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 A CASE OF CEREBRO-SPINAL MENINGITIS ASSOCIATED WITH THE 
 MENINGOCOCCUS OF WEICHSELBADM. 
 
 BY 
 
 JAMES STEWART, M.D., 
 Professor of Merlicine, Mc(JilI University ; Pliysician to the Royal Victoria Hospital. 
 
 AND 
 
 V. F. MARTIN, M.D., 
 
 Lecturer in Medicine, McGill University ; Assistant Physician to the Royal Victoria 
 
 Hospital. 
 
 (HeprUiled from the Mon trail Mi dual ,Ji,vrnal, March, 1898.) 
 
A CASE OF CEREBRO-SPINAL MENINGITIS ASSOCIATED 
 WITH THE MENINGOCOCCUS OF WEICHSELBAUM. 
 
 BY 
 
 James Stewart, M.D., 
 Professor of Meditine, McGill University ; Physician to the Royal Victoria Hospital. 
 
 AND 
 
 C. F. Martin, M.D., 
 Lecturer in Medicine, McGill University ; Assistant Physician to the Royal Victoria 
 
 Hospital. 
 
 It is just a quarter of a century ago since the late Dr. Palmer 
 Howard published the first record of observations on Cerebro-Spinal 
 Fever in Montreal. This was in 1873, and during that period a small 
 epidemic occurred, the cases breaking out in various parts of the city, 
 as well as in the outlying districts. The published observations, how- 
 ever, are purely of a clinical character, and only one autopsy is 
 recorded, that by Drs. Roddick and John Bell, in which it is noted 
 that pus existed at the base of the brain and along the spinal cord. 
 The majority of cases recorded at that time had affected boys from 
 eight to ten years of age, some of the cases recovering, though, in the 
 majority, a fatal issue supervened. 
 
 It is interesting to observe at this time, a time when bacteriology as 
 a science had scarcely been created, the insistance which Dr. Howard 
 laid upon the specific poison which |he asserted must be associated 
 with the malady. The early appearaiice of the purpuric condition, 
 the general course of the disease, and its tendency to assume an epi- 
 demic character, all strongly favored the view that the disease was of 
 a zymotic nature. 
 
 Since that time a few sporadic cases have been recorded, the obser- 
 vations for the most part being again of a purely clinical nature. Dr. 
 Osier, in 1882, records in the Canada Medical and Surgical Journal 
 
the first satisfactory pathological examination of any case in this city 
 and since then a few isolated cases have been observed by Dr. Wyatt 
 Johnston, though in none of these whatsoever was there any bacterio- 
 logical examination made, other than to exclude the presence of 
 tubercle bacilli. 
 
 The opportunity having been afforded us in the past few weeks of 
 observing a similar case and obtaining satisfactory bacteriological 
 examination, we take this occasion to bring it to the notice of the 
 society, this being, to the best of our knowledge, the first instance in 
 Canada where the meningococcus of Weichselbaum has been demon- 
 strated at autopsy to be associated with cerebro-spinal fever, and the 
 first time that acute purulent pericarditis has been noted as a com- 
 plication. 
 
 The history of the case is of no little interest and affords a fairly 
 typical example of the character of this rather uncommon disease. A 
 young Canadian female aged 21 had been spending a few weeks in 
 Boston immediately prior to her illness, her domicile being in a healthy 
 and good locality. Quite a few cases, however, of cerebro-spinal fever 
 have been observed in that city during the past few years, though the 
 epidemic, it would appear, is now gradually dying out. During her 
 visit to Boston, the weather had been very good, and she felt in 
 excellent spirits. On the 28th of January, she returned to Montreal, 
 arriving in the evening, seemingly in perfect health. Early the next 
 morning she complained of chilly sensations, though to the touch her 
 skin was hot and dry. Very shortly afterwards vomiting supervened 
 and continued at intervals until the afternoon. Evidently the disease 
 had a very acute onset, for when Dr. James Bell, in answer to a 
 summons, saw her at half-past one in the aftex'noon, the facies seemed 
 indicative of collapse, the face being drawn, thin and pale ; she was 
 now suffering from severe headache mainly occipital and in the nape 
 of the neck. On examination, the temperature was 102°, the pulse 
 small and rapid, but there was otherwise no evidence of disease except 
 some tenderness over the lower portion of the abdomen. Upon the 
 next day her condition was worse, the headache was very severe and 
 she repeatedl)' cried out " Oh my head," referring the pain mainly to 
 the region of the vertex and the occiput. There was, however, no 
 more vomiting, and the abdomen was less tender, but the temperature 
 remained over 100°. There was no improvement evident during the 
 next 24 hours, and the patient showed distinct signs of delirium 
 Petechiee were now noticed for the first time upon the abdomen, and 
 there was general hypersesthesia. When addressed she m* rely com- 
 plained of the intense headache. On the same evening the patient was 
 admitted to the Royal Victoria Hospital, While beiug Jresjed for 
 
removal the rigidity of the neck was quite manifest, as also photo- 
 phobia. All night long after admission the rigidity was most marked, 
 and by the early morning the patient had become delirious. She 
 assumed the dorsal position with her legs slightly flexed upon the 
 abdomen. The pupils were equal and somewhat dilated, the tongue 
 was dry and cra',Ivo>iI, the temperature was 1045°, the pulse 110, and 
 the respirations 26. On this, the fourth day of the disease, the pete- 
 chise upon the trunk were more marked, and new ones had appeared 
 upon the arms. There was also a transient erythema upon the chest 
 and for the first time herpes developed below the left labial angle ; 
 and what was of still greater interest, upon the left side of the nose 
 and cheek. The rigidity of the body seemed to be more general, and 
 the nurse in charge noticed from time to time clonic spasms in the 
 upper extremities. By the afternoon delirium gave place to coma. 
 It should be here mentioned that the diagnosis of epidemic cerebro- 
 spinal meningitis having been made, the patient had boen carefully 
 isolated as a precautionary measure. In addition to the above symp- 
 toms, there was now noted increasing rapidity of the respirations, 
 general hypertonus of the muscles, flexion of the arms at the elbows, 
 and extension of the lower extremities, but there was no paralysis 
 anywhere. Strabismus was not evident. The thoracic organs showed 
 no special evidence of disease, and the abdomen was normal to palpa- 
 tion. The urine was turbid, contained a heavy sediment of urates, 
 was aciu In reaction, and had a specific gravity of 1023 ; there was a 
 large amount of albumin as also numerous granular casts of large size. 
 On the following day the temperature was still higher, 106.6°, and 
 the coma became deeper. The pulse now for the first time, became 
 distinctly irregular, but otherwise no special change could be c > erved. 
 The usual colour changes in the petechiee were manifest and n^ new 
 ones had appeared. Examination of the blood on this, the fifth day 
 of the disease, by Dr. Robins, the Resident Physician, showed the I'ed 
 cells to number 5,130,000, white cells 22,000, and the haemoglobin 75 
 per cent. Cultures from the blood of the finger, which had been 
 taken the day before on agar, serum and broth, all remained sterile. 
 On the following day, in the afternoon, the patient died, progressive 
 asthenia being the only noteworthy change. Lumbar puncture was 
 made the same afternoon, but the cultures resulting were contaminated, 
 and gave no evidence of the meningococcus. 
 
 The treatment adopted was of necessity purely symptomatic and 
 supporting, in this way diflfering to some extent from that adopted by 
 the late Palmer Howard, w^ho reconimended bromides, and iodides 
 with digitalis, and considered strychnine as contraindicated. 
 
 Autopsy. — The autopsy was performed six hours after death with 
 
the assistanco of Dr. A. C». Nichulls, urul the cotiflition found was 
 briefly as follows: 
 
 The body was poorly nourished, with rigidity markc<l in the jaw 
 and lower extremities ; the back was moderately livid. There, were 
 petechiue upon the al»domen and arms, and a few likewise on the back; 
 these varied in color accordinj,' to their ajije, presenting all gradations 
 from dark red to pale brown. Herpes was present upon the lower lip 
 and left side of the nose. Both wrists were redematous and slightly 
 swollen, but the other joints appeared normal. 
 
 Head. — The calvarium was moderately thick with deep arterial 
 grooves, the dura markedly congested, and the longitudinal sinus con- 
 tained pale mixed clot and some dark fluid blood. The inner surface 
 of the dura was reddened, but the dura itself showed no special 
 thickening, nor v^o it adherent to the iinderlying pia-arachnoid. On 
 exposing the arachnoid but very slight redema was present, while a 
 small (jjuantity of greenish-yellow gelatinous lymph was seen in the 
 subaiachnoid space. This exudate was situated mainly on the con- 
 vexity, along both sides of the longitudinal sinus and following the 
 lines of the larger vessels. Over the temporal areas there was com- 
 paratively little, and nowhere was there any pus between the dura 
 and the arachnoid. At the base of the brain there was likewise a 
 moderate amount of pus, more especially behind the optic chiasm and 
 ilie medulla, likewise between the cerebellum and the brain, and to a 
 less extent in the central groove between the two hemispheres. The 
 pia itself was distinctly adherent, quite oedematous and thickened. 
 In the Sylvian fissures no evidence of tuberculosis or other abnor- 
 mality could be ascertained. Upon opening the brain itself the 
 lateral ventricles were found of normal size, and in the right were a 
 few flakes of lymph, as also a few drops of fluid pus. The ependyma 
 
 was slightly 
 
 The third and fourth ventricles were free 
 The white matter of the brain contained numerous 
 
 granular. 
 
 from exudate. 
 
 puiietiform extravasations of blood, and the gray matter was likewise 
 congested, though to a less extent ; the cerebellum was soft and fri- 
 able, while the Itasal ganglia were congested and showed likewise 
 minute hsemorrhagos. The lateral sinuses contained dark fluid blood. 
 The bones at the base of the skull showed nowhere any signs of 
 disease. 
 
 Spinal Cord. — On removal of the brain a moderate amount of sero- 
 pui'ulent matter escape<l from the vertebral canal. The cord itself 
 was removed from behind, and after separation of the laminae the dura 
 was seen to be tensely expanded in various parts of its course irregu- 
 larly. The vessels about it were congested. On slitting up the dura 
 
 I 
 I 
 
 I 
 
 I 
 
I 
 I 
 
 the posterior surface of the pia-arachnoid was seen to contain numer- 
 ous patches of lymph in the sub-arachnoid space ; these existed as 
 either fusiform collections of pus or were spread out in broad plaques 
 over the posterior surface of the cord. There was distinct tedenia of 
 the pia, and in places it was markedly thickened. On section at vari- 
 ous levels of the cord marked congestion was the main feature pre- 
 sented, but there seemed to be no evidences of punctate heemorrhages. 
 
 With reference to the organs in general, the main conditions pres- 
 ent were acute purulent pericarditis, oedema and partial collapse of 
 the lungs, with acute bronchitis; obsolescent apical tuberculosis 
 with left adhesive pleurisy, acute parenchymatous nephritis and ca- 
 tarrhal enteritis. The spleen was of normal size, and there was no 
 further evidence in general of a septicaemia. 
 
 Bacteriological Examination. — Fresh coverslips, taken directly 
 from the purulent exudate from the cerebral and spinal meninges, 
 showed it to con.sist mainly of pus cells, fibrin, granular and colloid- 
 looking masses. Some of the cells were of enormous size, three to 
 four times that of an ordinary pus cell, containing large nuclei ; some 
 appeared to be vacuolated, and in a large number there were cell in- 
 clusions. Other cells, again, seemed much more ill defined, and their 
 nuclei were irregular and fragmented. The leucocytes present were 
 for the most part of the polynuclear variety. Specimens were stained 
 by various methods, some with Loffler's blue, others with fuchsin, saf- 
 franin and also by Gram's method. With Loffler's blue one saw 
 semmel-shaped diplococci, resembling very much the gonococcus, 
 except that the size varied very much and that they tended, further, 
 frequently to form tetrads. The staining, too, was extremely irregu- 
 lar, some, and particularly the larger ones, taking up an almost black 
 color, while others adjacent to them might be scarcely stained at all. 
 While many of these were found within the cells, a very large num- 
 ber were constantly found free, our experience in this respect being 
 quite at variance with that of Weichselbaum, Councilman and others; 
 with this exception, however, the coverslip preparations corresponded 
 in all respects to the descriptions given by these authors. On 
 staining by Gram's method, the bacteria became decolorized. 
 
 Coverslips from the pericardial exudate showed likewise a pure 
 culture of the same micro-organism, while others made from the 
 larger bronchial tubes showed similar cocci mixed with numerous 
 other forms. In the largest bronchi there were chiefly lanceolate 
 diplococci and the meningococcus above described. Coverslips were 
 likewise made from the spleen and liver pulp, from the heart blood 
 and the bile, but in none of these instances did we obtain any bacteria. 
 
secretions and demonHtrated the presence of the micro-organiam in 
 stained coverglass preparations. 
 
 (Julturea were made from the various tissues and organs of the body 
 on different media, tiie most abundant growths being ol)tained on 
 glycerinated agar. On this medium the exudate from tiie meninges 
 jjave an abundant growth after thirty hours, appearing at first as 
 pearly gray dots, spreading out in piaijues over the surface of the tube 
 and gradually assuming a more grayish, opaque appeaiance. On 
 staining with the various reagents above mentioned, the results were 
 identical, and no definite chain formations were seen on this medium. 
 On being tran.sferred from the agar to broth, the growth ;S again 
 abundant, appearing mainly in the sediment, the .supernatant fluid 
 remaining fairly clear. The diplococci were here for the most part 
 large and arranged distinctly in chains, containing from four to eight 
 cocci in each. Some of the chains, however, were made up of very 
 much smaller organisms, resembling the ordinary pyogenic strepto- 
 cocci ; that they were, however, of the same nature as the other 
 diplococci was proven by their negative reaction to Gram's method. 
 Cultures on glycerinated agar and broth from the pericardial exudate 
 gave likewise pure cultures of the meningococcus. From the heart 
 blood, the liver, the spleen and the bile, cultures taken on various 
 media remained sterile. From the lung a mixed culture of staphylo- 
 cocci and lanceolate diplococci was obtained. While most observers 
 have found agar the most suitable culture medium, it may be stated 
 that the Boston bacteriologists have met with best results in employ- 
 ing blood serum ; the differences are in all probability associated with 
 the chemical reactions of the media. Inoculations of a three-days- 
 old broth culture subcutaneously into a guinea-pig proved innocuous, 
 as did also the intravenous injection into a rabbit of a 24-hour-old 
 broth culture. It has been shown repeatedly that the life of these 
 bacteria is extremely short, and transfers every second or fourth day 
 are necessary to keep the germs alive. Hence a three days' growth 
 might readily prove harndess to a guinea-pig, though the fact that 
 recent growths were innocuous when introduced into the circulation 
 is of no little interest. 
 
 Sections were made of the various organs and tissues of the body ; 
 those from the brain and meninges, including the exudate, showed 
 mainly great dilatation of the blood vessels, with recent punctiform 
 haemorrhages and large collections of polynuclear leucocytes, with ex- 
 treme fragmentation of the nuclei. Extensive areas of necrosis were 
 likewise manifest in the nerve tissue. The micro-organisms were by 
 no means easy to detect, the specimens stained with saffranin giving 
 the best results. In the spinal cord the same condition was evident, 
 
Imt the more minute changes in the cellular elements arc still under 
 investigation. Sections from the other organs showed no features of 
 sp»!cia] interest in connection with the case. 
 
 The presence of a pericardial exudate containing the meningococcus 
 is (juite evidently of extreme rarity, and the entire absence of fibrin 
 on the serous coats is remarkable in view of tha amount of pus 
 present. 
 
 It will be seen, then, from the foregoing that the case recorded was 
 quite evidently of the nature of an epidemic cerebro-spinal menin- 
 gitis, while the organism assof'iated with the lesions is undoubtedly 
 the meningococcus described by Weichselbaum in 1886, and much 
 more fully within the last twelve months by Dr. W. T. Councilman, 
 of Boston. As is already well known, it has been generally accepted 
 until quite recently that this malady is due to the diplococcus lanceo- 
 latus, while the organism described by Weichselbaum has been prac- 
 tically disregarded. 
 
 Observations made, however, since 1895, more especially by Jeeger, 
 of Stuttgart, and Councilman, Mallory, and Wright, of Boston, ren- 
 dered it undoubted that in the epidemic form of this disease, not the 
 pneumococcua, but the meningococcus of Weichselbaum is the chief 
 etiological factor. The above-mentioned Boston pathologists had 
 occasion to examine thirty-five cases post mortem, and the meningoco- 
 ccus was found in all but three cases. Certainly no such complete series 
 of observations of any epidemic has hitherto been made commensurate 
 with these, and the uniformity of their results in examining .so ex- 
 tensive a material, places the nature of the disease beyond any doubt. 
 It is true that in a number of cases the pneumococcus has been fre- 
 quently found in pure culture, but so far as we are aware, it has 
 never been demonstrated with a satisfactory uniformity. Flexner 
 and Barker, of Baltimore, have recently published a most interesting 
 and valuable article giving a detailed account of the conditions under 
 which an epidemic of cerebro-spinal meningitis had occurred in a 
 small mining town of Maryland. Sixty-eight patients were observed 
 but unfortunately it was po.^sible to obtain autopsies in only two in- 
 stances. The pathological lesions in these cases are most minutely 
 described, and the bacteriological examinations would seem to indicate 
 that the pneumococcus was the chief organism present. Smears made 
 from the exudate on the meninges showed a lance-shaped diplococcus 
 which stained by Gram's method, but the cultures and inoculation 
 vest did not afford very satisfactory results. The authors, however, are 
 of the opinion that the pneumococcus was undoubtedly present, although 
 the trying circumstances under which the investigations were made 
 rendered it impossible to obtain eminently satisfactory results.