546 THE CANADIAN MEDICAL ASSOCIATION JOURNAL

SEROUS BY GEORGE F. BOYER, M.D. Toronto THE diagnosis of serous meningitis is one that sugar-content. This is an uncommon condition is made sufficiently often to justify some in children and will be passed over at present. discussion of its merit, and an examination of 2. The form of serous ineningitis which is the conditions that enter into its etiology. The associated with the infectious , and most term "meningism" is constantly coupled with typically seen with, or just following, , that of "serous meningitis," and unless this and usually presents changes in the pressure, condition is identified definitely and absolutely cytology, and chemistry of the cerebro-spinal with a cerebro-spinal fluid normal in appear- fluid. ance, cytology and chemistry, we are at the start 3. Meningitis sympathetica. This is the form confused in the use of two different terms. of serous mening(fitis that is of most interest to Therefore, at the outset, in the course of these us to-day, as a clinical problem. In its true remarks, meningism will be characterized by a form it is but a defence phenomenon, and cerebro-spinal fluid normal in all points except should be associated in one 's mind with that of increased pressure. This term was in- acute , with or without suppuration in troduced by Dupre in 1894, and has been re- the upper respiratory passages or their acces- sponsible for some confusion since, for some sory sinuses; or it might result from the menin- authorities still assert that "in some instances geal reactions around adenitis, deep cellulitis. there may be twenty, thirty, or even more cells, thrombophlebitis outside the cranial cavity, but the fluid is clear, and no organisms are or even brain-abscess. This condition is charac- found." If this definition is accepted, we can- terized clinically by symptoms and signs of not differentiate serous meningitis from it. A meningitis; the cerebro-spinal fluid showing an "meningism" is properly the state in which a increase in amount and in pressure, a slightly patient presents clinically the symptoms and granular appearance, an increase in globulin signs of meningeal irritation, of variable in- content, an increase in cells (either lymphocytes tensity but in reality benign; and, on lumbar or polymorphonuclears, or both), and a fluid puncture, the cerebro-spinal fluid is found to be which is culturally sterile. practically normal. Serous meningitis, on the 4. Aseptic meningitis. This form is but the other hand, has been associated with four dif- meningeal reaction which may result from the ferent groups, or stages, of somewhat similar injection of sterile foreign substances (usually findings, but all of these manifest more or less sera) into the subarachnoid space. Even distinctive changes in the cerebro-spinal fluid. stovaine is credited with producing this re- This condition is identified with infection, tox- action. The cerebro-spinal fluid may be under aemia, or direct irritation after the intrathecal great increase in tension, may be opalescent, or injection of sera, and such like. These result frankly purulent with marked cell changes, in a change in the secretion and absorption (one with polymorphonuclear cells predominating. or both), local or general, of the cerebro-spinal Globulin is increased, but the sugar-reaction is fluid. ifot changed, and the fluid shows no signs of For the sake of classification, serous menin- bacteria, either by smear or culture. gitis may be grouped under the following For the purpose of this paper, consideration headings:- will be given chiefly to that type of serous 1. The usual acute form, associated with meningitis termed sympathetic meningitis, and alcoholism, anaemia, etc., and characterized by my remarlks will be limited mainly to a con- signs of coma and the cerebro-spinal fluid sideration of the changes in the cerebro-spinal changes, of increased pressure, and increased fluid and their possible explanation. Before globuliln, but without change in the cytology or 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 it first filtered into the cisterna; then the sub- AND LUMBAR SAC IN CASES OF GENERAL PARESIS* 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 + + Lumbar Pos. 0.05 c.c. 10 + + ephthalein is absorbed and excreted much faster 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 villi into the large venous channels, as noidal 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+ + + Ventricle Pos. 0.1 c.c. 3 + +- many fluids examined that albumin and cells 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 + + Lumbar Pos. 0.2 c.c. 32 ++++ +++ actions in the spinal fluid in the same group of Ventricle Neg. 1.0 c.c. 2 0 Normal cases. Ayer and Solomon (The Human Cerebro- Lumbar Positive 13 + + + + + Spinal Fluid) state that, in normal cerebro- Cistern Positive 18 + + +++ 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 tures which react are the adventitial cells of the (approximately .08 per cent) and least in the veins and capillaries and the neuroglia cells im- lumbar sac (averaging about .06 per cent), the mediately in contact with them. The adventitia cisternal fluid showing a value between these takes an extremely important part in the pro- two." duction of the cells of reaction; this is not sur- The table below shows in a convenient form, prising, seeing that the cerebro-spinal lymph in connection with a well-defined pathological flows directly into its spaces. Hence, when a state, figures for certain of the features re- toxin gains the central nervous system by the ferred to, compared according to location. lymph path the cells of the adventitial sheath It is thus evident that increase of cells and are the part of the vessel to be first attacked; globulin is more characteristic of extra- and should the irritant be weak or permeate the ventricular fluid, that is, the only really normal tissues slowly no other phenomena need occur cerebro-spinal fluid is that found near its for some time. In more acute conditions, how- source. namely, in the ventricles. The number ever, not only is there a more intense reaction of cells in normal cerebro-spinal fluid is in the tissues already mentioned, but the en- variously given by different authorities. Levin- dothelial cells join in the process; and with a son gives four to six cells per cubic millimeter. still greater degree of potency in the infection, all being small lymphocytes. Fontecilla and intravascular chag(es, such as hwmorrhage and Sepulveda, and several other authorities, state thrombosis, complicate the picture." that normal fluid contains few if any cells, and In serous meningitis, as in many forms of put one per cubic millimeter as the maximum. meningitis, it is not definitely known by what and consider that more than one is indicative of route infection gains access to the central nerv- inflammatory reactions. The origin of these ous system. If the infection is central and be- cells, under normal conditions, is not known. It comes free in the cerebro-spinal fluid, we no is thought that they wander from the blood and longer are dealing with serous meningitis. pass through the walls of the choroid plexus. Conditions have advanced past a defensive But that is not the only source, for in ap- phenomenon which might be comparable with a parently healthy fluids more cells are found in sterile serous effusion ilnto the synovial sac of the cisternw and lumbar sac than in the ven- the knee in the presence of a general or local trieles. Under abnormal conditions, however, infection in a lower limb. there is no doubt that cells come directly from A point to stress is that in the clinical con- the vessels into the perivascular spaces, as seen dition knowvn as serous meningitis, the outloolW in encephalitis, poliomyelitis, tetanus, etc. and the sequelae are much more favourable than Another very significant portal of entry for the onset of clinical signs and the cerebro- irritative substances is through the perineural spilnal fluid findings would lead one to suppose. lymphaties of the afferent and efferent cerebral We do not know whether these toxins (or in- and spinal nerves. fections) reach the central nervous system by Orr and Rows (Brain, xxxvi, 271), in an ex- the lymphaties, the perineural spaces, or the haustive paper, conelude that: "The precise blood vessels. It is possible that the toxin (or origin of the cells composing an inflammatory infection) may become centralized by way of reaction is always a matter of great difficulty, these routes, and when an acute clinical and some points must remain obscure, but a meningitis, amicrobic by direct smear and by consideration of the mechanism by which the culture, occurs concurrently with an acute is produced should prove of very febrile state (especially with infection in the great assistance, especially in the case of upper respiratory tract, ears, sinuses, etc.) we lymphogenous . In experimental may be dealing solely with a normal defence lymphogenous infection of the spinal cord of a reaction of the meninges, which does not subacute nature, in which all the inflammatory necessarily constitute a basis for serious appre- phenomena are extravascular, and the path of hension. Many clinical conditions are known the toxic lymph can be traced accurately, we to give rise to cytological and chemical changes find that besides the proliferation of the con- in the cerebro-spinal fluid. From this general nective tissue in the meninges the only strue- 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- II gives meningoeoccic serum were given intravenously; smear, the term "serous meningitis." Table negative; urine, normal. an analysis, from the present standpoint, of December 20th. Temperature 101.40; pulse 130; of serous meningitis of which respiration 32. He vomited immediately after taking twenty-four cases 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 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. to leave these in the Family history: excellent. Previous history: chicken- but have preferred rather pox, 1917; measles, 1919; appendicitis, 1920; tonsillitis, abstract by the use of the term "meningeal recurring attacks. to devote this brief discussion Present illness: six days ago he had a head-cold. irritation," and 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 namely, the relationship to the primary focus began. Temperature 99.60. A very restless 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 ears appeared normal; the tonsils were slightly con- sideration, namely, efforts to relieve the general 550 THE CANADIAN MEDICAL ASSOCIATION JOURNAL or local causative condition, and, secondarily, ever, for it is reasonable to expect that too the probable efficacy of repeated lumbar punc- frequent, or too complete, drainage might tend ture for the purpose of drainage. This latter to spread an otherwise localizing meningeal procedure is not without possible danger, how- condition.

IDIOPATHIC HAMORRHAGE OF THE NEW-BORN* BY JAMES L. MCCOLLUM Toronto VHAT is the cause of " idiopathic hawmor- often diffuse; signs of bleeding may be also hage of the new-born?" Is it due to an discovered in the pericardium, peritoneum, in infection? Is it brought about by the lack of the serosa of the lungs, and in any of the in- certain constituents of the blood? Is it caused ternal organs. Intracranial hwmorrhage is by a temporary deficiency of vitamine B in the usually subdural and may cover any part of blood of the infant? Or, shall we ever know the brain or extend into the spinal cord. Moyni- the underlying etiological factors of this dis- han points out a very definite relationship be- ease ? tween duodenal ulcer and melwna neonatorum, Idiopathic hamorrhage of the new-born is a and found ulcers in sixteen tvpical cases of this term used to designate a condition or disease in disease. Infection, necrosis, and thrombosis of infants which manifests itself shortly after birth the small vessels in the duodenal wall are given by spontaneous bleeding, and in which no birth. as causes for these ulcers. However, as melawna injury, other trauma, or other forms of disease neonatorum usually shows a rapid and unevent- have acted as causative factors. ful convalescence, it is hard to conceive that We can conveniently divide all cases of hoe- many cases have definite duodenal ulcer, or that morrhage of the new-born into two groups:- the ulcer is similar to that found in the duo- 1. Priminary, (also called "idiopathic.") denum of the adult. When extensive hawmor- 2. Secondary, associated with- rhage occurs intracranially most pathologists (a) Trauma. consider this to be the direct cause of death; (b) Infections. and Green states that extensive subdural bleed- (3) . ing may occur, either from trauma alone, or in In this paper it is the primary variety that I association with hwmorrhage of the new-born. wish to discuss, as "haemorrhage of the new- born" in toto is by far too extensive a subject OCCURRENCE AND DIAGNOSIS for the allotted time. Morbus hemorrhagica neonatorum is a rare disease, occurring in about 1 per cent of all PATHOLOGY births. The idiopathic variety is, of course, Unfortunately the pathology throws but little even rarer. Townsend3 judges it to be about one- light on the subject. All that we can find is quarter of one per cent, and states that he has h'wmorrhage, and, from autopsies we can do little found it to be more common in institutions than more than classify the areas or organs showing in private practice. Many observers state that the presence of blood, and find the parts most the incidence of the disease increases when often affected. epidemics of sepsis occur in hospitals, but Holt Hamorrhagic areas may be found in the has investigated this question carefully, and mucous membrane of the stomach and of the declares that he has found no increase among intestine; ecchymoses may be found in the skin, the cases of primary hamorrhage under such circumstances. *From the Sub-department of Pediatrics of the University of Toronto, and the wards of the Hospital The clinical picture of this disease is definite for Sick Children under the direction of Alan Brown. and easy to recognize. Medical advice is usually Read at the Pediatric Reading Club, January 120. 1928. sought very early for the child in this condition,