacilli 
might, under exceptional circumstances, such as after trauma 
(Demme, Coats*), be imported into the subarachnoid space, and 
thus cause a leptomeningitis in the same manner as appears 
to be the origin of many cases of non-metastatic cerebro-spinal 
meningitis. 
Perhaps tubercle bacilli might also enter the pia from the middle 
ear, in which Kossel found them in a nursling. 
Under all circumstances, the hsematogenous origin of tuberculous 
meningitis (which is not the result of direct infection of the lymph 
vessels from chronic foci in the nervous system) must be regarded as 
the general rule, and all other possible modes of infection as excep- 
tions of uncommon occurrence. 
In accordance with the etiological considerations referred to in 
the preceding pages, the distribution of the tubercles along and upon 
the vessels in tuberculous meningitis is usually spoken of as a mat- 
ter of course, as the direct result of the import of the bacilli by the 
blood; but, as may be seen from the usual descriptions of the mor- 
bid anatomy of this process, it can not be said that the exact rela- 
tions of the vascular changes to the primary localization of the bacilli 
is very clearly understood. Indeed, it will very soon become clear 
that, notwithstanding significant isolated observations and also im- 
portant special studies, such as those from Eindfleisch, Cornil, 
Guarnieri, and others, yet the changes in the arteries, as well as in 
* Coats, in an instance of tuberculous meningitis developing after trauma, found tuber- 
cles in an organized dural clot. There were no tubercles in any other part of the body. 
The route of the infection is not discussed. Ludvig Hektoen 
5 
the veins, in tuberculous meningitis have in reality not been system- 
atically studied in all their bearings. 
It is well to begin the review of the literature concerning the 
arterial changes in tuberculous meningitis with one or two citations 
about arterial tuberculosis in general. 
Orth states that until recently it was thought that the media and 
the intima were so immune from tuberculosis that they were never 
attacked either primarily or secondarily, but that newer investiga- 
tions show that the intima may proliferate and form giant cells as 
well as tubercles independently of adventitial changes. 
Ziegler teaches that tuberculous arteritis may come from infec- 
tion by the blood, and that in tuberculous organs the arterial walls 
may be invaded by bacilli, giving rise to tubercle or to more diffuse 
inflammation and proliferation resulting in thickening of the wTall 
that may end in caseation with thrombosis or rupture. 
Among the first to study closely the histology of the miliary 
tubercles in the pia was Rindfleisch, who found the larger arteries 
the seat of a unilateral swelling, while the smaller presented spindle- 
shaped thickenings, all of which he believed were due to changes 
that originated in the adventitia. 
Yirchow writes that, generally speaking, it is easy to convince 
oneself that not the vessels, but the ground substance forms the 
matrix for the tubercles in the adventitia of smaller pial ar- 
teries. 
Huguenin calls particular attention to his having observed that 
the miliary tubercles in tuberculous meningitis develop not only out- 
side the blood vessels, but also from the endothelial lining of their 
interior, and that tubercles may perforate the vessel wTall from within 
as well as from without. 
Danforth, in 1878, concludes that the lesions peculiar to tuber- 
culous meningitis are confined to the smaller blood vessels of the 
pia, and that they are always exterior to the tunica interna, and 
therefore have no structural relation to the circulating blood. 
Lancereaux says the miliary granulations take birth in the 
lymphatic sheath of the blood vessels, most frequently at the 6 
The Vascular Changes of Tuberculous Meningitis 
point of bifurcation, being produced by multiplication of the 
nuclei and the cells which enter into the composition of the 
adventitia. 
Baumgarten agrees with Brodowski, Cornil, and Kiener that 
occasionally the endothelium may proliferate in tuberculosis of the 
arteries of the pia mater, but this is usually not extensive, and in 
fact an exception rather than a rule. 
Arnold observes that he has found tubercles in the intima of 
larger vessels, and cites the similar observations of Ponfick in regard 
to the thoracic duct, of Weigert as to the pulmonary veins, and of 
Cornil in connection with the vessels of the pia, but concludes that 
it is impossible at the time of his writing to determine whether any 
of these vascular changes bear any relation to the spread of the 
tuberculous process or not. 
Guarnieri studied the histological changes in twelve cases of 
tuberculous meningitis. Besides adventitial changes, the exudate, 
infiltration into nerves, and a hyaline degeneration of the vessel 
walls, he also demonstrated quite constant changes in the media and 
in the intima. The intima presented semilunar or circular accumu- 
lations of round and epithelioid cells in a granular substance be- 
tween the endothelium and the elastic lamina so that the lumen was 
more or less narrowed. He found no giant cells in this proliferation, 
and but few tubercle bacilli compared to the number outside the 
arteries. This endarteritis, present also in the spinal pia and in the 
interior of the brain, was always accompanied with an older peri- 
arteritis and mesarteritis, the muscle fibres disappearing from the 
infiltration of round and epithelioid cells which frequently formed 
accumulations outside of the elastic layer. Guarnieri regards the 
changes as going from without inward. 
Cornil, in 1880, found not only the usual adventitial changes, 
but also special changes in the intima which he characterized as an 
endarteritic or endophlebitic tuberculosis. Between the endothelium 
and the media of the arteries was a series of layers of voluminous 
cells, flattened by mutual compression, and among them cells with 
two to four nuclei as wrell as veritable giant cells with fifteen to Ludvig Hektoen 
twenty nuclei. There was no marked production of limited nodules, 
but rather a uniform proliferation. 
Cornil and Banvier reproduce this description with the appro- 
priate drawings in their Manuel d?llistologie of 1881. 
Cornil and Babes describe, in addition to the tuberculous end- 
arteritis of Cornil, the presence of tubercle bacilli in the endarteritic 
granulations, in the thickened and caseous walls, and in the interior 
of thrombosed arteries and veins, and they give several figures illus- 
trating these observations. 
While Cornil and Babes lay much stress on the active part taken 
by the vessels in the histological changes, yet they do not emphasize 
the relation of such changes to the route by which the bacillus enters 
the leptomeninx. In another communication they express the opin- 
ion that the spread of the bacilli through the blood is proved by 
finding them in or near the vessels. 
Huettenbrenner, in examining the brain of a boy who died from 
basilar meningitis, found, among other changes, a typical tubercle 
with giant cells and caseation in the intima of a basal artery. The 
tubercle was located between the endothelium and the media, there 
was no oblique perforation of the vessel, and Huettenbrenner re- 
gards this as a primary intimal tuberculosis from direct implanta- 
tion of the bacilli. 
Bindfleisch teaches (in the last edition of his text-book) that the 
secondary localization of the tubercle bacillus which leads to a dis- 
seminated or general miliary tuberculosis occurs upon the smaller 
vessels, and that the classical place for studying the resulting tuber- 
culous vasculitis is the basal arterial system of the brain, especially 
the sheath of the Sylvian arteries, whose adventitia will show the 
miliary granulations. In these cases the internal coats become sec- 
ondarily involved and infiltrated with tubercular proliferation. On 
cutting open such a vessel longitudinally, one finds, in place of the 
familiar folds in the intima and the transverse striation of the mus- 
cular fibres, a sharply circumscribed defect occupied by tuberculous 
granulation tissue. 
Bindfleisch has repeatedly found places in which it appeared to 8 
The Vascular Changes of Tuberculous Meningitis 
him as though the epithelioid cells originated from the muscular 
fibres and not from emigrated leucocytes, and he has a figure entitled 
u Muscular fibres which appear to be changing into tubercle cells.” 
In other words, Kindfleisch regards the secondary localization of the 
bacilli as occurring in the adventitia of the vessels. 
Birch-Hirschfeld states that the bacilli are assumed to reach the 
pia through embolism, and then to spread diffusely through the 
lymph spaces. The vessels certainly partake in the inflammation, 
but the changes consist rather in a diffuse cell infiltration than in 
the formation of tuberculous nodules. 
Hirschberg studied three cases of tuberculous meningitis which 
presented focal symptoms before the appearance of the usual clinical 
manifestations. In two of these cases there was an endarteritis as 
well as an endophlebitis, with tubercle bacilli, giant cells, and casea- 
tion. The vascular process, older than that near by, is consequently 
regarded as the immediate source of the pial infection, the blood 
carrying the bacilli from the endarteritic focus. Hirschberg did not 
find any point at which the process had broken through the endo- 
thelial lining which covered the intimal proliferation ; nevertheless, 
this must have occurred, because in one case the peripheral, smaller 
arteries, though quite normal, were filled with granulation cells 
instead of with blood. 
The source of the endarteritic infection is not discussed, but it is 
evident that the bacilli did not penetrate the arterial wall from with- 
out inward, but must have come with the blood.* 
Ziegler observes that tuberculous meningitis is usually metastatic, 
but it may originate from adjacent structures. The tubercles may 
* Of a somewhat different origin is the endarteritis described by Weintraud in the case 
of a man with pulmonary and laryngeal phthisis, who was taken with sudden nervous symp- 
toms pointing to a local brain disease, but after eight days a fatal tuberculous meningitis 
supervened. 
Microscopically, the intima of the arteries in the older tuberculous meningeal foci was 
concentrically thickened on account of the accumulation of spindle- and star-shaped cells 
lying in a homogeneous and fibrillary ground substance. There were occasional giant cells 
with traces of degeneration, but no tubercle bacilli, no tubercles, and no distinct caseation 
in the intima. 
Weintraud declines to consider the disease of the intima as the primary process from 
which the meningeal infection followed, but he regards the endarteritis as secondary to a Ludvig Hektoen 
9 
develop anywhere in the pia, hut the vessel walls are often involved 
to a marked degree, so that the structure is no longer recognisable 
on account of the caseation and the thrombosis. 
Hamilton writes that the tubercles lie in the trabeculae of fibrous 
tissue between the pia and the arachnoid, and that a small artery is 
generally found embedded in their substance or lying at their side. 
The actual facts, gathered from this review of the literature con- 
cerning the arterial changes in tuberculous meningitis and their re- 
lation to the commencement of the process, may be summarized as 
follows: 
The general opinion seems to be that the bacilli, carried by the 
blood, are localized in the arterial adventitia. The resulting process 
may invade the media and the intiraa, and the whole or a part of the 
wall may become caseous (Bindfleisch, Ziegler, Birch-Hirschfeld, 
Lancereaux, Guarnieri). 
An endarteritis is also described whose relation to the other 
changes may vary. Some regard it as secondary (Guarnieri and 
Baumgarten), either due to direct extension or induced indirectly 
and somewhat in the same manner as chronic perivascular processes, 
tubercular or otherwise, call forth an obliterating endarteritis, a 
typical example of which Weinfraud describes in a tuberculous pia. 
Others regard the endarteritis as primary (Huguenin, Huetten- 
brenner, Cornil, Ilirschberg), as due to the direct implantation of 
tubercle bacilli from the blood (Cornil, Huettenbrenner), and as 
the immediate source of the general infection of the pia (Hirsch- 
berg). 
Concerning the histological technic used in this study, it is neces- 
sary to sa}7 simply this: That the paraffin-embedded pieces were cut 
into perfect series of sections from 5 to 10 fx in thickness, and that 
latent meningitis in circumscribed cortical districts and as identical in its nature with the 
endarteritis obliterans of Friedlander, which may result from chronic inflammatory changes 
in the neighbourhood of vessels. Weintraud cites Rindfieiseh, Friedlander, Baumgarten, 
Cornil and Guarnieri as having observed this or a similar form of endarteritis accompany- 
ing‘tuberculosis in the pia as well as elsewhere. 
According to Guarnieri, Marchiafava, in 1876, directed attention to an angeiitis oblit- 
erans in chronic tuberculosis of the lungs, the brain, and the testicles. 10 
The Vascular Changes of Tuberculous Meningitis 
the ordinary staining procedures were employed after affixing the 
sections to the slide with the water-albumin method. 
In all cases the examination was directed especially to the arteries, 
particularly those in the Sylvian fissures. 
The serial-section method presents obvious advantages that are 
indispensable in a study of this kind. Without perfect series of sec- 
tions the relations of the arterial and the venous changes and of the 
extravascular and the intravascular changes to each other could not 
be clearly and perfectly understood in all the details. 
Case I.—From Prof. Ganghofner’s Paediatric Clinic : Boy, five 
years old. 
Clinical Diagnosis.—Basilar meningitis (miliary tuberculosis ?); 
diffuse bronchitis; tuberculosis of the left elbow joint and of the 
cervical lymphatic glands. Section twenty-four hours after death 
(April 11, 1895). 
Anatomical Diagnosis.—Basal and spinal tuberculous meningitis ; 
chronic tuberculosis of the right lung, of the peribronchial lymph 
glands, of the cerebellum, of the right zygoma, of the left elbow 
oint, of the cervical and mesenteric lymphatic glands ; bilateral 
fibrinous pneumonia ; decubitus. 
The body is 103 centimetres long-, very emaciated. In the sacral region 
a 4-centimetre-large bedsore; about the left elbow joint are several fistulous 
openings that lead to rough bone. Over the right zygomatic arch opens a 
sinus that also leads to dead bone. The neck is thin, the thorax flat, and 
the abdomen retracted. 
The skull is 51 centimetres in horizontal circumference, the inner sur- 
face being slightly roughened and the sutures somewhat loose. The dura 
is tense. The pia over the base contains a light turbid fluid, and around 
the vessels of the Sylvian fissures are numerous gray miliary granulations; 
here the exudate is more gelatiniform. The same changes are found about 
the arteries of the corpus callosum. On the upper surface of the cerebellum 
the meshes also contain miliary and submiliary nodules. The convolutions 
are flattened, and all the ventricles are dilated with turbid serum. The 
ependyma of the lateral ventricles is almost confluent. The brain sub- 
stance is soft and moist. Along the anterior margin of the left cerebellar 
hemisphere is a caseous nodule, one cubic centimetre in size, which substi- 
tutes part of the cerebellar cortex, and is connected with the pachymeninx. 
The nasal cavities are normal; the lining is covered with yellowish 
mucus. The thymus and thyreoid glands are of usual size. Many of the Ludvig Hektoen 
11 
cervical lymph glands are caseous. The right lung is universally adherent; 
the left is free. In the pleural adhesions over the right lung are numerous 
small caseous masses. The right lung is pale; in the lower part of the 
upper lobe is a cavity 2 centimetres in diameter, with caseous and fibrous 
walls; in the vicinity are caseous nodules. In both the lower lobes the 
parenchyma is hepatized without caseation. The heart is of normal size, 
the valves thin. The peribronchial glands are in part caseous. 
The abdominal organs show no pathological changes, but the mesen- 
teric glands are in part caseous. 
The spinal pia is infiltrated with turbid serum, especially in the dorsal 
part, and contains many miliary nodules. The spinal cord is normal. 
Bacteriological Examination.—Several cover-glass preparations 
of the meningeal exudate show no tubercle bacilli or other micro- 
organisms, and a gljcerin-sugar-agar plate from the same exudate 
remained sterile after fifteen days in the incubator. Cover-glass 
preparations from the nose contain a large mixture of various 
bacteria, and among the numerous colonies on the plate cultures 
from the nasal muco-pus a staphylococcus staining with Gram’s 
method seems the most prominent. In addition, cover glasses 
from the superior meatus on the left side contain a few tubercle 
bacilli. 
Cover glasses from the pneumonic districts in the lungs show 
diplococci that take the Gram stain in rather small numbers. 
Histological Examination.—The internal meninges present the 
usual changes, consisting of diffuse as well as more circumscribed 
cell infiltration, with comparatively many giant cells and occa- 
sional districts of caseation, and also much fibrinous exudate (Wei- 
gert’s fibrin stain), all of which seems to be more marked at the base 
and in the beginning of the Sylvian fissures. 
The caseation and the giant cells seem most pronounced in and 
around the adventitia of the smaller arteries, and quite frequently 
the infiltration and the caseation involve the entire media, either 
at only one point, or around the whole circumference of the vessel 
for a short distance longitudinally. In such instances there is usu- 
ally more or less proliferation in the intima between the endothe- 
lium and the elastic lamina, but the latter usually remains intact. 
This invasion of the media with thickening of the intima is strongly 12 
The Vascular Changes of Tuberculous Meningitis 
marked at the periphery of the older focus in the cerebellum. The 
accumulation of cells between the endothelial lining, which is well 
preserved, and the elastic layer usually consists of large epithelioid 
cells, with but occasional small lymphocytes and multinuclear leuco- 
cytes. Distinct tubercles and giant cells wrere not found upon the 
intirna, and the changes in the external coats of the arteries usually 
seem older than those in the internal. Many of the smaller arteries 
are diffusely infiltrated and caseous, being, so to speak, directly 
transformed into tubercles. The main stem of the left Sylvian 
♦ 
artery presents, at a point where it is free from adventitial changes, 
a nodular accumulation of lymphocytes and cells with multiform 
nuclei upon an intact intima. 
The veins are frequently the seat of a marked infiltration wdiich 
always seems to proceed from an artery or from changes in the 
neighbouring tissue; it is not unusual to find giant cells in the ve- 
nous walls lying almost next to the blood stream. In one place a 
vein becomes the seat of two foci of circumscribed infiltration ap- 
parently by extension from a diffuse arteritis in two neighbouring 
arteries; the masses of granulation cells project into the lumen of 
the vein and become capped with thrombotic masses. 
The internal meninges of the spinal cord show considerable 
exudation and infiltration whicti extends out into the nerve roots. 
In the arteries only the adventitia is usually involved, but the veins 
are often the seat of a diffuse proliferation with many giant cells; 
in some places the vein wall becomes very considerably thickened, 
and the lumen much narrowed. The walls of the minute arteries 
may be diffusely infiltrated. In addition to the giant cells—which 
are present in very large numbers and are remarkable for their size, 
the number of the so-called nuclei often reaching above one hun- 
dred, and the arrangement of the latter in the granular mass of the 
cell body forming at times a high wTall at the periphery of the cell, 
at other times a heap in its centre or at one pole—three distinct 
kinds of cells are to be distinguished in the areas of proliferation : 
namely, small, round cells with comparatively large nuclei which 
stain deeply, and with a very small cell body (small lymphocytes) ; Ludvig Hektoen 
13 
and large cells of circular form, with relatively small nuclei and a 
finely granular, almost homogeneous cytoplasm (epithelioid cells— 
lymphatic cells, Metschnikoff); and, finally, cells with polymor- 
phous or fragmented nuclei found wherever caseation is going on. 
Tubercle Bacilli.—These are easily demonstrable in large num- 
bers in the old focus in the cerebellum and in the adventitial prolif- 
eration in both the brain and the cord. In sections from the cortex 
of the central convolutions bacilli are also present in small numbers 
in the interior and in the wall of small arteries with inflammatory 
changes. Bacilli were also found in the media and in the interior 
of small arteries with changed walls in the spinal pia. 
Case ll.—From Prof. Ganghofner’s Paediatric Clinic: Girl, 
seven and a half years old. 
Clinical Diagnosis.—Tuberculous meningitis. Section eighteen 
hours after death (April 20, 1895). 
Anatoviical Diagnosis.—Tuberculous meningitis ; chronic tuber- 
culosis of the peribronchial lymphatic glands, of the brain, the 
thyreoid gland, the lungs, the liver, the spleen, the kidneys, the 
stomach, and the intestines. 
The body is 103 centimetres long, of feeble build, and greatly emaciated. 
The rigor mortis is slight. The hair is brown, the pupils equal, the neck 
thin, the thorax fiat, and the abdomen retracted. 
The skull is 48 centimetres in horizontal circumference; the sutures are 
somewhat loose. The dura is tense; the dural sinuses contain fluid and 
clotted blood. The pial vessels are full of blood; at the base, especially 
about the optic chiasm, is much turbid, serous fluid; along the vessels of 
the pia, both at the base and over the surface, are numerous miliary tuber- 
cles lying in fibrinous exudate. The brain substance is moist and soft, 
especially near the ventricles, which are much dilated with turbid fluid. 
Here and there the cortex of both hemispheres of the brain contain case- 
ous nodules about the size of a pea, which are connected with the pia. The 
nasal mucous membrane is covered wfith thick yellow rnuco-pus. 
The thymus gland is of usual size. The thyreoid is rather large, and con- 
tains numerous areas of caseous infiltration. 
The laryngeal and tracheal mucous membrane is covered with yellow 
mucus. Both lungs contain numerous yellowish-white nodules, some as 
large as a pea. In the peribronchial lymph glands are caseous and cal- 
careous masses. The pericardium contains a tablespoonful of serum. The 
heart is of usual size, and its valves are thin. The liver contains numer- 
ous caseous nodules up to o‘s centimetre in diameter, with softened, bile- 14 
The Vascular Changes of Tuberculous Meningitis 
stained centres. The spleen is somewhat large, and contains caseous 
masses. The kidneys contain a few scattered miliary tubercles. The 
genital organs are normal. In the stomach are found occasional case- 
ous nodules as large as a split pea, some of which present ulceration 
on the mucous surface. In the inferior ileum and in the caecum are 
caseous nodules and also small ulcers. The pancreas and the adrenals 
are normal. 
Bacteriological Examination.—The cover glasses from the me- 
ningeal exudate contain a few staphylococci and occasional tubercle 
bacilli. 
Plate cultures show, after thirty-six hours, three pinhead-sized, 
grayish, round colonies of staphylococci that stain with Gram’s 
method, present a thick, grayish-white growth on slanting agar, 
liquefy gelatin, and make bouillon turbid. 
The cover glasses from the nose contain a mixture of various 
bacteria, staphylococci being present in large numbers. Tubercle 
bacilli are not found. 
Plate cultures from the upper as well as from the lower meatus 
contain mostly staphylococci identical with that from the me- 
ningeal exudate. 
Histological Examination.—ln this case the changes are very 
intense, as marked by the dense cell infiltration and by the exten- 
sive degeneration. Giant cells are frequently present, especially in 
the peri-arterial and para-arterial foci and in the wmlls of veins. 
The inflammation in places involves the superficial layers of the 
brain cortex and extends also inward in the perivascular tissue of 
the intracerebral vessels. In many places the peri-arterial infiltra- 
tion and caseation is accompanied by a hyaline degeneration of the 
media, whose inner layers, especially, then present a homogeneous, 
structureless appearance, the intima usually showing some subendo- 
thelial proliferation. The wall of the left Sylvian artery presents at 
one point a circumscribed infiltration, most marked in the adventitia 
and the outer layers of the media, but reaching the intima. Farther 
out in the Sylvian fissure there is quite a marked subendothelial pro- 
liferation in the large arteries with but slight if any changes in the 
media or the adventitia ; the elastic layer remains intact, and there Ludvig Hektoen 
15 
are uo tubercles or giant cells upon the intirna. The arteries occa- 
sionally contain thrombi, in which may be accumulations consisting 
essentially of multinuclear leucocytes. 
The smaller arteries are often diffusely involved and changed 
into small tubercles. Circumscribed and diffuse infiltration into the 
walls of large as well as small veins, with frequent giant cells, is 
everywhere seen (Plate YIII, Fig. 6). From the serial sections it is 
easy to trace the affection of the veins to invasion from the neigh- 
bourhood. 
Tubercle bacilli are present in very large masses in the peri-ar- 
terial tuberculous infiltration ; they are also found in smaller num- 
bers in the walls of the smaller arteries. 
Case lll.—From Prof. Ganghofner’s Paediatric Clinic : Girl, four 
and a half years old. 
Clinical Diagnosis.—Tuberculous meningitis. Section fourteen 
hours after death (April 21, 1895). 
Anatomical Diagnosis.—Basilar and spinal tuberculous meningi- 
tis; chronic tuberculosis of the peribronchial lymph glands, of the 
brain, and of the fourth and fifth lumbar vertebrae; miliary tuber- 
culosis of the lungs, the liver, and the spleen; lobar pneumonia; 
multiple cartilaginous exostoses. 
The body is 93 centimetres long, of feeble build, and much emaciated. 
The rigor mortis is slight. The hair is light, the neck thin, the thorax 
long, and the abdomen retracted. There are a large number of cartilagi- 
nous exostoses in the vicinity of the lines of ossification in nearly all parts 
of the body. 
The skull measures 47‘5 centimetres in its greatest horizontal circumfer- 
ence. It is thin, the inner surface is a little rough, and the frontal suture 
is persistent. The dura is somewhat tense. The pia is hypersemic, and its 
meshes contain much thick exudate, especially at the base and in the begin- 
ning of the Sylvian fissures. Along the vessels, as well as elsewhere, are 
numerous miliary and submiliary nodules. The ventricles are dilated and 
filled with turbid serum. The brain substance is swollen and moist, the 
convolutions being greatly flattened. In the left cuneus and in the centre 
of the left first temporal convolution are caseous nodules, each the size of a 
pea. In both the cerebellar hemispheres are found several nodules up to o's 
centimetre in diameter. In the pons above the left locus cseruleus is also 
a small nodule; in the same section there is a caseous mass o‘s centimetre 
large in the ventral portion of the right half of the pons. 16 
The Vascular Changes of Tuberculous Meningitis 
The mucous membrane of the nose, the pharynx, and the larynx is pale. 
The thyreoid and thymus glands are of usual size. The lungs are hyper- 
semic and oedematous, and contain numerous miliary tubercles. The left 
lower lobe is hepatized. In the bronchi is considerable muco-pus. The 
peribronchial lymph glands are caseous. The heart is of usual size, the 
valves thin. The liver and the spleen contain miliary tubercles. The 
stomach, the intestines, and the genito-urinary organs are normal. In 
the left psoas muscle is a large abscess which occupies the entire extent of 
the muscle; in the fourth and fifth lumbar vertebrae are found areas of 
caries. The spinal pia is hyperaernic, infiltrated with serum, and here and 
there are miliary tubercles. 
Bacteriological Examination.—Cover glasses from the meningeal 
exudate contain isolated tubercle bacilli. Plate cultures from the 
meningeal fluid remain sterile. 
Tubercle bacilli are not found in the mucus from the nose. 
Histological Examination.—ln the Sylvian fissures the changes 
are very intense, the vessels being embedded in the diffuse infiltra- 
tion and the dense fibrinous exudate. The media of the larger 
arteries is usually diffusely infiltrated, the lumen frequently throm- 
botic, and along the tunica elastica is a layer of various kinds of cells 
with detritus and nnclear fragments, the endothelium being absent. 
The perivascular infiltration is in process of degeneration, and this 
extends into the media and at times through the entire wall. 
In other places there is a well-marked peri-arteritis and mes- 
arteritis with more or less hyaline degeneration in the media and 
with accumulations of leucocytes upon an intact endothelium. 
The veins show, as usual, extensive tubercular infiltration into 
the walls; in one place a polypoid mass of granulation cells projects 
from the wall into the lumen; in another place the sections of a 
large vein present a circumscribed infiltration into the wall, which 
appears to be undergoing disintegration, so that the internal surface 
presents an appearance that might be referred to as a tuberculous 
ulcer. Giant cells are frequent in the walls of veins, rare in 
arteries. 
Tubercle bacilli are found in large numbers in the more recent 
areas of proliferation. The character of the tissue is no sure indica- 
tion as to the presence of tubercle bacilli, which are easily demon- Ludvig Hektoen 
17 
strable in large numbers in one place and difficult to find or ab- 
sent in another, the histological appearances being the same in 
both. 
In a small artery in the Sylvian fissure, which presents a cir- 
cumscribed proliferation at one point, tubercle bacilli are found in 
the lumen of the vessel next to the intima. Tubercle bacilli are 
also present in the wall, and free in the lumen, of a small infil- 
trated vein of the pia over the central convolutions of the left 
side. 
Case IY.—From Prof. Ganghofner’s Paediatric Clinic: Girl, ten 
months old. 
Clinical Diagnosis.—Tuberculous meningitis. Section eighteen 
hours after death (April 24, 1895). 
Anatomical Diagnosis.—Basilar and spinal tuberculous menin- 
gitis; chronic tuberculosis of the peribronchial glands, the pericar- 
dium, the liver, the leptomeninx, the brain, and the cranium. 
The body is 70 centimetres long, well nourished, with livid discolora- 
tions posteriorly. Rigor mortis present. The hair is blond, the pupils 
equal, the neck short, the thorax oval, and the abdomen slightly distended. 
The skull measures 42 centimetres in horizontal circumference ; it is of 
usual thickness; the sutures are loose; the large foutanelle is 4 centimetres 
large. In the right inferior quadrant of the left temporal bone is an area, 
2 centimetres square, in which the bone is infiltrated with caseous material 
which invades the periosteum and the pachymeninx. In the sinuses of the 
dura is fluid blood. The pia does not contain much blood; at the begin- 
ning of the Sylvian arteries and the arteries of the corpus callosum are 
several pea-sized nodules in the pia which extend into the cortex; in addi- 
tion there is much serous and gelatiniform exudate, and also numerous 
miliary nodules along the vessels of the Sylvian fissures as well as else- 
where. The brain substance is pale, quite soft, especially around the dilated 
ventricles, where it is almost confluent. The fourth ventricle is also some- 
what dilated. The lining of the nose is covered with thick mucus. 
The trachea contains fluid from the stomach. The thymus and the 
thyreoid are of normal size. The 7ungs are not adherent; slightly oedema 
tons. The epicardium is thickened, and contains single and conglomerate 
caseous nodules as large as grains of wheat; at the upper part of the peri- 
cardium are adhesions between its two layers. The heart is of usual size, 
the valves thin, the muscle pale. The peribronchial lymph glands are 
enlarged and in part caseous. 
The liver contains caseous nodules, as large as a pea, with softened 
■centres. The spleen is of usual size. The kidneys are pale, the bladder The Yascular Changes of Tuberculous Meningitis 
18 
and genitalia normal. The mucous membrane of the stomach is softened 
in the pyloric region. The intestines are normal. The mesenteric glands 
are enlarged but not caseous. The spinal pia contains numerous small 
tubercles. 
Bacteriological Examination.—Cover-glass preparations from the 
meningeal exudate do not contain tubercle bacilli or other bacteria, 
and plates with the same material remain sterile at the end of three 
weeks in the thermostat. No tubercle bacilli were found in the nose. 
Histological Examination.—The larger arteries at the base, such 
as the Sylvian and the arteries of the corpus callosum, show the 
most intense involvement of the entire wall in infiltration and casea- 
tion, so that the structure of the arteries is no longer recognizable. 
The elastic layer seems to remain distinct the longest. This exten- 
sive affection of the wall is accompanied with similar violent changes 
in the neighbourhood. Upon the internal surface of the arteries 
occur frequent nodular accumulations of cells and detritus, covered 
with fibrin, but the degeneration is so advanced that one can not 
distinguish between possible miliary tubercles and parietal leucocytic 
masses. 
At a point where the tuberculous process is not so intense the 
left Sylvian artery proper presents a small, sharply circumscribed 
perforation filled with granulation tissue, and the changes in the 
intima are certainly as old at this point as those in the adventitia. 
The walls of the adjacent smaller vessels usually show a total hyaline 
degeneration with thrombosis. 
In the Sylvian fissures the changes are also very marked ; the 
infiltration into the adventitia and the media is usually accompanied 
with endarteritis, the media remaining at times nearly normal, at 
times becoming homogeneous and hyaline. The subendothelial pro- 
liferation usually appears most marked at the points of bifurcation 
of the arteries. 
In some places the entire segment of an artery may be totally 
necrotic. The veins present infiltration and caseation in the same 
high degree as the arteries. The meningeal process frequently in- 
volves the subjacent cortex. Ludvig Hektoen 
19 
The old foci in the pia and the subjacent cortex are marked by 
the presence of a very large number of large giant cells and by 
severe vascular changes. 
In many places the spinal leptorneninx shows a sparse infiltra- 
tion, especially of epithelioid cells, into the lymph spaces, the walls 
of the veins, and the arterial adventitia. The number of large giant 
cells is considerable; they sometimes lie in the venous wall next to 
the lumen. The giant cells here present an appearance as though 
they were formed by the arrangement of nuclei in a homogeneous 
or finely granular mass that sends prolongations in all directions out 
among the adjacent cells. 
Tubercle bacilli are present in large masses in the wall of the 
Sylvian artery and in the arterial adventitia elsewhere. 
Case V.—From Prof. Ganghofner’s Paediatric Clinic: Girl, eight 
years old. 
Clinical Diagnosis.—Broncho-pneumonia ; miliary tuberculosis. 
Section nine hours after death (April 26, 1895). 
Anatomical Diagnosis.—Chronic tuberculosis of the peribronchial 
lymphatic glands of the right pleura and lung; universal subacute 
tuberculosis; tuberculous meningitis; subcutaneous emphysema. 
The body is 166 centimetres long, of slender build, and much emaciated. 
The hair is brown; the pupils equal. In the left supraclavicular fossa is 
subcutaneous emphysema that extends into the left axillary space; there is 
emphysema of less degree in the left supraclavicular fossa. The abdomen 
is somewhat retracted. 
The skull measures 47 centimetres in its horizontal circumference. The 
dura is tense; its sinuses contain fluid and clotted blood. The pia over the 
forebrain is hyperaamic and cedematous ; at the base, and especially along 
the arteries of the corpus callosum, are groups of mil let-seed-sized and larger 
caseous nodules ; here and there upon the convexities are occasional small 
yellowish masses around the vessels. The convolutions are flattened, the 
ventricles dilated with lightly turbid serum, the ependyma softened. The 
thyreoid contains many miliary nodules. The thymus is small. 
The right lung is totally adherent to the chest wall, and in the adhesions 
are many miliai’y tubercles and caseous nodules ; in the lung parenchyma 
are similar masses. The left lung is free, the cut surface displaying miliary 
nodules. The pericardium is adherent to the right visceral pleura, and 
contains a tablespoonful of clear serum. The heart is of normal size, the 
valves thin. 20 
The Vascular Changes of Taherculous Meningitis 
The peribronchial glands are enlarged and in part caseous. In the 
liver, the spleen, and the kidneys are many miliary tubercles. The stom- 
ach, the intestines, and the genital organs are normal. 
Bacteriological and Histological Examination.—Cover-glass 
preparations from the meningeal exudate contain only tubercle 
bacilli, which are present in large numbers. The bacilli occur most 
frequently in the interior of large, roundish cells, at times singly, at 
times in groups of four, six, ten, or more. Occasionally a bacillus is 
found lying directly across or upon the nucleus of the cell, but 
usually the bacilli occupy the cell body. 
These large cells are very numerous. They usually have but one 
nucleus, but cells with two or more nuclear bodies occur. Many 
such cells containing bacilli are necrotic; frequently the nucleus is 
split up into irregular fragments or replaced by round masses of 
varying size—karyolysis; detritus masses of the shape of disinte- 
grated cells are seen, and among the remnants may lie tubercle 
bacilli. 
Free tubercle bacilli, singly, but oftener in heaps or groups, are 
also found. 
In addition to apparently well-preserved as well as disintegrating 
cells, the meningeal fluid contains chromatin masses of varying size 
and shape, and also leucocytes with polymorphous nuclei. 
Glycerin-sugar-agar plates made with the meningeal fluid re- 
main sterile. The nose could not be examined. 
Serial sections through the smaller caseous masses in the pia over 
the convexity present the following appearances; Through the de- 
generated centre run one or two arteries whose adventitia and media 
are infiltrated and caseous, sometimes homogeneous and hyaline, the 
intiraa being the seat of a slight subendothelial proliferation, the 
lumen frequently thrombotic. Sometimes small hyaline masses 
occur in the intiraa. The arteries are surrounded on all sides by 
caseous material in which lie scattered fragments of nuclei and poly- 
nuclear leucocytes. The walls of the adjacent veins are invariably 
infiltrated ; often the lumen is partially or wholly occluded by throm- 
botic masses whose interior present foci of leucocytic infiltration. Ludvig Ilektoen 
21 
The process also involves the upper layers of the subjacent cortex. 
Toward the periphery of such a mass or tubercle the adventitia is 
more loosely infiltrated with large and small cells, the media usually 
quite normal, but the intima usually showing some subendothelial 
proliferation. Giant cells were not found in these areas; Weigert’s 
fibrin stain demonstrates considerable fibrin in their peripheral parts. 
The neighbouring lymph spaces are loosely filled with epithelioid 
cells, much like those found in the meningeal exudate, and contain 
free and intracellular tubercle bacilli in large numbers. 
Circumscribed, minute, tuberculous foci are also found in the in- 
terior of the brain without any demonstrable connection with the 
larger vessels. 
The arteries of the corpus callosum and their branches present 
the following appearances: The lumen is more or less occluded with 
thrombotic masses that often contain large accumulations of leuco- 
cytes. The endothelial lining is either absent or the cells lie loose 
and disarranged. Frequently the internal wall presents nodular 
masses of cells, which penetrate the elastic layer and invade the 
media in a semicircular manner, the whole presenting a tubercle one 
half of which extends into the lumen, the other half into the wall of 
the artery; the centre of such masses is usually caseous, but in one 
or two instances distinct giant cells are present. 
At one point the flattened artery is totally occluded by a large 
mass of cells and detritus in which lie several quite well-preserved, 
multinucleated giant cells; at the side of the mass that borders upon 
the main lumen of the artery lie several endothelial cells. 
Around this intravascular process the arterial wall presents 
diffuse inflammatory and degenerative changes which at times 
render the structure indistinct. Corresponding to such foci in 
the arteries are diffuse and extensive changes in the surrounding 
tissues which invade the cortex, but the only giant cells found are 
those in the intravascular tubercles. The walls of the smaller 
vessels that are embedded in such. masses are totally caseous or 
hyaline. 
From older foci the process seems to extend along in the ad- 22 
The Vascular Changes of Tuberculous Meningitis 
ventitia of the arteries, and at times a circumscribed invasion of the 
media may occur. 
The sections removed from the series of these large arteries for 
the purpose of demonstrating the tubercle bacilli did not happen to 
include any extensive intravascular changes. Bacilli are present in 
enormous numbers in the wall of as well as outside the arteries. 
Frequently dense heaps or masses of bacilli are found that are recog- 
nisable as violet spots (Ehrlich’s method) with a low power. 
Case Yl.—From the Medical Clinic of Prof. Pribram ; Man, 
aged forty-one. 
Clinical Diagnosis.—Tuberculous meningitis; sero-fibrinons 
pleuritis ; pulmonary emphysema; apical infiltration in the lungs; 
arterio-sclerosis; chronic alcoholism. Section twenty-four hours 
after death (May 17, 1895). 
Anatomical Diagnosis.—Chronic tuberculosis of the lung apices ; 
right tuberculous pleuritis; chronic tuberculosis of peribronchial 
lymph glands; universal miliary tuberculosis; basilar tuberculous 
meningitis; fibrous orchitis. 
The body is 170 centimetres long, the bones are light, the muscles 
poorly developed, the panniculus adiposus slight. Diffuse posterior livid- 
ities. The hair is thick, brown ; the pupils equal; the neck of medium 
length; the thorax rather flat, the right half larger than the left. The ab- 
domen is prominent. The skull is thick, 56 centimetres in circumference. 
The dura is tense, the sinuses containing fluid blood. The vessels of the pia 
are filled with blood, the meshes are oedematous and infiltrated with clear 
serous exudate, and along and upon the vessels are numerous minute gray- 
ish-white nodules. The brain substance is moist, the ventricles somewhat 
distended with clear fluid. 
The mucous membrane of the organs of the neck is normal but pale. 
The thyreoid is apparently normal. The left lung is adherent; in its apex 
is an old scar. The right pleural cavity contains more than one litre of 
sero-fibrinous fluid, and both pleural layers are covered with fibrinous 
exudate and tubercles. The right lung is pale and compressed; in the 
apex is an old calcified cicatrix. In both hmgs the bronchi contain muco- 
pus, the parenchyma being the seat of miliary tubercles. The pericardium 
contains a tablespoonful of fluid. The heart muscle is flabby and easily 
torn ; the valves are thin ; the aorta is smooth. 
The oesophagus is normal. The peribronchial glands are large and case- 
ous. The liver, the spleen, the kidneys, the pancreas, and the adrenals con- 
tain numerous miliary nodules. The testicles are hard, both layers of the Ludvig Hektoen 
23 
tunica vaginalis are adherent, and the parenchyma, especially in the right 
testis, is replaced by hard, white, fibrous tissue. 
The stomach is dilated and contains many haemorrhagic erosions; the 
ileum and the colon are normal. 
Bacteriological Examination.—Cover-glass preparations from 
the meningeal exudate contain tubercle bacilli in small numbers. 
Other bacteria are not present. 
Plate cultures from the exudate remain sterile after three weeks 
in the thermostat. 
Serum and glycerin-agar tubes inoculated with a drop or two of 
the meningeal effusion develop slowly-growing cultures of tubercle 
bacilli. The nose could not be examined. 
Histological Examination.—The tissues from this case presented 
astonishingly slight post-mortem changes, and proved an excellent 
material for the study of the vascular changes which involve the 
internal coats of the arteries to a remarkable degree. 
More or less acute endarteritis is present in almost all the arter- 
ies, large as well as small. In the large arteries, such as the main 
stem of the Sylvian, the process is usually limited to one part or 
segment of the internal circumference of the vessel. In the me- 
dium-sized arteries the proliferation oftenest extends completely 
around the vessel, and the smaller arteries are frequently more or 
less completely occluded by the loosely arranged accumulation of 
cells in their interior. It is in the medium-sized arteries that the 
specific characters of the process are best studied. 
The circumstance that the endothelium is unusually well pre- 
served renders it easy to recognise that the proliferation is invari- 
ably subendothelial. It is only under the special circumstances to be 
mentioned that the endothelial lining is absent. When the cell 
proliferation completely fills the lumen of the vessel, then the endo- 
thelial lining will be found in the central part, at times disarranged 
and rolled together, at other times undisturbed. 
The endarteritic proliferation is made up of cell layers of vary- 
ing thickness. Large round or oval cells with comparatively rather 
small nuclei are the most numerous and predominating elements. 2he Vascular Changes of Tuberculous Meningitis 
24 
Smaller cells with large, deeply stained nuclei and cells with poly- 
morphous or fragmented nuclei are also occasionally present. In 
some places one meets with cells containing three or four nuclei, as 
well as with multinucleated giant cells, and this outside of the more 
typical tubercles to be described (Plate YIII, Figs. 1 and 2). 
Generally speaking, there is no very distinct intercellular sub- 
stance; in some places a fibrinous and granular exudate is present 
in small quantity, especially in the deeper layers of the more ad- 
vanced proliferation. 
A well-preserved endothelium composed of a single row of 
typical endothelial cells limits the inflammatory proliferation on one 
side and the elastic layer (or the media) limits it on the other. 
There are absolutely no signs in the endothelium or disturbances 
of its arrangement which would indicate any active changes on its 
part. The nuclei of the endothelial cells are not swollen and pre- 
sent no appearances indicative of karyokinesis. 
At times the elastic layer is invaded by cells, and an infiltration 
of variable degree takes place in the media and in the adventitia, 
but one can also examine large series of sections without finding any 
changes in the elastic tunic, the media, or the adventitia. Then 
again an unchanged media may intervene between the endarteritic 
and the familiar peri-arteritic infiltration. In the smaller arteries 
the elastic layer may be completely absent. Usually the arteries 
are not thrombotic. 
At frequent intervals the more uniform and diffuse proliferation 
that has been described is intensified, as it were, by the formation of 
more or less distinctly nodular cell masses in which may be found 
giant cells and caseation. It is over suck caseous intimal tubercles 
that the endothelium may be absent (Plate YIII, Fig. 4). The cells 
in such tubercles apply themselves firmly to the arterial wall and 
appear closely packed together. The multinucleated giant cells usu- 
ally occur in the centre of the little nodules ; round about are 
epithelioid and small cells, and, as caseation becomes marked, more 
polynuclear leucocytes appear. 
Close study of the beginning of this subendothelial, intimal pro- Ludvig Hektoen 
25 
liferation shows that at first one or two cells appear in the intima 
here and there. A little later minute nodular accumulations of epi- 
thelioid cells have formed which lift the endothelium away from the 
intima, so that the endothelial lining presents a series of longitu- 
dinal folds corresponding to the subendothelial cell masses. The cells 
in such places present many evidences of proliferation in the shape 
of cells in the act of division, cells with two nuclei, and cells with 
more or less indistinct but nevertheless unmistakable karyokinetic 
nuclear figures. 
Any other disarrangement of the endothelium in these places 
than the mechanical one described is usually not observed, and the 
elastic layer and the media are unchanged. 
The elastic lamina underneath the tubercles may be quite intact, 
more or less infiltrated with cells, exudate and detritus, or entirely 
and sharply perforated as if a hole had been punched in it. Some- 
times exudate may lift the ends of the perforated layer away from 
the media (Plate YIII, Fig. 4). 
Corresponding to the tubercles, the media and the adventitia may 
be quite normal, or they may show infiltration and caseation of all 
grades of intensity. 
Cell masses with as well as without giant cells or caseation may 
occur in the intima of arteries where there are no other changes, 
either intravascular or extravascular, but this is not common. 
The walls of veins, large and small, show diffuse and circum- 
scribed infiltration, but without giant cells. 
The extravascular changes proper in this case consist of mod- 
erately extensive diffuse, as well as more circumscribed, infiltra- 
tion, with but little caseation and no giant cells. These changes 
are usually better marked in the pia itself than in the arachnoidal 
layer. 
There were no foci found in the interior of the brain substance. 
Tubercle bacilli are found in very small numbers in the intimal 
tubercles; but in many sections through such masses, including the 
giant cell, the search for bacilli was entirely in vain. Many small, 
round, and rod-shaped intracellular granules were found that retained 26 
The Vascular Changes of Tuberculous Meningitis 
the stain like the bacilli. In one place bacilli were found in the 
elastic layer, but occasional bacilli were found in the diffuse intimal 
proliferation. 
Bacilli were also found in the infiltrated walls of veins, and, in 
larger numbers, in the peri-arterial infiltration. 
Case Yll.—From the Psychiatric Division of Dr. Zastera: 
Woman, aged twenty-six. 
Clinical Diagnosis.—Melancholia, intestinal and pulmonary 
tuberculosis. Section thirty-six hours after death (May 29, 1895). 
Anatomical Diagnosis.—Tuberculous cerebro-spinal meningitis ; 
chronic tuberculosis of the peribronchial lymph glands, of the lungs, 
the liver, the spleen, and the kidneys. Tuberculous pleuritis. 
The body is 167 centimetres long and quite emaciated. Rigor mortis is 
present. The hair is light; the pupils equal and wide; the visible mucous 
membranes pale; the neck is thin; the thorax long and flat. The dura is 
tense, and the sinuses contain liquid and clotted blood. The pial vessels 
are full of blood, and the meshes are distended with turbid serum, espe 
cially at the base about the beginning of the Sylvian fissures. Along the 
vessels, principally those in the Sylvian fissures, are many small gray nod- 
ules ; on close examination some nodules appear to be situated in the wTalls 
of the vessels. The brain substance is moist and soft; the convolutions are 
flattened; the ventricles are filled to dilatation with turbid serum, the 
ependyma being softened. 
The mucous membrane of the nose and of the pharynx is covered with 
yellow, viscid mucus. The thyreoid is of normal size. The pericardium 
is empty, the heart small and brown. The right pleura is covered with 
fibrinous exudate, in which are miliary nodules, and in the cavity is about 
one litre of clear serum. In both lung apices are circumscribed tubercular 
foci. The peribronchial lymph glands contain caseous masses. In the 
liver are caseous nodules which have a softened, bile-stained centre. The 
capsule of the spleen contains caseous masses. The kidneys are small, 
smooth, and pale brown; in the interior are scattered small yellowish nod- 
ules. The genito-urinary mucous membranes are normal. The stomach, 
the intestines, the pancreas, and the adrenals are normal. In the spinal 
pia are occasional miliary granulations and some infiltration with turbid 
serum. 
Bacteriological Examination.—Cover-glass preparations from 
the meningeal exudate contain tubercle bacilli often in heaps of 
four to six, and usually free. No other bacteria are present. 
Plate cultures from the exudate remain sterile at the end of some Ludvig Hektoen 
days in the thermostat, but blood-serum tubes present pure growths 
of tubercle bacilli. 
The injection of 0-3 cubic centimetre of ventricular fluid through 
a small trephine opening into the subarachnoid space of a rabbit 
produced in two weeks a solitary tubercle 0-8 centimetre large in 
the subjacent brain with meningeal adhesions, accompanied with 
great emaciation, but without fever; there was no meningeal exudate 
and no admixture of other bacteria. 
Cover-glass preparations from the nasal muco-pus contain 
staphylococci, streptococci, diplococci, and occasional tubercle bacilli. 
Histological Examination.—The arterial changes in this case 
present many points of interest that may be summarized as follows; 
The serial sections through pieces of the Sylvian arteries, including 
the tubercles that seemed to sit in the arterial wall, show a distinctly 
circumscribed and focal infiltration of all the layers of the wall, with 
some caseation and considerable thickening of the intima underneath 
the endothelium (at times this is absent), often accompanied with a 
sharp, puncbed-out perforation of the elastic layer and a more or less 
precisely circumscribed infiltration in the media, the adventitial 
changes being at times marked, at times very insignificant, or even 
entirely absent (Plate YIII, Fig. 5). Now it happens that in such 
foci as these there may be a distinct outward bulging of the vessel 
wall corresponding to the infiltration in the media, the ends of the 
elastic lamina being turned outward on each side of the perforation, 
the whole representing to some extent a minute aneurism in which 
the arterial wall is more or less completely substituted by tubercu- 
lous granulation tissue. Many such peculiar foci are found not only 
in the branches in the Sylvian fissures, but also in the arteries of the 
convexity. In some places only the innermost portions of the granu- 
lation tissue (the part between the ends of the elastic lamina and in 
the intima) is caseous; giant cells are not present. Rupture with 
hsemorrhage of any such perforating focus was not found. 
Isolated intimal masses of cells without changes in the media or 
in the adventitia are also found, and at times they show distinct 
caseation ; some doubtful giant cells are also seen. 28 
The Vascular Changes of Tuberculous Meningitis 
Furthermore, the vessels present a marked endarteritis both with 
as well as without changes in the other walls, leading often to a 
more or less complete occlusion of the lumen. Occasionally the 
subendothelial intimal proliferation breaks through the elastic layer 
and spreads out between this and the media. 
A smaller series of sections through the cerebellar cortex includes 
a focus of endarteritis in a large vessel. As is usually the case, it is 
distinctly subendothelial, and the cells are mostly large and round 
with some scattered lymphocytes. A distinct intercellular substance 
is not observable. At the point where most marked it produces oc- 
clusion of one part of the lumen ; here the cells of the endothelial 
layer meet each other in the centre of the vessel. There is a very 
slight infiltration with some hyaline degeneration in the inner layers 
of the surrounding media with barely perceptible peri-arterial 
changes. There are occasional cells with two to four nuclei, but no 
distinct giant cells. 
In places where the changes are diffuse the smaller arteries are 
totally infiltrated, caseous, or hyaline. The walls of the veins are 
usually extensively infiltrated, and at times the lumen contains 
thrombotic masses. In the spinal pia there is some infiltration into 
the arterial adventitia and into the walls of veins; there are no 
special changes in the intima of the arteries. 
In all the sections from this case the only indications of giant 
cells observed after vigilant search were certain irregular masses 
with many nuclei in the intravascular foci. Tubercle bacilli wTere 
found in small numbers in the intimal proliferations, and somewhat 
more numerously in the extravascular granulation tissue. 
Case Ylll.—From the Medical Clinic of Prof. Pribram : 
Woman, aged twenty-four. 
Clinical Diagnosis.—Tuberculous meningitis ; lumbar spon- 
dylitis. Section twelve hours post mortem (June 12, 1895). 
Anatomical Diagnosis.—Obsolete tuberculosis of the peribron- 
chial lymph glands; chronic tuberculosis of the second and third 
lumbar vertebrm ; psoas abscess; universal subacute tuberculosis; 
tuberculous meningitis. Lndvig Hektoen 
29 
The body is 160 centimetres long, of feeble build and poor nourishment. 
Pale lividities posteriorly. The neck is narrow and long. The chest is 
flat and narrow. The abdomen is retracted. 
The skull is thin, 50 centimetres in horizontal circumference. The dura 
is tense and in the sinuses is fluid blood. In the meshes of the pia, espe- 
cially about the base, but also over the upper surface of the brain, is a tur- 
bid, sero-flbrinous exudate. Along the Sylvian arteries on both sides are 
innumerable minute, grayish, semi-transparent nodules, which appear to 
sit partly upon, partly in the walls of the vessels. Similar nodules are 
also found along the vessels of the convexity, the choroid plexuses, and in 
the floors of the lateral ventricles, but in much smaller numbers. Upon 
the left half of the brain are a few a little larger and yellowish masses in 
the pia of irregular form which extend into the brain substance. 
In the thyreoid gland are numerous miliary nodules. Both lung apices 
are slightly adherent. Throughout the pulmonary parenchyma of both 
sides are distributed numerous minute yellowish nodules of equal size. The 
heart is small, its muscle dark red, the valves thin. 
The peribronchial lymph glands contain calcareous and fibrous masses. 
The capsule and the parenchyma of the liver contain numerous nodules 
wlnch are also found in the spleen and in the kidneys. The genital organs, 
the stomach, the intestines, the pancreas, and the adrenals are without any 
special changes. In the bodies of the second and third lumbar vertebrae are 
caseous masses, and in the right psoas major muscle is a small abscess. The 
spinal cord and its membranes are without any changes. 
Bacteriological Examination.—Cover-glass preparations from 
the meningeal exudate contain now and then single tubercle bacilli 
and no other micro-organisms. 
Glycerin-sugar-agar plates inoculated with the meningeal exu- 
date remain sterile after some days in the thermostat. Blood-serum 
tubes inoculated with the same exudate showed pure cultures of 
tubercle bacilli. 
Histological Examination.—In some places, especially at the be- 
ginning of the Sylvian fissures as well as in the apparently some- 
what older masses upon the surface of the left hemisphere, there is 
much fibrinous exudate and diffuse cell proliferation with caseation. 
Here the smaller arteries are diffusely and wholly caseous, at times 
hyaline. The so-called hyaline degeneration may involve the whole 
or part of the wall, usually the media, in the form of a homogeneous 
ring which stains a bluish-violet tinge with hsematoxylin (Delafield’s) 
and bright red with Yan Gieson’s stain. Hyaline masses of irreg- 
ular shape are also found in the other coats of the vessels and in the 30 
The Vascular Changes of Tuberculous Meningitis 
extravascular infiltration. The larger arteries frequently show a 
uniform and intense involvement of the adventitia and of the outer 
layers of the media; in the inner layers of the media the infiltration 
is at times diffuse, the cells being rather sparsely scattered about; at 
other times the infiltration is more focal and denser, with occasional 
cell accumulations between the elastic layer and the media. There 
is usually, but not constantly, a diffuse and pronounced subendo- 
thelial proliferation of large and small round cells, lying sometimes in 
a granular, sometimes in a slightly tibrillated matrix ; frequently there 
are more nodular cell masses, in the centre of which is some degen- 
eration, and also probable necrotic giant cells. Here and there the 
elastic layer is split up by infiltrating cells. Lymphoid tubercles with 
giant cells are also found upon the intima of the larger arteries, 
with but moderate general endarteritis, the media and the adventitia 
being the seat of a not very marked infiltration. 
Further out in the Sylvian fissures the arteries present circum 
scribed nodular cell infiltration with some degeneration which in- 
volves all the coats in a fairly equal degree. More or less endarteritis 
is present here also. In the smaller arteries are observed focal intra- 
vascular and extravascular changes usually connected, as it were, by 
a mild infiltration through the media, but frequently entirely inde- 
pendent of each other. 
Serial sections through minute masses in the pia over the brain 
surface show the cell mass to be connected with a small artery, one 
segment of its wall being completely involved in the tubercle, which 
seems to arrange itself in a concentric manner about this part of the 
vessel. Some slight and diffuse endarteritis is also present. In the 
centre of the tubercle the degeneration seems about as far advanced 
in the inner as in the outer parts of the wall involved, but at the 
periphery the degeneration is most marked in the peri-arterial infil- 
tration. 
The beginning of such foci as the last is probably illustrated in 
the small, circumscribed, subendothelial, intiraal proliferations with 
giant cells accompanied with only slight infiltration into the media 
and the adventitia, and with the formation of epithelioid cells in the Ludvig Hektoen 
31 
peri-arterial lymph spaces, the intimal changes being by far the most 
pronounced which are occasionally found in the pial arteries of the 
convexity. 
The veins are usually the seat of a diffuse infiltration; at times 
an apparent isolated endophlebitis is observed, but sooner or later 
such veins present points where the whole wall is involved. 
Tubercle bacilli are present in some numbers in the endovascular 
foci, but most numerously in the peri-arterial infiltration. 
Case IX.—From the Psychiatric Clinic of Prof. A, Pick : Man, 
forty-six years old. 
Clinical Diagnosis.—Delirium; meningitis cerebro - spinalis. 
Section ten hours after death (May 21, 1895), 
Anatomical Diagnosis.—Chronic tuberculosis of the lung apices 
and of the peribronchial lymphatic glands; tuberculous meningitis; 
universal miliary tuberculosis. 
Strongly built man with well-developed musculature, the body being 
174 centimetres long. Rigor mortis strong. The pupils are equal, the 
thorax oval, and the abdomen retracted. 
The skull is 56 centimetres in horizontal circumference, rather thick, 
and its internal surface somewhat roughened. The dural sinuses contain 
a moderate quantity of fluid blood. The internal meninges are rather pale; 
about the base the meshes contain turbid serum. Along the Sylvian arteries 
are numerous grayish nodules the size of millet seeds. Similar nodules 
are also present upon the upper surface of the cerebellum. The brain 
substance is moist. In the neighbourhood of the dilated ventricles, which 
are filled with turbid fluid, the substance is softened. The mucous mem- 
brane of the organs of the neck is pale. The thyreoid is rattier small. 
In the apices of both lungs are older caseous and calcareous masses, sur- 
rounded by dense cicatricial tissue. The parenchyma contains every- 
where numerous miliary, grayish-yellow nodules. The peribronchial 
glands are partly caseous. The pericardium contains a small quantity of 
serum. The heart is of normal size, pale, the valves thin. The liver and 
the spleen are the seat of innumerable miliary tubercles. The kidneys are 
of usual size, and the cortex contains numerous miliary nodules. The gen- 
ital organs, the stomach and the intestines, the pancreas, and the adrenals 
show no pathological changes. 
Bacteriological Examination.—Cover glasses from the menin- 
geal effusion contain a very few tubercle bacilli, but no other 
bacteria. 32 
The Vascular Changes of Tuberculous Meningitis 
Glycerin-sugar-agar plates from the same exudate remain 
sterile. The nose conld not be examined. 
Histological Examination.—There is a moderately extensive 
extravascnlar infiltration, with some caseation, but no giant cells. 
The adventitia of the smaller arteries is diffusely and densely infil- 
trated with epithelioid cells and small round cells. At times the 
media remains normal, at other times it is infiltrated, but in this 
case there is no hyaline degeneration of the media observable. In 
these arteries there is also a diffuse subendothelial proliferation 
that sometimes nearly fills the lumen of the vessels. Small arteries 
diffusely involved and changed into miliary tubercles are also 
present. 
In the medium-sized arteries there may be considerable endarter- 
itis, occasionally leading to a nearly complete occlusion of the lumen, 
without changes in the other coats (Plate YIII, Pig. 3), except occa- 
sional foci in the periphery of the adventitia; then again the en- 
darteritic changes may be associated with more extensive and dense 
adventitial proliferation. 
The large arteries present occasional distinct tubercles located 
underneath the endothelium, which may be absent at but one 
point corresponding to which there is no thrombosis. Such a 
tubercle is usually accompanied with some endarteritis which ex- 
tends half way or so around the vessel. At various points the 
cells of the tubercle may pass through the elastic lamina and in- 
filtrate the media. In the adventitia there may be some prolifer- 
ation corresponding to the tubercle, but only of slight degree. In 
places the subendothelial intimal proliferation commences with 
the formation of cells upon the elastic lamina; in some of these 
cells the nucleus is large and swollen; distinct karyokinesis is 
not found. In some places the larger arteries present a focal 
chronic thickening of the intima which takes no part in the acute 
changes. 
The veins are usually the seat of circumscribed or diffuse infil 
tration that always is connected with neighbouring foci. 
There were no giant cells in this case. Ludvig Hektoen 
33 
Tubercle bacilli were found in fair numbers in the peri-arterial 
infiltration and in the walls of small arteries. 
Before considering the special arterial changes in this series of 
cases of tuberculous meningitis a few remarks concerning the bacte- 
riological examinations are necessary. 
Of the nine cases, but one presented a mixed infection due to a 
staphylococcus, which was present in small numbers in the meningeal 
exudate and gave rise to three colonies upon the plate cultures made 
from the fluid. 
The microscopic examination does not indicate positively that 
the presence of this staphylococcus had any distinctly recognisable 
effects upon the intensity or the character of the inflammatory 
changes of the case in which it was found. 
Yery likely the meningeal infection by this staphylococcus took 
place from the nose, in the mucus of which were a large number of 
similar staphylococci. The possibility of a general infection of the 
blood from some other source than the nose can not be denied in 
the absence of decisive investigation on this point. 
That only one case of nine should show a mixed infection is a 
little unexpected in view of the results obtained by Babes, who 
examined seventeen cases of acute tuberculous meningitis bacterio- 
logically and found, in addition to the tubercle bacillus, twice the 
micrococcus lanceolatus, twice the streptococcus, twice staphylococci, 
and in two cases two separate varieties of pathogenic bacilli, making 
eight of the seventeen cases instances of mixed infection. 
Pasquale also found and isolated the streptococcus pyogenes in 
one case of tuberculous meningitis and in one case of tuberculosis of 
the ependyma. 
In five of nine cases a superficial examination of the mucus and 
muco-pus of the nose for tubercle bacilli by means of the staining 
method gave a positive result in two instances (Cases I and 
YII). The indications are, then, that a more thorough search, ac- 
companied with inoculations into susceptible animals, would have 
given more numerous positive results. 34 
The Vascular Changes of Tuberculous Meningitis 
The tubercle bacilli present in the two instances may have found 
their way into the nose from the tuberculous foci present in the 
lungs in both instances, or through inhalation from the outside 
(Straus), or from the meningeal exudate in which they are present 
in cases of tuberculous meningitis. 
Gradinego found in this disease tubercle bacilli in sections from 
the nerves that pass through the internal ear and also in the pharyn- 
geal mucus in the neighbourhood of the openings of the Eustachian 
tube, and he considers that they pass out from the subarachnoid 
space by the route thus indicated. 
In three cases cultures of tubercle bacilli were obtained by 
merely inoculating a drop or two of meningeal fluid upon glycerin 
agar or blood serum. 
It is consequently easy to secure cultures of bacilli from the 
lesions of tuberculous meningitis. This is shown also von Wunsch- 
heirn, who obtained cultures three times out of five attempts by 
inoculating the small nodules of acute tuberculous meningitis di- 
rectly on serum. 
The results of the histological examination of the instances of 
tuberculous meningitis that have been detailed in the foregoing 
pages demonstrate that in every case extensive vascular changes of 
various kinds were present. 
The fact that in the arteries not only the adventitia, but also the 
media, and even the intiraa, present frequent and marked tubercu- 
lous lesions, should naturally attract much attention. 
The arterial tuberculosis presents itself for discussion not only 
from the essentially histological point of view, but requires con- 
sideration also with more particular reference to the mode of the 
invasion of the arterial wall, whether from within or from without, 
and to the relation in each instance of the arterial changes to the 
general meningeal infection. 
With these problems in sight, the essential lesions of the various 
cases may be summarized in this general way: 
Cases I, 11, 111, and IY are accompanied with one or more Ludvig Hektoen 
35 
chronic meningo-encephalitic foci. In Case I there is a caseous 
nodule one cubic centimetre large along the anterior margin of the 
left cerebellar hemisphere, and connected with the pachymeninx; in 
Case II are numerous pea-sized nodules in the cortex connected with 
the pia, and in Case 111 many larger and smaller caseous masses in 
the brain, cerebellum, and pons; in Case IV the beginning of the 
Sylvian arteries and of the arteries of the corpus callosum is sur- 
rounded by chronic meningo-encephalitic masses. 
In the remaining instances larger chronic, tubercular foci are 
not present in the brain. 
In all the cases there were multiple chronic, caseous masses in 
various parts of the body, the peribronchial lymphatic glands, for 
instance, being more or less involved in every ease. 
In three instances (111, VI, and IX) there was a general acute, 
miliary tuberculosis, and two other cases (V and VIII) presented a 
universal subacute tuberculosis. 
In Cases I and 111 the proliferation and degeneration, as far as 
the arteries are concerned, involve principally the adventitia and 
the media. In some places there is a diffuse affection of the whole 
wall, and very frequently is this the case in the smaller arteries. 
Both present also some subendothelial, intimal proliferation, but the 
changes in the outer walls are, altogether, the predominating. 
In Case II the Sylvian artery presents a circumscribed infiltration 
that reaches the intirna, and the smaller branches in the Sylvian 
fissures are the seat of an endarteritis without marked adventitial 
or medial changes. 
In Case IV the entire walls of the larger basal arteries are infil- 
trated and caseous, so that the structure is not recognisable, and 
degenerated cell masses are found upon the intirna that may have 
been miliary tubercles. Otherwise a thorough examination fails to 
demonstrate intimal tubercles or giant cells in any one of these four 
instances. 
In Case V, however, the arteries of the corpus callosum present 
distinct intravascular tubercles with diffuse infiltration, caseation 
and giant cells; extensive changes are present in the media and 36 
The Vascular Changes of Tuberculous Meningitis 
the adventitia, as well as in the surrounding tissues. Small 
caseous masses in the pia are closely bound to the arterial 
walls. 
In this case the gelatiniform, sero-fibrinous exudate character- 
istic of tuberculous meningitis was not present. Nevertheless, it does 
not seem quite correct to regard the process as a subacute miliary 
tuberculosis of the pia exclusively, because the turbid meningeal 
fluid contains many epithelioid cells, leucocytes, and also tubercle 
bacilli. The diffusion of the bacilli in the meningeal fluid may have 
occurred very shortly before death, and the gross inflammatory 
products may have been absent on this account. 
In Case YI the intravascular changes are best marked (Plate VIII, 
Figs. 1, 2, and 4). They consist of a diffuse endarteritis that at times 
leads to occlusion of the lumen, especially in the smaller arteries. 
Giant cells and typical tubercles occur in the endarteritic districts. 
Isolated intimal tubercles are present. The diffuse intimal prolifera- 
tion and the intimal tubercles occur as the only disease of the arte- 
rial wall as well as in association with changes of variable intensity 
in the other coats. 
Cases VI, VIII, and IX are really identical as regards these 
lesions, the only differences being those of degree. 
Case VII is characterized by sharply circumscribed infiltrations 
through the whole thickness of the arterial wrall that often lead to 
small aneurisraal bulgings (Plate VIII, Fig. 5). Only the innermost 
layers of this granulation tissue may show caseation. Isolated 
masses of cells, at times caseous, are also found upon the intima 
without any changes in the other walls. In addition there is pres- 
ent a diffuse endarteritis, at times associated with changes in the 
adventitia and the media, at times being the only lesion present in 
the whole arterial wall. 
In Case VIII is an endarteritis with indistinct tubercles that 
show signs of caseation, associated with diffuse and extensive changes 
in the media, but there are also intimal tubercles with but slight 
alterations in the other walls, and the mode of origin of the minute 
granulations connected with the arteries of the pia over the convexity Ludvig Hektoen 
37 
can be traced with reasonable certainty to primary subendothelial 
proliferations in the intima which contain giant cells. 
In Case IX are distinct intimal tubercles without giant cells but 
with caseation accompanied with a more diffuse endarteritis and 
slight infiltration of the media and the adventitia. In the smaller 
arteries are very diffuse changes. 
In the sections from all the cases tubercle bacilli were present in 
small numbers in the intimal lesions, in the lumen of infiltrated 
veins and smaller arteries and their walls, and in much larger num- 
bers in the adventitial proliferation. The infiltrated part of the 
Sylvian artery in Case IY contained bacilli in great numbers. 
The demonstration of tubercle bacilli, free and intracellular, in 
the meningeal exudate in the majority of the cases has been con- 
sidered. 
In such cases as all of these under consideration at the present 
time the extensive and multiple tuberculous processes in various 
organs indicate clearly enough that tubercle bacilli must have gained 
entrance into the general circulation. This circumstance alone 
would be good reason for regardin the tuberculous meningitis as of 
a hsematogenous origin. In addition, the extensive lesions of the ar- 
terial intima in all these cases, especially when studied in their rela- 
tion to the changes in the other layers of the arterial wall, furnish 
direct anatomical evidence that bacilli were deposited upon the in- 
tima from the blood, and that the meningitis positively resulted from 
blood infection. 
It is true that in the three first instances described distinct in- 
timal tubercles with giant cells were not found, and that the changes 
in the adventitia and in the media of the larger arteries predomi- 
nate over those in the intima, the latter consisting in the main of a 
more diffuse subendothelial proliferation. It might consequently be 
said that perhaps the chronic tuberculous masses in the brain and in 
the meninges, which were present, more likely furnished the source 
of the meningeal invasion in these cases. 
In no one of the three cases, however, does the distribution of 
the characteristic lesions indicate that the meningitis developed from 38 
The Vascular Changes of Tuberculous Meningitis 
the chronic cerebral foci. It matters not where the old caseous 
masses may be situated, the acute lesions, the miliary tubercles, and 
the exudate are found best marked around the arteries of the Syl 
vian fissures and of the corpus callosum. The meningeal changes 
do not radiate in all directions from the chronic foci, but they have 
that general distribution with the special predilection for the Sylvian 
arteries which is so characteristic of blood-borne infection. 
When the intravascular changes in these cases are studied in the 
light in which such lesions are presented to view in the remaining 
instances, then it becomes plain that arteries, especially small ones, 
the entire wall of which is infiltrated and caseous, may just as well 
have been invaded from within as from without, and that an endar- 
teritis which is not accompanied with very extensive changes in the 
media and the adventitia is most likely the primary arterial change. 
The occasional presence of tubercle bacilli in the lumen and in the 
wall of smaller arteries (Cases I and III) also point to infection by 
way of the blood. 
The gross distribution of the meningeal lesions, then, the endar- 
teritis present in all the three cases, though in varying degree, as 
well as the diffuse involvement of arteries, especially the smaller, 
afford substantial anatomical reasons for regarding the meningitis as 
of hsematogenous origin, and the arterial changes presented as in 
part at least the direct result of this mode of invasion. 
In Case IV the intense involvement of the large basal arteries in 
the chronic leptomeningeal process may be taken to indicate that 
the latter began in the arterial wall, but the local changes are in a 
measure too diffuse and the degeneration too far advanced to form 
any definite idea as to the exact order of the development of the 
lesions. 
The situation of the chronic meningeal foci in this case, associ- 
ated as they are with such diffuse arterial changes in the neighbour- 
hood, suggests the possibility that these masses furnished at one and 
the same time the source for an arterial dissemination of the bacilli 
into the leptomeninx as well as of an infection of the pial lymph 
spaces. Ludvig Hehtoen 
39 
In the remaining cases the arterial lesions indicate with great 
certainty that an invasion of the wall frequently occurred from 
within. While the wall in these cases also presents diffuse changes— 
changes that especially involve the adventitia, from which they may 
spread inward—there are also very extensive and important changes 
in which the intima plays the essential part (Plate VIII, Figs. 1, 2,3, 
4, and 5). 
As already shown, tubercles in the intima may occur in asso- 
ciation with more or less diffuse changes in the other coats, accom- 
panied with an extensive endarteritis, or they may occur without 
any other changes of the arterial segment in the intima of which 
they are situated (Plate VIII, Fig. 4). Foci of granulation tissue 
that perforate the arterial wall more or less sharply also seem to 
begin in the intima (Case VII, Plate VIII, Fig. 5). 
Associated with these typical tuberculous changes is an endar- 
teritis that may occur independently or be connected with infiltration 
in the media and the adventitia. The presence of this endarteritis 
without changes in the other layers of the wall, but being confined 
to the internal surface of an artery throughout its entire extent,* 
shows conclusively that this very interesting form of intravascular 
lesion in tuberculous meningitis may be primary and due to inflam- 
matory agents circulating in the blood (Plate VIII, Figs. 1, 2, and 3j. 
Bearing the fact in mind that such extensive and undoubtedly 
primary intimal lesions may be present in tuberculous meningitis, it 
will become exceedingly difficult, if not entirely impossible, to decide 
where the process may have had its point of origin in the case of 
more or less diffuse involvement of the arterial wall when associated 
with endarteritis. 
On this account it would be unsafe to regard the changes of the 
arterial wall to proceed always from without inward, as Guarnieri 
concluded. Even the greater intensity and the apparently greater 
* By means of the serial sections it was possible to establish the exact relations that 
the changes in the arterial wall may bear to each other when not too far advanced. The 
actual existence of an isolated intimal tubercle or of a limited focus of endarteritis, for in- 
stance, could only be demonstrated by means of serial sections of the whole extent of the 
artery involved. 40 
The Vascular Changes of Tuberculous Meningitis 
age, as determined by degeneration, of lesions in the adventitia and 
the media can not he regarded as absolute criteria as to the point of 
primary attack of the arterial segment, because there is occasionally 
found a district of hyaline degeneration of the inner part of the 
media immediately underneath intimal foci that present but slight 
retrogressive changes, no other lesions of the wall being visible. 
Degeneration can consequently develop in the media secondarily to 
well-preserved adjacent foci of proliferation in the intima. 
Invasion of the media and of the intima from without certainly 
occurs in tuberculous meningitis as well as elsewhere, as, for in- 
stance, in the lungs, and with great frequency. This is shown best 
by the presence of diffuse or circumscribed adventitial proliferation 
that gradually extends into the media and reaches the intima per- 
haps only at one point. In this "way an endarteritis due to direct 
extension from without may arise and extend along in the intima. 
It seems, however, that an endarteritis distinctly traceable from 
without rarely reaches the extent of the primary endarteritis. Inti- 
mal tubercles with giant cells were not found upon the arteries in 
which it could be shown with certainty that the process invaded the 
arterial wall from without. In connection with this, attention is 
called to the fact that in many cases the only giant cells found after 
vigilant search were those in the endarteritic foci. 
Whether or not tuberculous processes confined to the adventitia 
can give rise to an acute intimal proliferation, without direct exten- 
sion of the inflammation through the media, hardly needs discussion. 
Chronic inflammatory processes in the neighbourhood of arteries are 
often stated to call forth an obliterating endarteritis (see note, page 
119). In acute tuberculous meningitis one very often observes exten- 
sive changes in the adventitia associated with proliferative changes 
of variable extent in the intima, the media remaining unchanged. 
Whether the changes in the outer and the inner layers bear any 
direct and intimate relations to each other under these circumstances 
must be left undecided for this one reason, if for no other—namely, 
the impossibility of excluding a direct hsematogenous origin of the 
endarteritis. The same consideration applies to the obliterating, Ludvig Hektoen 
41 
subendothelial intimal proliferation observed by Weintraud in more 
chronic meningo-encephalitic tuberculous foci, and attributed by 
him, in accordance with the views of many writers, to influences act- 
ing upon the intima from without; the intimal lesions may have 
been caused by direct infection from the blood. 
It is self-evident that following the total invasion of an arterial 
wall from without, a local diffusion of bacilli might occur in the cor- 
responding branches with, perhaps, a secondary endarteritis due to 
implantation of the bacilli upon the intima. And of course the same 
manner of propagation may follow primary intimal foci. In either 
case a destruction of the endothelium would be most favourable for 
the admission of bacilli into the blood current, and at such times 
thrombosis may hinder the process from spreading in this manner. 
The tuberculous endarteritis that has been described as occurring 
primarily and independently of changes in the outer arterial coats 
demonstrates that tubercle bacilli are implanted in the intima. The 
intact endothelium usually present shows that the bacilli must reach 
the subendothelial layer at once after passing through the endothelial 
lining. 
Attention may be called to the fact that the arteries in the Syl- 
vian fissures present probably the greatest degree of endarteritis. 
This fact may be accounted for by the favourable conditions of- 
fered by these vessels for the localization of the microbes. In other 
wrords, it would seem that to some extent the same conditions obtain 
in the localization of the bacilli as are so frequently observed to 
be operative in connection with the import of emboli into the brain. 
The marked degree of primary endarteritis in the Sylvian arteries 
explains also, to some extent at any rate, the relatively greater de- 
velopment of the adventitial and extravascular changes in the Sylvian 
fissures than elsewhere. 
The histological examinations show that the muscular coat of the 
large as well as the small arteries is the frequent seat of infiltration 
and caseation that may have their origin in the adventitia or in the 
intima, according as the invasion occurs from within or from without. 
Appearances indicating the origin of new cells from the muscle 42 
The Vascular Changes of Tuberculous Meningitis 
fibres, which Rindfleisch is inclined to believe that lie has observed, 
were not present in any of these instances, in all of which the medial 
changes seemed to be the result of a direct extension of the process 
in the adventitia or in the intima. 
When the infiltration invades the media from the intima, the 
elastic membrane always presents evidences of a more or less direct 
destruction of its continuity (Plate YIII, Figs. 4 and 5). At times it is 
split up by invading cells that seem to be in the act of passing through 
it. When the process is further advanced it may present a sharply 
cut defect occupied by granulation tissue or by caseous material. At 
other times the elastic membrane as well as the inner part of the 
media undergo a peculiar hyaline degeneration underneath foci of 
proliferation in the intima. In Case VII, in which the arterial walls 
present numerous aneurismal bulgings at the seat of perforating foci 
of tuberculous infiltration, the ends of the perforated elastic layer 
are bent outward. 
In the descriptions of the microscopical changes frequent refer- 
ence is made to the infiltration and caseation of the whole wall, 
especially in smaller arteries, and to a more or less extensive hyaline 
degeneration whose favourite seat seems to be the media, but which 
may occur in any part of the vessel wall as well as in the extra- 
vascular infiltration. This hyaline degeneration was observed in the 
media as the only change in the whole wall in addition to focal or 
diffuse endarteritis. 
This peculiar hyaline necrosis in tuberculous meningitis has been 
fully described by Guarnieri, according to whose opinion the hyaline 
substance represents the end products of degeneration in the tubercle 
cells, the muscle cells, and the exudate. 
The pial arteries in tuberculous meningitis consequently pre- 
sent excellent opportunities for the study of hyaline degeneration 
which here seems to appear very rapidly under the influences of 
the acute inflammatory process. 
In addition to the arterial changes, those in the veins merit at- 
tention (Plate YIII, Fig. 6). In all the instances the veins, large and 
small, show diffuse or circumscribed infiltrations of the walls that Ludvig Hektoen 
invariably proceed from changes in the neighbourhood, as, for in- 
stance, in an adjacent artery. Giant cells frequently occur in the 
infiltrated walls often lying next to the blood stream. Caseation and 
disintegration are also found, and frequently the lumen is throm- 
botic. Tubercle bacilli are also present in the infiltrated walls. 
No doubt general miliary tuberculosis may develop secondarily 
to tuberculous meningitis on account of a dissemination of tubercle 
bacilli from these extensive and constant lesions of the pial veins. 
Tedeschi found that a general infection occurs very rapidly after the 
subdural inoculation of rabbits and other animals with tuberculosis. 
All authors emphasize the prominent part played by the adven- 
titia in the formation of the tubercles and more diffuse infiltrations 
in tuberculous meningitis. It is in the lymph spaces of this layer 
of the arterial wall that the tubercle bacilli appear to find the most 
favourable conditions for rapid growth. Especially in the early part 
of the process large cells, often containing tubercle bacilli can be 
seen filling the adventitial lymph spaces. Some of these cells may 
be carried away with the lymph stream, and, as the cells fall to 
pieces, the bacilli are set free to start new centres of proliferation. 
Thus in Case Y the presence of many bacilli in the epithelioid cells 
of the subarachnoid fluid, and also in similar cells in the lymph spaces 
about the arterial tubercles, shows most conclusively the manner in 
which the bacilli may be diffused in the subarachnoid space from 
adventitial foci. 
It will, of course, be recollected that the lymph spaces of the 
adventitia of the arteries can be injected from the subarachnoid 
space (Stohr). 
Regarding the further evolution of the lesions of tuberculous 
meningitis, it may be said that the accumulation of exudate contain- 
ing bacilli in the large lymph cisterns of Key and Retzius, in the 
Sylvian fissures, and at the base, is certainly most favourable for the 
development of extensive extravascular lesions in these localities. 
The spread of the bacilli from the adventitial lymph spaces 
throughout the subarachnoid effusion may lead to a spinal leptomen- 
ingitis. The latter was present in four out of the five of these cases 44 
The Yascular Changes of Tuberculous Meningitis 
in which the spinal cord was examined—namely, in Cases I, 111, IY, 
and YII—and in all instances the arterial lesions pointed to a lymph- 
ogenous invasion. An infection of the spinal pia through the blood 
is, of course, possible, but in our cases the arterial lesions do not in- 
dicate that such was the case. 
The cerebro-spinal fluid may also carry the bacilli into the lymph 
spaces of cranial as well as of spinal nerves, where they may cause an 
interstitial (tuberculous) neuritis, as shown by Schultze with refer- 
ence to spinal nerves, by Kahler in case of the oculo-motor nerve, by 
Gradinego as regards the nerves that pass through the middle ear, and 
by Deutschmann in case of the optic nerves in rabbits, in which he 
produced experimental tuberculosis of the brain and its membranes. 
From the subarachnoid space the bacilli may also And their way 
into the nose and the pharynx, as already pointed out. 
The relation of the changes in the intima observed in these cases 
to the changes in the other coats has been explained. It has been 
emphasized that the intimal changes are of comparatively slight 
degree, and without definite tubercles or giant cells, in those places 
where it can be definitely shown that the invasion of the artery occurs 
from without; that in the case of total infiltration and caseation of 
an arterial segment no opinion can be formed as to the order of the 
development of the lesions; that intimal proliferation, often asso- 
ciated with giant cells, distinct tubercles, and caseation, and without 
extensive confusing changes in the media and the adventitia, is posi- 
tive anatomical evidence of the implantation of bacilli (which may 
be present in these lesions) from the blood. 
As already pointed out, Huguenin, Huettenbrenner, Cornil, and 
Hirschberg have also described similar intravascular tuberculous 
lesions in the pia, and have expressed practically the same views as 
the preceding concerning the signification of such lesions as regards 
the mode of infection. 
Tuberculous changes in the intima which are susceptible of the 
sole explanation that they are the direct result of the import of the 
bacilli by the blood, were found more or less clearly marked in all 
the nine cases of this series, and in some cases—as, for instance, in Ludvig Hektoen 
Case Yl—the intravascular changes are almost as extensive and as 
pronounced as the extravascular. 
The general conclusion is consequently warranted that in tuber- 
culous meningitis of blood-borne infection an unexpectedly frequent 
and significant localization of the bacilli occurs upon the intima of 
pial arteries in addition to that in the arterial adventitia. 
Experimental tuberculous meningitis has been studied by Deutsch- 
mann, who investigated.the relation between miliary tuberculosis of 
the brain and its membranes and affections of the eyes after inject- 
ing tuberculous material underneath the skull of young rabbits; by 
Daremberg, who produced tuberculous meningitis by the injection 
of pure cultures underneath the skull of rabbits; and by Tedeschi, 
who injected tuberculous material into the cranial cavity and spinal 
canal of eighty-five animals of various kinds. In addition to pro- 
ducing a meningo-myelitis and a meningo-encephalitis as well as 
diffuse miliary tuberculosis, the last-named writer found that the in- 
oculation of tubercle bacilli into the nervous centres of animals re- 
sulted in a marked increase of virulence on the part of the bacillus. 
This virulence became normal again after passing the bacilli through 
the body of guinea pigs. 
Inasmuch as there were no experiments in which the attempt had 
been made to produce tuberculous meningitis in the manner in which 
the disease nearly always develops in man—namely, through arterial 
infection—a series of experiments with this object in view were com- 
menced. These investigations are as yet incomplete ; but as the re- 
sults already obtained in a measure bear upon the conclusions ex- 
pressed as regards the tuberculous endcirteritis that has been described, 
the report of the following experiment may be introduced : 
May 16, 1895. Injection of OT cubic centimetre of a bouillon 
suspension of a glycerin-agar culture of tubercle bacilli into the left 
carotid artery of a large rabbit. 
The carotid was ligated above and below the point of punc- 
ture. 
Soon after the operation the animal began to emaciate. Shortly 46 
The Vascular Changes of Tuberculous Meningitis 
before it was killed the media of the left eye became turbid; there 
was some pericorneal injection and turbid conjunctival secretion. 
June sth, 6 p. m., killed. 
Section.—Pronounced emaciation. The media of the left eye 
turbid. There is no increase in the amount of cerebro-spinal fluid, 
and the pia mater is everywhere transparent and thin. Along the 
vessels of the convexity of the left hemisphere, especially over 
the posterior half, are numerous minute grayish nodules of varying 
size, the largest being perhaps one millimetre in diameter. There 
are no visible nodules in the pia over the right hemisphere, over 
the cerebellum, the bulb, or the base of the left hemisphere. 
There are numerous miliary nodules in the liver and some in the 
spleen, but not in any other organs. The left carotid, being cut 
across between the two ligatures a little above the clavicle, shows 
that the ends are filled with a whitish granular mass. Immediately 
above the upper ligature the vessel is surrounded by a flat, oval 
caseous mass one centimetre in its greatest diameter. 
Microscopic Examination.—After fixing in sublimate and stain- 
ing on the slide with hsematoxylin and carbol-fuchsin, sections 
through the meningeal nodules and the subjacent cortex show a 
dense infiltration of lymphoid cells around small granular masses, 
containing tubercle bacilli, which seem to occupy the interior of 
small arteries, the walls of which are entirely converted into granu- 
lation tissue. Sometimes the granular mass, including the bacilli, 
becomes infiltrated with nuclei and assumes an appearance not un- 
like giant cells. At the periphery of such nodules the lymph spaces 
are loosely filled with cells, but bacilli are seldom found except in 
the central part of the tubercles. 
The interior of the left hemisphere contains a large number of 
minute foci of granulation tissue in which may be giant cells and 
tubercle bacilli, the latter embedded in granular masses. 
The nodules in the liver are miliary tubercles. The ciliary body 
of the left eye contains miliary tubercles with giant cells located 
in the vicinity and about the arteries. The anterior and posterior 
chambers are filled with granular material. Ludvig Hektoen 
47 
This experiment shows that- a meningeal and cerebral miliary 
tuberculosis can be produced in rabbits by injecting bacilli into the 
carotid—i. e., through direct hsematogenous infection. The resulting 
tubercles develop in connection with the smaller arteries. In the 
experiment described the lesions were too far advanced to afford 
any definite observations as to the early histogenesis of the process. 
In the foregoing has been described a tuberculous endarteritis 
the histogenesis of which presents several points of interest. 
The histological appearances may be briefly recapitulated as 
follows: In addition to intimal tubercles there occurs a more 
or less extensive endarteritis, which reaches its greatest degree of 
development in the medium-sized or smaller arteries in which it 
frequently leads to great narrowing and almost complete oblitera- 
tion of the lumen. That this endarteritis may be primary and not 
due to extension from the outside is readily shown by serial sections 
extending through endarteritic foci in which the arterial wall is 
otherwise normal (Plate YIII, Figs. 1, 2, 3, and 4). 
In all well-preserved specimens the proliferation—which consists 
of epithelioid cells with but occasional lymphocytes and polynuclear 
leucocytes and, quite rarely, rnultinucleated giant cells (Plate YIII, 
Fig. 2)—is invariably subeudothelial, the cell layers lying between 
the elastic lamina and the intact but loosened and elevated endothe- 
lium (Plate YIII, Figs. 1, 2, and 3). Frequently characteristic inti- 
raal tubercles develop in this proliferation, and as they become case- 
ous the endothelium over them may disappear (Plate YIII, Fig, 4). 
In the early stages the endarteritis presents itself in the form 
of small nodular accumulations of cells that present unmistakable 
signs of active proliferation underneath an intact endothelium, 
which is lifted up into folds. In many places the subendothelial 
cells penetrate the elastic membrane and invade the muscular coat 
to a greater or less extent. 
Similar appearances, though less marked, are found in arteries 
that are invaded by cell infiltration from the adventitia. 
The subendothelial intimal proliferation may present caseation 48 
The Vascular Changes of Tuberculous Meningitis 
and hyaline degeneration. Only occasional tubercle bacilli are found 
in and among the epithelioid and other cells. 
The endothelial cells remain entirely passive and present no ap- 
pearance of active proliferation, the lining being mechanically lifted 
away, as it were, by the increasing cell accumulation underneath. 
At times the endothelial lining becomes disarranged, especially when 
the endarteritis is very marked. 
The origin of the epithelioid cells that in the main constitute 
the subendothelial proliferation is a question of great interest. 
Nearly all the authors that have described endarteritic changes 
in tuberculous meningitis refer to these cells as the results of multi- 
plication on the part of the endothelium. Huguenin, Guarnieri, 
Brodowski, Baumgarten, ITirschberg—all seem to take this view. 
Baumgarten, in his classical research upon the histogenesis of 
tubercle, also refers to certain changes in the intima in experimen- 
tal pulmonary tubercle as due to endothelial proliferation. 
Metschnikolf assigns to the endothelial cells an active role in the 
formation of hepatic and pulmonary tubercle. 
This is not the place to enter into a detailed discussion of the 
origin of epithelioid cells in general. The views of Baumgarten 
and of Metschnikoff are familiar enough. The recent studies by 
Kostenitsch and Wolkow and by Borel of the development of experi- 
mental tubercle treat of the various phases of this question with 
considerable minuteness of detail. 
While it is evident that the morphology of the epithelioid cells in 
the endarteritis of tuberculous meningitis can not explain their na- 
ture or declare their derivation, it seems that their origin from the 
endothelial cells can be positively excluded on account of the condi- 
tion of the endothelial lining itself. Were the epithelioid cells in 
question produced by proliferation of the endothelial cells, then the 
endothelial lining would be disarranged, and the subendothelial pro- 
liferation wrould no longer be limited on the side of the lumen by a 
single layer of typical endothelial cells that show no signs of multi- 
plication whatsoever. The division of a single endothelial cell into 
two would certainly result in some displacement of the dividing cell Ludvig Hektoen 
49 
with reference to the other cells in the endothelial lining. Baum- 
garten’s figure of a young metastatic tubercle in the lung shows, on 
the other hand, like the sections of the tuberculous endarteritis, an 
artery with a mass of epithelioid cells between an unbroken and un- 
changed row of single and typical endothelial cells and the elastic 
layer. Near by is represented karyokinesis in what may be the un- 
changed endothelium, but the karyokinetic figure may also be in a 
subendothelial connective-tissue cell. 
For these reasons it may be concluded that the endothelial cells 
take no active part in the production of epithelioid cells in tuber- 
culous endarteritis; on the other hand, it would seem that the endo- 
thelial cells remain not only passive, but even resistant to the bacilli 
and their products, because the lining remains intact and unbroken 
until the proliferation almost fills the entire lumen. When casea- 
tion occurs, however, then the endothelial cells disappear. 
As already stated, the bacilli must apparently pass through the 
endothelium and into the subendothelial layer of connective tissue, 
which, from the early appearances of the endarteritic proliferation, 
most likely gives rise to the epithelioid cells. 
Conclusions. 
1. In tuberculous meningitis there is a tuberculous endarteritis 
characterized by the formation of intimal tubercles and a diffuse 
subendothelial, intimal proliferation due to implantation of tubercle 
bacilli from the blood. From the endarteritis the infiltration may 
spread into the muscular coat and the adventitia, and the whole wall 
may undergo caseous and hyaline degeneration. 
2. Tuberculous proliferation in the adventitia may invade the 
media and the intirna, and the whole wall of the arterial segment 
may undergo degeneration. 
3. The veins are constantly the seat of more or less extensive in- 
filtration, which always results from adjacent extravascular or arte- 
rial foci. 
4. The epithelioid cells of the subendothelial, tuberculous intimal 50 
The Vascular Changes of Tuberculous Meningitis 
proliferation are most likely derived from the subendothelial layer 
of connective tissue and not from the endothelial lining. 
There remains the pleasant duty of expressing the warmest thanks 
to Prof. Chiari for his constant aid and advice during the progress 
of the work embodied in this article. 
Description of Plate VIII. 
Fig. I.—Subendothelial proliferation of epithelioid cells without any changes in the 
other coats. Note the intact endothelium. From Case YI. Zeiss, Obj. E, Oc. 4. 
Fig. 2.—Subendothelial intimal proliferation with multinucleated giant cell. The media 
and the adventitia are normal, and the endothelium is intact and unchanged. From Case 
VI. Zeiss, Obj. E, Oc. 4. 
Fig. 3.—Subendothelial proliferation leading to almost complete occlusion of the lumen 
of a medium-sized artery without any changes in the muscular or adventitial layers, the 
endothelial lining being visible, in the centre of the vessel. From Case IX. Zeiss, Obj. 
A, Oc. 4. 
Fig. 4.—Diffuse endarteritis with small intimal tubercle; at a, multinucleated giant 
cell; underneath the tubercle there is perforation of the elastic lamina and beginning 
slight infiltration into the media; otherwise the media and the adventitia are quite un- 
changed. The endothelium, which is present over the diffuse intimal proliferation, is 
absent over the tubercle, which is undergoing caseation and covered with a finely granular 
thrombotic mass. From Case YI. Zeiss, Obj. A, Oc. 2. 
Fig. 6.—Caseous intimal focus which has caused perforation of the elastic layer, the 
ends of which are bent outward, and infiltration into the media and the adventitia, the 
whole having a slight resemblance to a small aneurism. Note the commencing subendo- 
thelial intimal proliferation in the opposite wall of the artery. From Case YII. Zeiss, 
Obj. E, Oc. 2. 
Fig. 6.—Focal tuberculous infiltration with giant cell into and through the wall of a vein 
with secondary thrombosis, the process being due to extension from the neighbourhood. 
Case 11. Zeiss, Obj. C, Oc. 4. 
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FIG. 5. Ludvig Hektoen 
51 
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