546 THE CANADIAN MEDICAL ASSOCIATION JOURNAL
SEROUS MENINGITIS
BY GEORGE F. BOYER, M.D.
Toronto
THE diagnosis of serous meningitis is one that
is made sufficiently often to justify some
discussion of its merit, and an examination of
the conditions that enter into its etiology. The
term "meningism" is constantly coupled with
that of "serous meningitis," and unless this
condition is identified definitely and absolutely
with a cerebro-spinal fluid normal in appear-
ance, cytology and chemistry, we are at the start
confused in the use of two different terms.
Therefore, at the outset, in the course of these
remarks, meningism will be characterized by a
cerebro-spinal fluid normal in all points except
that of increased pressure. This term was in-
troduced by Dupre in 1894, and has been re-
sponsible for some confusion since, for some
authorities still assert that "in some instances
there may be twenty, thirty, or even more cells,
but the fluid is clear, and no organisms are
found." If this definition is accepted, we can-
not differentiate serous meningitis from it. A
"meningism" is properly the state in which a
patient presents clinically the symptoms and
signs of meningeal irritation, of variable in-
tensity but in reality benign; and, on lumbar
puncture, the cerebro-spinal fluid is found to be
practically normal. Serous meningitis, on the
other hand, has been associated with four dif-
ferent groups, or stages, of somewhat similar
findings, but all of these manifest more or less
distinctive changes in the cerebro-spinal fluid.
This condition is identified with infection, tox-
aemia, or direct irritation after the intrathecal
injection of sera, and such like. These result
in a change in the secretion and absorption (one
or both), local or general, of the cerebro-spinal
fluid.
For the sake of classification, serous menin-
gitis may be grouped under the following
headings:-
1. The usual acute form, associated with
alcoholism, anaemia, etc., and characterized by
signs of coma and the cerebro-spinal fluid
changes, of increased pressure, and increased
globuliln, but without change in the cytology or
sugar-content. This is an uncommon condition
in children and will be passed over at present.
2. The form of serous ineningitis which is
associated with the infectious fevers, and most
typically seen with, or just following, measles,
and usually presents changes in the pressure,
cytology, and chemistry of the cerebro-spinal
fluid.
3. Meningitis sympathetica. This is the form
of serous mening(fitis that is of most interest to
us to-day, as a clinical problem. In its true
form it is but a defence phenomenon, and
should be associated in one 's mind with
acute infection, with or without suppuration in
the upper respiratory passages or their acces-
sory sinuses; or it might result from the menin-
geal reactions around adenitis, deep cellulitis.
thrombophlebitis outside the cranial cavity,
or even brain-abscess. This condition is charac-
terized clinically by symptoms and signs of
meningitis; the cerebro-spinal fluid showing an
increase in amount and in pressure, a slightly
granular appearance, an increase in globulin
content, an increase in cells (either lymphocytes
or polymorphonuclears, or both), and a fluid
which is culturally sterile.
4. Aseptic meningitis. This form is but the
meningeal reaction which may result from the
injection of sterile foreign substances (usually
sera) into the subarachnoid space. Even
stovaine is credited with producing this re-
action. The cerebro-spinal fluid may be under
great increase in tension, may be opalescent, or
frankly purulent with marked cell changes,
with polymorphonuclear cells predominating.
Globulin is increased, but the sugar-reaction is
ifot changed, and the fluid shows no signs of
bacteria, either by smear or culture.
For the purpose of this paper, consideration
will be given chiefly to that type of serous
meningitis termed sympathetic meningitis, and
my remarlks will be limited mainly to a con-
sideration of the changes in the cerebro-spinal
fluid and their possible explanation. Before
doing this, however, it might be wise to diaress
 BOYER: SEROUS MENINGITIS 541
-~
sufficiently long to consider briefly such impor- ventricles, cisternae, and lumbar sac, i.e., the
tanit points as the origin, circulation, and ab- height of the fluid columns in the manometers is
sorption of this fluid, the evidence available on the same horizontal plane; the fluids are
to-day suggesting that it varies in its normal uniformly clear and colourless and do not clot;
and abnormal characteristics at different places and cells are absent in the ventricle, although
in the same cerebro-spinal system, in the frequently a few are found in cisternal and
cytology of the normal cerebro-spinal fluid, and lumbar fluids, under what must be considered
paths of possible infection. normal conditions. The Wassermann and
It is somewhat generally accepted to-day that colloidal tests, gold chloride, benzoin, and
the cerebro-spinal fluid is the secretion of the mastic, are uniformly negative.
choroid plexus of the lateral and fourth "While globulin (ammonium sulphate ring
ventricles. With this, there is probably some test) is normally absent in all three fluids,
small part of the fluid derived from the peri- slight but constant differences are seen in the
cellilar spaces, both of which directly com- total protein-content, as indicated by tri-
municate with the subarachnoid space. The chloracetic acid and sulphosalicylic acid tests,
flow of cerebro-spinal fluid is from the peri- the greatest amount appearing in lumbar, less
cellular and perivascular spaces into the sub- in cisternal, and the least in ventricular fluids.
arachnoid space. The circulation of the While the normal figures vary, 30 mgm. per
cerebro-spinal fluid, after it has escaped from 100 c.c. in lumbar, 25 in cisternal, and 10 in
the ventricular system, is not well known. It ventricular fluids, would be considered as the
is probably renewed in its entirety every four normal ratio. Conspicuous is the opposite
hours, and this means a daily secretion of from iatio in regard to sugar-content. Sugar is
six to seven hundred cubic centimetres. In TABLE I
1919, Dandy placed indian ink in the ventricles; COMPARATIVE FLUID EXAMINATIONS FROM VENTRICLE
AND LUMBAR SAC IN CASES OF GENERAL PARESIS*
it first filtered into the cisterna; then the sub-
arachnoid spaces of the cerebellum filled, and Wassermann Total
reaotion Cells Globulin protein
the fluid spread outward anld upward into C. M.
the sulci of the hemispheres. In forty-five to Lumbar Pos. 0.05 c.c. 45 + ++
Ventricle Neg. 1.0 c.c. 30 0 Normal
seventy-five minutes it reached the more remote Lumbar Pos. 0.05 c.c. 14 ++ ++
parts of the longitudinal sinus. Phenolsulphon- Ventricle Neg. 1.0 c.e. 2 + +
ephthalein is absorbed and excreted much faster Lumbar Pos. 0.05 c.c. 10 + +
Ventricle Neg. 1.0 c.c. 6 0 Normal
than this, so it may not be that the only main S. G.
channel of absorption is through the arach- Lumbar Pos. 0.8 c.c. 2 + +
Ventricle Neg. 1.0 c.c. 2 0 Normal
noidal villi into the large venous channels, as R. C.
is the accepted teaching to-day. It may be Lumbar Pos. 0.05 c.c.
that a great deal of absorption of the cerebro- Ventricle Pos. 0.8 c.c. .
A. G.
spinal fluid takes place in the tissue of the Lumbar Pos. 0.2 c.c. 2 ++ +
perivascular spaces. There are also significant Ventricle Neg. 1.0 c.c. 0 0 Normal
data pointing to there being some downward A. F.
Lumbar Pos. 0.3 c.c. 0 ++ +
circulation of the cerebro-spinal fluid in the Ventricle Pos. 0.3 c.c. 1 + +
spinal canal, for, in 1921, Weigeldt found in Lumbar Poe. 0.1 c.c. 5 +-+j+ ++
many fluids examined that albumin and cells
Ventricle Pos. 0.1 c.c. 3 + +-
Lumbar Pos. 0.3 c.c. 6 ++ ++
progressively increased from the cervical to the Ventricle Pos. 0.3 c.c. 0 - +
lumbar region. It is also well established that H. P.
Lumbar Pos. 0.6 c.c. 15 ++ +++
the ventricular fluid may be colourless and the Ventricle Neg. 1.0 c.c. 2 + +
spinal fluid bile-stained in icterus; in paresis Lumbar Pos. 0.2 c.c. 27 ++ ++
Ventricle Neg. 1.0 c.c. 7 + Normal
negative Wassermann reactions have been ob- Lumbar Pos. 0.2 c.c. 39 +++ +++
tained in the ventricular fluid and positive re- Ventricle Neg. 1.0 c.c. 0 + +
actions in the spinal fluid in the same group of Lumbar Pos. 0.2 c.c. 32 ++++ +++
Ventricle Neg. 1.0 c.c. 2 0 Normal
cases. Ayer and Solomon (The Human Cerebro- Lumbar Positive 13 ++ +++
Cistern Positive 18 ++ +++
Spinal Fluid) state that, in normal cerebro-
spinal fluid, the pressure is similar in the *
Table from The Hluman Cerebro-Spinal Fluid.
548 THE CANADIAN MEDICAL ASSOCIATION JOURNAL
greatest in amount in the ventricular fluid
(approximately .08 per cent) and least in the
lumbar sac (averaging about .06 per cent), the
cisternal fluid showing a value between these
two."
The table below shows in a convenient form,
in connection with a well-defined pathological
state, figures for certain of the features re-
ferred to, compared according to location.
It is thus evident that increase of cells and
globulin is more characteristic of extra-
ventricular fluid, that is, the only really normal
cerebro-spinal fluid is that found near its
source. namely, in the ventricles. The number
of cells in normal cerebro-spinal fluid is
variously given by different authorities. Levin-
son gives four to six cells per cubic millimeter.
all being small lymphocytes. Fontecilla and
Sepulveda, and several other authorities, state
that normal fluid contains few if any cells, and
put one per cubic millimeter as the maximum.
and consider that more than one is indicative of
inflammatory reactions. The origin of these
cells, under normal conditions, is not known. It
is thought that they wander from the blood and
pass through the walls of the choroid plexus.
But that is not the only source, for in ap-
parently healthy fluids more cells are found in
the cisternw and lumbar sac than in the ven-
trieles. Under abnormal conditions, however,
there is no doubt that cells come directly from
the vessels into the perivascular spaces, as seen
in encephalitis, poliomyelitis, tetanus, etc.
Another very significant portal of entry for
irritative substances is through the perineural
lymphaties of the afferent and efferent cerebral
and spinal nerves.
Orr and Rows (Brain, xxxvi, 271), in an ex-
haustive paper, conelude that: "The precise
origin of the cells composing an inflammatory
reaction is always a matter of great difficulty,
and some points must remain obscure, but a
consideration of the mechanism by which the
inflammation is produced should prove of very
great assistance, especially in the case of
lymphogenous infections. In experimental
lymphogenous infection of the spinal cord of a
subacute nature, in which all the inflammatory
phenomena are extravascular, and the path of
the toxic lymph can be traced accurately, we
find that besides the proliferation of the con-
nective tissue in the meninges the only strue-
tures which react are the adventitial cells of the
veins and capillaries and the neuroglia cells im-
mediately in contact with them. The adventitia
takes an extremely important part in the pro-
duction of the cells of reaction; this is not sur-
prising, seeing that the cerebro-spinal lymph
flows directly into its spaces. Hence, when a
toxin gains the central nervous system by the
lymph path the cells of the adventitial sheath
are the part of the vessel to be first attacked;
and should the irritant be weak or permeate the
tissues slowly no other phenomena need occur
for some time. In more acute conditions, how-
ever, not only is there a more intense reaction
in the tissues already mentioned, but the en-
dothelial cells join in the process; and with a
still greater degree of potency in the infection,
intravascular chag(es, such as hwmorrhage and
thrombosis, complicate the picture."
In serous meningitis, as in many forms of
meningitis, it is not definitely known by what
route infection gains access to the central nerv-
ous system. If the infection is central and be-
comes free in the cerebro-spinal fluid, we no
longer are dealing with serous meningitis.
Conditions have advanced past a defensive
phenomenon which might be comparable with a
sterile serous effusion ilnto the synovial sac of
the knee in the presence of a general or local
infection in a lower limb.
A point to stress is that in the clinical con-
dition knowvn as serous meningitis, the outloolW
and the sequelae are much more favourable than
the onset of clinical signs and the cerebro-
spilnal fluid findings would lead one to suppose.
We do not know whether these toxins (or in-
fections) reach the central nervous system by
the lymphaties, the perineural spaces, or the
blood vessels. It is possible that the toxin (or
infection) may become centralized by way of
these routes, and when an acute clinical
meningitis, amicrobic by direct smear and by
culture, occurs concurrently with an acute
febrile state (especially with infection in the
upper respiratory tract, ears, sinuses, etc.) we
may be dealing solely with a normal defence
reaction of the meninges, which does not
necessarily constitute a basis for serious appre-
hension. Many clinical conditions are known
to give rise to cytological and chemical changes
in the cerebro-spinal fluid. From this general
group bacteriological examination often proves
 BOYER: SEROUS AIENINGITIS 549
-~~~~~~~BYR SEOSMNNII

definitely a known infection. In a large gested, and there was a slight cervical adenitis. Kernig
and Brudzinski signs were positive. The child was
number the clinical history and concurrent irritable and hypersensitive to examination. The optic
systemic symptoms and signs point the way to discs were normal.
Cerebro-spinal fluid, 10 a.m. (before admission);
a differential diagnosis in a definite proportion, pressure +; just cloudy; 1000 cells per e.mm.; globulin
as in poliomyelitis, tetanus, tuberculosis, etc., +; polymorphunclear cells, 76 per cent, lymphoeytes 24
per cent. A few hours later: pressure +; faintly
and, for the remainder, we are still left with cloudy; 650 cells; globulin +; polymorphonuelears 82
the diagnosis of a condition for which we use per cent, lymphocytes 18 per cent. Forty e.e. of anti-
the term "serous meningitis." Table II gives meningoeoccic serum were given intravenously; smear,
negative; urine, normal.
an analysis, from the present standpoint, of December 20th. Temperature 101.40; pulse 130;
twenty-four cases of serous meningitis of which respiration 32. He vomited immediately after taking
food; was' less irritable; slept more. The ear drums
I have notes. were dull in appearance; cervical adenitis was present.
Cerebro-spinal fluid: pressure +; faintly cloudy; 750
TABLE II cells; globulin +; polymorphonuelears 75 per cent;
SEROUS MENINGITIS-24 CASES lymphocytes 25 per cent. Twenty e.e. of antimeningo-
Age: 12 were 5 years or under coccic serum were given intraspinously. Tuberculin tests
9 were 6 years to 10 years were negative; smears, negative; cultures, sterile.
3 were over 10 years. December 21st. Temperature 101.4; pulse 148;
Sex: 20 malesL--4 females. respiration 36. WVhite blood cells, 7600; 76 per cent
Area of infection: polymorphonuelears; 24 per cent lymphocytes. Head
Otitis media .12 retraction; general improvement. Cultures were sterile.
Pharyngitis .6 December 22nd. Temperature 1000; pulse 100; res-
Tonsillitis. 5 piration 28. Improving generally. Twenty c.c. of anti-
Adenitis. 2 meningitic serum given intraspinously. Cerebro-spinal
Rhinitis. 1 fluid: pressure +; very faintly cloudy; 155 cells;
Fractured skull. 5 globulin +; polymorphonuelears 52 per cent; lym-
Bronchopneumonia. 3 phoeytes 48 per cent.
Septiewmia. 2 Detember 23rd. Temperature 1000; pulse 118; res-
Cellulitis of cheek. 1 piration 28. White blood cells, 7400, 56 per cent poly-
Season: morphonuelears, 44 per cent lymphoeytes; resting more
Winter. 5 quietly; rigidity of neck still; also marked Kernig sign.
Spring. 8 December 25th. Temperature 100.40; pulse 116;
Summer. 7 respiration 24; improving; cultures sterile. (cerebro-
Autumn. 4 spinal fluid and blood).
Results: December 27th. Temperature 102.40; pulse 128;
Cured .13 respiration 32. Much more irritable; head retraction,
Improved. 3 and Kernig marked. Cervical adenitis, especially left
Died .6 side marked. Ear drums "dull."
From septicaemia. 2 December 28th. Temperature 100.40; pulse 110;
Otitis media and bronchopneumonia 2 respiration 28; definite adenitis, especially of the
Otitis media, rickets, decomposition 1 posterior chain oln the left side. Discs normal. General
Otitis media (died soon after admis- condition more satisfactory.
sion; no lumbar puncture re- Decemnber 30th. Temperature 99.20; pulse 108;
ported) .................... 1 respiration 28; discharged to go home. General condi-
C. S. fluid findings: tion fair. Local condition in ears doubtful, but deep
Highest cell count, 7000. glands of the neck, especially below the left mnastoid
Lowest cell count, 11 per c.mm. and the posterior chain, very definitely enlarged; these
Average cell count in 21 cases: were opened about one week later (streptococcus hemo-
778 cells per c.mm. lyticus recovered in pure culture). A deep cellulitis
Lymphocytes predominated in 70.6 per cent of developed, and later erysipelas to clavicles.
cases. January 1, 1922. Transfused. After this he de-
Polymorphonuclear leucocytes predominated in veloped an acute otitis media in one ear; in 24 hours
29. 4 per cent of cases. he developed it in the other ear (both opeiled). From
then on he has made a slow but good recovery. He has
The following is a typical example of the remained well since.
affection:- I have intentionally evaded anly detailed
Case D.A.H. AMale, aged 5 years; admitted to hos,- enumeration of clinical symptoms and signs,
pital December 19, 1921. but have preferred rather to leave these in the
Family history: excellent. Previous history: chicken-
abstract by the use of the term "meningeal
pox, 1917; measles, 1919; appendicitis, 1920; tonsillitis,
recurring attacks.
Present illness: six days ago he had a head-cold. irritation," and to devote this brief discussion
Five days ago he had earache for one night. One ear to the points of greatest diagnostic importance,
was congested. Eighteen hours ago frontal and occipital
headache began. Temperature 99.60. A very restless
namely, the relationship to the primary focus
night followed; pain in the back was complained of and and the differential diagnosis after careful de-
he said it hurt his head to sit up. Slight twitching of tailed examination of the cerebro-spinal fluid.
arms and legs was noticed.
Condition on adminssion: December 19, 1921. Tem- My remarks as to treatment are very brief, for
perature 106.80; pulse-140; respiration 28. White blood 1 feel that only two methods are worthy of con-
eells, 9200; 86 per cent were polymorphonuelear. The sideration, namely, efforts to relieve the general
ears appeared normal; the tonsils were slightly con-
550 THE CANADIAN MEDICAL ASSOCIATION JOURNAL
or local causative condition, and, secondarily,
the probable efficacy of repeated lumbar punc-
ture for the purpose of drainage. This latter
procedure is not without possible danger, how-
IDIOPATHIC HAMORRHAGE OF THE NEW-BORN*
BY JAMES L. MCCOLLUM
Toronto
VHAT is the cause of " idiopathic hawmor-
hage of the new-born?" Is it due to an
infection? Is it brought about by the lack of
certain constituents of the blood? Is it caused
by a temporary deficiency of vitamine B in the
blood of the infant? Or, shall we ever know
the underlying etiological factors of this dis-
ease ?
Idiopathic hamorrhage of the new-born is a
term used to designate a condition or disease in
infants which manifests itself shortly after birth
by spontaneous bleeding, and in which no birth.
injury, other trauma, or other forms of disease
have acted as causative factors.
We can conveniently divide all cases of hoe-
morrhage of the new-born into two groups:-
1. Priminary, (also called "idiopathic.")
2. Secondary, associated with-
(a) Trauma.
(b) Infections.
(3) Syphilis.
In this paper it is the primary variety that I
wish to discuss, as "haemorrhage of the new-
born" in toto is by far too extensive a subject
for the allotted time.
PATHOLOGY
Unfortunately the pathology throws but little
light on the subject. All that we can find is
h'wmorrhage, and, from autopsies we can do little
more than classify the areas or organs showing
the presence of blood, and find the parts most
often affected.
Hamorrhagic areas may be found in the
mucous membrane of the stomach and of the
intestine; ecchymoses may be found in the skin,
*From the Sub-department of Pediatrics of the
University of Toronto, and the wards of the Hospital
for Sick Children under the direction of Alan Brown.
Read at the Pediatric Reading Club, January 120.
1928.
ever, for it is reasonable to expect that too
frequent, or too complete, drainage might tend
to spread an otherwise localizing meningeal
condition.
often diffuse; signs of bleeding may be also
discovered in the pericardium, peritoneum, in
the serosa of the lungs, and in any of the in-
ternal organs. Intracranial hwmorrhage is
usually subdural and may cover any part of
the brain or extend into the spinal cord. Moyni-
han points out a very definite relationship be-
tween duodenal ulcer and melwna neonatorum,
and found ulcers in sixteen tvpical cases of this
disease. Infection, necrosis, and thrombosis of
the small vessels in the duodenal wall are given
as causes for these ulcers. However, as melawna
neonatorum usually shows a rapid and unevent-
ful convalescence, it is hard to conceive that
many cases have definite duodenal ulcer, or that
the ulcer is similar to that found in the duo-
denum of the adult. When extensive hawmor-
rhage occurs intracranially most pathologists
consider this to be the direct cause of death;
and Green states that extensive subdural bleed-
ing may occur, either from trauma alone, or in
association with hwmorrhage of the new-born.
OCCURRENCE AND DIAGNOSIS
Morbus hemorrhagica neonatorum is a rare
disease, occurring in about 1 per cent of all
births. The idiopathic variety is, of course,
even rarer. Townsend3 judges it to be about one-
quarter of one per cent, and states that he has
found it to be more common in institutions than
in private practice. Many observers state that
the incidence of the disease increases when
epidemics of sepsis occur in hospitals, but Holt
has investigated this question carefully, and
declares that he has found no increase among
the cases of primary hamorrhage under such
circumstances.
The clinical picture of this disease is definite
and easy to recognize. Medical advice is usually
sought very early for the child in this condition,