into the third, which is characterized by coma, with complete
resolution of the limbs. The constipation frequently gives place to
moderate diarrhœa. The distended fontanel subsides, and often sinks
below the margin of the cranial bones. A striking feature of this
stage is a great increase in the rate of the pulse, the heart being
released from the inhibitory influence of the par vagum in consequence
of the complete paralysis of the latter from pressure. The pulse
varies in rapidity from 120 to 160 or more in the minute. For the same
reason the respiration also {728} increases in frequency, though not
to the same degree. The eyelids are widely open; the pupils are
dilated and generally motionless, even when exposed to a bright light.
The eyes are rolled upward, so that only the lower half of the iris is
visible; the sclerotica is injected from exposure to the air and dust.
Convulsions may occur from time to time. Death terminates the painful
scene, usually in from twenty-four to forty-eight hours, but sometimes
the child lives on for days, unconscious, of course, of suffering,
though the afflicted parents and friends can with difficulty be
brought to believe it.
Certain points in the symptomatology of tubercular meningitis demand
especial consideration.
I have already observed that the division of the disease into definite
stages is purely arbitrary, and is employed here merely for
convenience of description; in fact, few cases pursue the typical
course. A period of active symptoms and another of depression can
often be observed, but these frequently alternate. Stupor and
paralysis may characterize the early stage, and symptoms of
irritation, with restlessness, screaming, and convulsions, predominate
toward the end. Certain characteristic symptoms may be wholly or in
part wanting, such as vomiting, constipation, or stupor.
The temperature shows no changes which are characteristic of the
disease. Throughout its whole course it varies from time to time,
without uniformity, except that it usually rises somewhat toward
night. It seldom exceeds 102° or 103° F., unless shortly before death,
when it may rise to 104° F., or even higher, and may continue to rise
for a short time after death.
During the premonitory stage the pulse offers no unusual
characteristics. Its frequency is often increased, as is usual in any
indisposition during the period of childhood, but it preserves its
regularity. Toward the close of this period, and especially during the
first stage of the disease proper, a remarkable change takes place. It
becomes slow and irregular, the rate often diminishing below that in
health. The irregularity varies in character; sometimes the pulse
intermits, either at regular or irregular intervals. An inequality in
the strength of different pulsations is also observed. These
peculiarities of the circulation are due to the irritation of the
medulla and the roots of the par vagum, by which the inhibitory
function of that nerve upon the action of the heart is augmented.
During the last period, on the other hand, the increasing pressure on
the vagus paralyzes its function, and the heart, freed from its
control, takes on an increased action, the pulse rising to 120 beats,
and often many more, in the minute. Robert Whytt, in his interesting
memoir,[5] dates the beginning of the second stage from the time that
the pulse, being quick but regular, becomes slow and irregular; the
change again to the normal frequency, or beyond it, marking the
commencement of the third stage.
[Footnote 5: “An Account of the Symptoms in the Dropsy of the
Ventricles of the Brain,” in the _Works_ of Robert Whytt, M.D.,
published by his son, Edinb., 1768, p. 729.]
In the early stage the respiration presents nothing abnormal, but when
the pulse becomes slow and irregular the breathing is similarly
affected. Sighing is very common in the prodromal period and first
stage. Toward the end of the second stage the increasing paralysis
{729} of the respiratory centre gives rise to the phenomena known as
the Cheyne-Stokes respiration, consisting of a succession of
respiratory acts diminishing in force until there is a complete
suspension of the breathing, lasting from a quarter to three-quarters
of a minute, when the series begins again with a full inspiration. In
general, the variations in the rate of the respiration follow those of
the pulse, though the correspondence is not always exact.
In the early stage of the disease the pupils are usually contracted
and unequal. They are sluggish, but still respond to the stimulus of
light. At a later period they become gradually dilated, and react even
more slowly to light or not at all, the two eyes often differing in
this respect. Ophthalmoscopic examination frequently shows the
appearance of choked disc and commencing neuro-retinitis. In rare
cases tubercles are seen scattered over the fundus of the eye. They
are about the size of a small pin's head, of a yellowish color, and of
sharply-defined contour. Neuro-retinitis and choked disc are not, of
course, pathognomonic of tubercular meningitis, and choroidal
tubercles are so rarely seen as to be of little avail in diagnosis. In
fact, they are less frequent in this disease than in general
tuberculosis without meningitis. In twenty-six cases of tubercular
meningitis examined by Garlick at the London Hospital for Sick
Children they were found only once.[6] The effect upon the conjunctiva
of the unclosed lids has been already described.
[Footnote 6: W. R. Gowers, M.D., _Manual and Atlas of Medical
Ophthalmoscopy_, Philada., 1882, p. 148. See, also, Seitz, _op. cit._,
p. 347; Steffen, _op. cit._, pp. 452 and 472; and “Tubercle of the
Choroid,” _Med. Times and Gazette_, Oct. 21, 1882, p. 498.]
The tongue is somewhat coated soon after the beginning of the disease,
and the breath is offensive. The appetite is lost, and there is
decided emaciation in many cases during the prodromic period. The
thirst is usually moderate. Vomiting is one of the most constant
symptoms during the first period, and its occurrence on an empty
stomach is characteristic of tubercular meningitis. It is not usually
preceded by nausea, and often takes place without effort, by mere
regurgitation, the rejected fluid consisting chiefly of bile mixed
with mucus. Although constipation is the most common condition in the
early stage, and is often rebellious to treatment, yet in some cases
diarrhœa is observed, which may mislead the physician in respect to
the diagnosis. From the beginning of the second stage, and sometimes
earlier, the discharges from the bowels and the bladder are
involuntary.
DURATION.—The duration of tubercular meningitis, apart from the
prodromic period, which often can hardly be determined, averages from
two weeks to two weeks and a half. In exceptional cases death may take
place in a few days or a week, and occasionally a patient may linger
for several weeks,[7] the difference being apparently due to the
rapidity of the tubercular deposit and of the resulting inflammation
and exudation. The patient usually takes to his bed at the beginning
of the first stage, but he may be up during a part of the day until
the beginning of the second. In rare instances the child will be
about, and even out of doors, until a few days before death.
[Footnote 7: Such a case is reported by Michael Collins in the London
_Lancet_, March 8, 1884.]
PATHOLOGICAL ANATOMY.—The essential lesion of tubercular {730}
meningitis consists in a deposit of miliary tubercles in the pia mater
of the brain, giving rise to inflammation of that membrane and
exudation of serum and pus. In the early stage both surfaces of the
pia are reddened and more or less thickened, and present an opaline
appearance, while between them—that is, in the meshes of the pia—we
find a colorless and transparent fluid which is effused in greater or
smaller amount, resembling jelly when viewed through the arachnoid.
These conditions are sometimes observable on the convexity of the
hemispheres, but are much more abundant on the lateral surfaces, and
especially at the base. More distinct evidence of inflammation is
shown by the presence of a yellowish or greenish-yellow creamy deposit
on the surface of the pia, consisting chiefly of pus, which is also
much more abundant at the base than elsewhere, especially about the
optic commissure, infundibulum, pons Varolii, and the anterior surface
of the medulla. The cranial nerves may be deeply imbedded in the
deposit, which often extends into the fissure of Sylvius, gluing
together the adjacent surfaces of the lobes, and accompanies the
vessels, forming narrow streaks along the sides of the brain up to the
convexity.
The miliary tubercles or granulations consist of semi-transparent
bodies, grayish or whitish in color, varying in size from that of the
head of the smallest pin, indeed almost invisible to the naked eye, to
that of a millet-seed (whence their name). Larger masses are
frequently seen, formed by the aggregation of smaller granulations.
The tubercles are usually found on the inner surface of the pia,
always in the immediate neighborhood of the blood-vessels, which they
accompany in their ramifications, and are also scattered, in greater
or less numbers, throughout the purulent exudation from the surface of
the pia. They are most abundant at the base of the brain, ascending
the sides along the course of the vessels. Sometimes, though rarely,
they are more abundant on the convexity. The total number varies; it
is usually very large, but sometimes only a limited number exists,
even in well-marked cases, and along with intense inflammation of the
pia. The granulations are found in different degrees of
development—sometimes all of them similar in color, size, and
consistency, at others in various stages of fatty degeneration. The
distribution may be symmetrical in the two hemispheres or irregular.
Under the microscope (after suitable preparation of the part) the
bacillus tuberculosus in considerable numbers may be found in the pia,
in places adjacent to the arterioles.[8]
[Footnote 8: See a case reported by Y. Dawson in the London _Lancet_,
April 12, 1884, in which tubercles were visible only by the microscope
with numerous bacilli.]
The ventricles of the brain are usually distended with a clear or
opalescent, rarely bloody, fluid, the amount of which generally
corresponds to the intensity and extent of the meningeal inflammation,
although sometimes it is not above the normal quantity. The two
lateral ventricles are affected in an equal degree; the third and
fourth ventricles are more rarely implicated. According to
Huguenin,[9] it is doubtful whether acute inflammation of the ependyma
takes place in tubercular meningitis. Steffen also[10] says that the
ependyma is not inflamed, and that it is not the seat of the deposit
of tubercles. This latter statement is denied by other authorities,
and Huguenin is inclined to believe that they may exist {731} in that
membrane. In the following case, under my care, abundant granulations
were found on the surface of the ependyma:
[Footnote 9: G. Huguenin, _op. cit._, p. 499.]
[Footnote 10: _Op. cit._, p. 449.]
Olaf M—— (male), æt. 8 years, born in Denmark, entered Massachusetts
General Hospital Sept. 13, 1881. Maternal grandmother died of
consumption; paternal grandfather lived to the age of ninety-five
years. One brother had some disease of hip. Patient was the child of
poor parents and lived in an unhealthy suburb of Boston. During the
two preceding winters he had a bad cough. He was apparently well till
four weeks before his entrance, when he complained of bellyache, and
became listless, but he was out of doors ten days before he came to
the hospital. It was noticed that he was sensitive to sound. No
vomiting, no diarrhœa, no epistaxis, no cry; some cough. He had been
somnolent, and was observed to swing his arm over his head while
asleep. June 14, when first seen by me, he was lying on his back,
unconscious, eyes half closed, pupils dilated, jaw firmly closed, much
emaciated, belly retracted, left leg occasionally flexed and extended.
No priapism. The optic discs were reddened. June 15, there is some
intelligence, he answers questions; keeps one hand on the genitals.
June 16, pupils contracted, does not swallow. June 18, left eye
divergent, conjunctiva injected, whole surface livid, cries out
occasionally. Died at midnight.
[Illustration: FIG. 30. Temperature chart of a case of tubercular
meningitis in a boy eight years old.]
Autopsy.—General lividity of surface, much emaciation. Much fine
arborescent injection on outer surface of dura mater. Numerous
Pacchionian bodies. Yellow matter beneath arachnoid along course of
vessels on each side of anterior lobes. Abundant fine granulations
along course of vessels on each anterior lobe, on upper margins of
median fissure, along fissure of Sylvius, and on choroid plexuses.
Very little lymph at base of brain. Six or eight ounces of serum from
lateral ventricles, and abundant fine transparent granules over
ependyma of both. Numerous opaque granulations in pia mater of medulla
oblongata. Surface of right pleura universally adherent. Mucous
membrane of bronchia much injected; a considerable amount of pus
flowed from each primary bronchus. No tubercles in lungs nor in
peritoneum. No ulcerations in intestines. No other lesions.
The choroid plexuses are generally involved in the inflammatory
process, and are sometimes covered with yellow purulent exudations. As
in the above case, large numbers of tubercles may be found in them,
notwithstanding the opinion of Huguenin that their number is always
small.
The substance of the brain in the vicinity of the tubercular deposit
is generally found in a more or less œdematous condition, owing to the
obstruction of the circulation resulting from compression of the
vessels {732} by the tubercles and effused lymph. Softening, sometimes
even to diffluence, not unfrequently occurs in the neighborhood of the
deposit, probably from ischæmia (necrobiosis). If there be any
considerable amount of exudation in the ventricles, the convolutions
are flattened by compression against the cranial bones.
The above-described lesions are not confined to the brain, but may
extend to the cerebellum, the pons, the medulla, and the spinal cord.
If examinations of the latter were more frequent in autopsies of this
disease, we should doubtless find, as has been done in some instances,
that the membranes often show the characteristic alterations of
tubercular meningitis, and even the presence of granulations in the
cord itself. The lesions may extend throughout the cord, and are
especially noticed in the dorsal region and in the vicinity of the
cauda equina. Their presence explains some of the symptoms evidently
due to spinal origin, such as retraction of the head with rigidity of
the neck and of the trunk, contractions of the limbs, tetanic spasms,
priapism, paralysis of the bladder and rectum, etc., which are common
in simple spinal meningitis.
The deposit of miliary tubercles in the pia mater, with little or no
accompanying meningitis, is met with in rare instances. The tubercles
are few in number, but vary in dimensions, being sometimes united
together in masses of considerable size, which are frequently
encysted. Beyond thickening and opacity of the membrane, their
presence seems to excite but little inflammatory reaction, but they
are generally accompanied by ventricular effusion which by its
pressure gives rise to characteristic symptoms.
The principal lesions found in other organs of the body consist of
tubercle in various stages of development, caseous matter, diseases of
the bones, etc. Miliary granulations are chiefly seen in the lungs,
peritoneum, intestinal mucous membrane, pleura, spleen, liver, and
kidneys. The bronchial and mesenteric glands often contain caseous
masses, some of which are broken down and suppurating. The testicles
sometimes present the same appearances. In adults, the most frequent
lesion which is found external to the brain is pulmonary tuberculosis
in a more or less advanced stage. Tubercles are also sometimes present
in the eye. Angel Money[11] states that out of 44 examinations made at
the Hospital for Sick Children, London, the meninges were the seat of
gray granulations in 42. The choroid (one or both) showed tubercles 14
times (right 3, left 5, both 6), and 11 times there were undoubted
evidences of optic neuritis. Twice the choroid was affected with
tubercle when the meninges were free; in one of these instances there
was a mass of crude tubercle in the cerebellum; in the other, although
there were tubercles in the belly and chest, there were none in the
head. So that 12 times in 42 cases of tubercles in the meninges there
were tubercles in the choroid—_i.e._ about 31 per cent.
[Footnote 11: “On the Frequent Association of Choroidal and Meningeal
Tubercle,” _Lancet_, Nov. 10, 1883.]
DIAGNOSIS.—In many cases tubercular meningitis offers but little
difficulty in the diagnosis. Although the symptoms, taken singly, are
not pathognomonic, yet their combination and succession, together with
their relation to the age, previous health, and antecedents of the
patient, are usually sufficient to lead us to a correct opinion. The
prodromic period {733} of altered disposition (irritability of temper
or apathetic indifference), headache, constipation, vomiting, and
emaciation, followed by irregularity and slowness of the pulse,
sighing respiration, sluggishness and irregularity of the pupils; the
progress from somnolence to unconsciousness and coma; the sudden
lamentable cry; the convulsions and paralysis; the return of rapid
pulse and respiration in the last stage,—are characteristic of no
other disease. Our chief embarrassment arises during the insidious
approach of the malady, before its distinctive features are visible or
when some important symptom is absent. Its real nature is then apt to
be overlooked, and, in fact, in some cases it is impossible to decide
whether the symptoms are indicative of commencing cerebral disease,
or, on the other hand, are owing to typhoid fever, to a simple
gastro-intestinal irritation from error in diet, to worms in the
alimentary canal, to overwork in school, or to some other cause. Under
these circumstances the physician should decline giving a positive
opinion until more definite signs make their appearance. It must be
remembered that very important symptoms may be absent in cases which
are otherwise well marked. In all doubtful cases the family history
should, if possible, be obtained, especially whether one or both
parents or other near relatives have been consumptive or have shown
symptoms of scrofula or tuberculosis in any form, and whether the
patient himself has signs of pulmonary tuberculosis, of enlarged or
suppurating glands, or obstinate skin eruptions. The presence or
history of those conditions would add greatly to the probability of
tubercular meningitis.
The diseases for which tubercular meningitis is most liable to be
mistaken are acute simple meningitis, typhoid fever, acute
gastro-intestinal affections, eclampsia of infants and children, worms
in the intestines or stomach, the hydrencephaloid disease of Marshall
Hall, and cerebro-spinal meningitis.
Acute meningitis is distinguished from the tubercular disease by its
sudden invasion without prodromatous stage, by the acuteness and
intensity of the symptoms, the severity of the headache, the activity
of the delirium, the greater elevation of the temperature, and by its
brief duration, which rarely exceeds one week. In those exceptional
cases of tubercular meningitis in which the prodromal period is absent
or not observed and the course is unusually rapid, it would be perhaps
impossible to distinguish between the two diseases. A family history
of tubercle, or the discovery of the granulations in the choroid by
ophthalmoscopic examination, might save us from error under such
circumstances. The great rarity of idiopathic simple meningitis should
be remembered. Meningitis from disease of the ear sometimes resembles
the tubercular affection, but the history of the attack, usually
beginning with local pain and otorrhœa, will in most cases prevent any
confusion between the two forms of disease.
The early period of typhoid often bears considerable resemblance to
that of tubercular meningitis. Headache, languor, restlessness, and
mild delirium are common to both. Typhoid can be distinguished by the
coated tongue, the diarrhœa, the enlargement of the spleen, the
tympanites, abdominal tenderness and gurgling, the eruption, and,
above all, by the characteristic temperature-curve, which, if
accurately observed, is conclusive. The course of typhoid fever is
comparatively {734} uniform, while that of tubercular meningitis is
often extremely irregular. It should not be forgotten that the two
diseases may coexist.
The presence of worms in the alimentary canal may cause symptoms
somewhat like those of tubercular meningitis, and the symptoms of the
latter disease are occasionally erroneously attributed to those
parasites. The administration of an anthelmintic, which should never
be omitted in doubtful cases, will clear up all uncertainty.
Cerebro-spinal meningitis is usually an epidemic, and therefore not
likely to be confounded with the tubercular disease. In sporadic cases
it can be recognized by its sudden onset and acute character, by the
eruption, and by the prominence of the spinal symptoms.
The so-called hydrencephaloid disease of Marshall Hall is a condition
of exhaustion and marasmus belonging to infancy, caused by
insufficient or unsuitable nourishment, by diarrhœa, and by the
injudicious depletive treatment so much in vogue in former times, when
the affection was much more common than at present. Some of its
symptoms, such as sighing respiration, stupor, pallor, and dilated
pupils, bear a certain resemblance to those of tubercular meningitis,
though it would be more easily confounded with chronic hydrocephalus.
The absence of constipation, headache, convulsions, and vomiting, and
the favorable results of suitable nourishment and stimulants, serve to
distinguish it from cerebral disease.
Eclampsia, or sudden convulsion, is common in infants and young
children, and, since the occurrence of a fit may be the first or the
most striking symptom in tubercular meningitis, it is important to
ascertain its origin. In the majority of cases convulsions in children
arise from some peripheral irritation, such as difficult dentition,
worms in the alimentary canal, constipation, fright, etc., acting
through the reflex function of the spinal cord, which is unusually
sensitive in the early period of life. The absence of previous
symptoms, and the discovery of the source of the irritation, with the
favorable effect of its removal by appropriate treatment, will in most
cases suffice to eliminate structural disease of the brain. In others
we must withhold a positive opinion for a reasonable time in order to
ascertain whether more definite symptoms follow. Convulsions also
occasionally form the initial symptom of the eruptive fevers,
especially scarlatina. Here the absence of prodromal symptoms, and the
speedy appearance of those belonging to the exanthematous affection,
will remove all sources of doubt. Convulsions, with or without coma,
occurring in the early stage of acute renal inflammations, may
simulate the symptoms of tubercular meningitis. An examination of the
urine will show the true nature of the disease.
In addition to the above diseases there are some cerebral affections
of uncertain pathology which resemble tubercular meningitis, but which
are not generally fatal. As Gee justly remarks,[12] “Every
practitioner from time to time will come across an acute febrile
disease accompanied by symptoms which seem to point unmistakably to
some affection of the brain, there being every reason to exclude the
notion of suppressed exanthemata or analogous disorders. After one or
several weeks of coma, delirium, severe headache, or whatever may have
been the prominent symptom, the patient recovers, and we are left
quite unable to say what has been the {735} matter with him. To go
more into detail, I could not do otherwise than narrate a series of
cases which would differ from each other in most important points, and
have nothing in common excepting pyrexia and brain symptoms. There is,
generally, something wanting which makes us suspect that we have not
to do with tubercular meningitis. Brain fever is as good a name as any
whereby to designate these different anomalies; cerebral congestion,
which is more commonly used, involves an explanation which is probably
often wrong, and certainly never proved to be right.” No doubt such
cases are occasionally cited as examples of recovery from tubercular
meningitis.