[Reprinted from The Philadelphia MojiXttfcY MkiIical Journal, of jUtQJuly0p"-i9u5 iM EPIDEMIC CEREBROSPINAL MENINGITIS: REPORT OF THIRTY-FOUR CASES, WITH ESPECIAL REFERENCE TO THE BACTERIOLOGIC FEATURES OF THE DISEASE* By R. B. H. GRADWOHL, M.D., of St. Louis, Mo. Bacteriologist to the St. Louis City Hospital, etc. The attention of the medical world has been fre- quently called to epidemic cerebrospinal meningitis during the past few decades, and, by means of the almost perfect methods of bacteriologic research now in vogue, very satisfactory results have been ob- tained in ascertaining the true character of the dis- ease in its recent visitations with us. We find in recent years that several rather extensive epidemics have been reported by competent bacteriologists, viz., that of Barker and Flexner of an outbreak at Lona- coning, Maryland, in 1893 j1 that of Jaeger, of an outbreak in the garrison at Stuttgart in 1895 f that of Councilman, Mallory and Wright, of an epi- demic which raged in Boston through the winter and spring of 1897 ;3 and lastly that of Class, who has very recently described an epidemic in Chicago dur- ing the year 1898.4 It has been my good fortune to have seen 34 cases of this disease during the past winter and spring, as part of the epidemic which has been raging in St. Louis. All of these cases were seen by me in the wards of the St. Louis City Hos- pital, where I had the opportunity of studying the disease from a clinical, bacteriologic, and pathologic standpoint. My bacteriologic and pathologic work was carried on in the laboratory of bacteriology, ♦From the Laboratory of Bacteriology of the Medical Department of. Washington University. 2 medical department of Washington University. I wish to express my indebtedness to Dr. Amand Ravold, professor of bacteriology in the medical de- partment of Washington University, for many favors extended to me while doing this work. In looking over the literature upon this subject, I have been greatly impressed by the superiority of the reports of the epidemics just quoted over the reports of earlier epidemics at home and abroad, beginning with the first definite description of an epidemic of cerebrospinal meningitis by Vieussieu, in Geneva, in 1805.5 We are not justified in accepting the reports of probable epidemics of this disease which occurred before the beginning of this century, as the accounts are meager, unsatisfactory and indefinite, so far as a positive establishment of the disease-outbreak is concerned. Hirsch divides the outbreaks of the dis- ease into 4 periods : the first, from 1805 to 1830, in which the disease prevailed principally in the United States; the second, from 1837 to 1850, when it pre- vailed principally in France and extended from France into Algiers, being carried by the French troops on their Algerian campaign; the third, from 1855 to 1875, when it prevailed principally in Ger- many ; and the fourth, from 1875 to the present time, in which the disease has appeared in small epidemics in a number of places, both in Europe and in this country. It seems strange that the first definite description of the microorganism which is now justly held to be the specific cause of epidemic cerebrospinal meningitis was considered by Weichselbaum, its discoverer, to be the cause of sporadic cerebrospinal meningitis.6 Weichselbaum, in 1887, reported 6 cases of cerebro- spinal meningitis in which he discovered a microor- ganism which he called the diplococcus intracellu- laris, because it was found within the pus-cells of the cerebrospinal fluid. He did not, however, see its re- lationship to the disease as it exists in epidemic form. It was not until the report of Jaeger’s 12 cases in the garrison at Stuttgart7 that attention was called to the diplococcus intracellularis as the proba- ble specific microorganism of epidemic cerebrospinal 3 meningitis. Since that time, in all the epidemics which have been reported, that microorganism has been almost constantly present. There has been some dispute as to the identity or the nonidentity of the diplococcus intracellularis and the diplococcus pneumoniae. Barker and Flexner say8 that in the epidemic which they studied at Lo- naconing they discovered a microorganism which, while behaving much like the micrococcus lanceola- tus, might have been a variety of the diplococcus in- tracellularis meningitidis. In other words, they as- sume that there is probably some relationship between the diplococcus intracellularis and the micrococcus lanceolatus, not only morphologic but also biologic. On the other hand, we must take into consideration 1. 4 the disparity between these two microorganisms in their morphologic, cultural and pathogenic character- istics. Councilman, in the Boston epidemic of 1898, found the diplococcus intracellularis in 111 cases, and thus proved its constant presence, adding another confirmation to the statement of Jaeger that this is the essential etiologic factor in the production of Fig. 2. pidemic cerebrospinal meningitis. More recently, Class has studied an epidemic of 38 cases in Chi- cago.9 It is unfortunate from a statistical point of view that he was only able to perform lumbar punc- ture in 5 of the 38 cases ; nevertheless, he found the diplococcus intracellularis in these 5 cases and would undoubtedly have found it in the other cases had not adverse circumstances forbidden the performance of 5 lumbar puncture. In the 34 cases which I have seen the diplococcus intracellularis was demonstrated both in fluid obtained by lumbar puncture and from the meninges postmortem, in 33 instances ; the micrococ- cus lanceolatus was found in the other case. This case in which the micrococcus lanceolatus was found was in its clinical behavior identical with the cases pro- Fig. 3. duced by the diplococcus intracellularis. No other explanation for its presence can be found than that it was a sporadic case which had become entangled in the whirl of the epidemic cases. Confronted with the bacteriologic findings in these several epidemics, we are warranted in accepting the diplococcus intra- cellularis as the specific microorganic exciting agent in the production of epidemic cerebrospinal men- ingitis. % 6 In my investigation of this microorganism, I have followed the plan laid down by the Committee of American Bacteriologists in their report to the Com- mittee on the Pollution of Water-Supplies of the American Public-Health Association.10 This outline covers the subject completely from a bacteriologic point of view, and I can do no better than to submit Fig. 4. my description of this microorganism in the form ad- vised by this committee. It may be well to speak of the extreme difficulty of cultivating the diplococcus intracellularis upon the ordinary culture-media—a fact already pointed out by Councilman.11 The mi- croorganism seems to thrive best on Loffler’s blood- serum and it was upon this medium that my inocula- tions were first made; later, the other media were 7 inoculated and thus the microorganism was studied thoroughly. Had I immediately inoculated or plated the microorganism upon agar, it is doubtful whether a growth would have been obtained. Photographs of the colonies were taken—a procedure especially rec- ommended by the committee. The diplococcus intra- cellularis is considered by some to be allied to the gonococccus since the method of division, the cul- tural behavior and the fact that it is found within the pus-cell are identical characteristics of both micoor- ganisms. Ghon, of Vienna, has given a description of this microorganism and claims that it corresponds in cultural behavior to the gonococcus of Neisser. Ghon and Jaeger found the meningococcus in the nasal secretions in many of these cases, and I have been able to do so in many instances. No record is found in Ghon’s cases of a demonstration of the microorganism in the purulent discharge from the ear. In nearly all the cases which were complicated by purulent discharge from the ear, I was able to re- cover the diplococcus intracellularis. My experience has been that the Gram method of staining as a differential test between the diplo- coccus intracellularis and the micrococcus lanceolatus has but little value. In many of my cases I found that the diplococcus intracellularis would be decolor- ized, according to Gram, and in other cases it would retain its color: again, in some cases, the diplococcus intracellularis would be stained, according to Gram, after being grown for but a short time, and when suc- cessive transfers had been made, and the microorgan- ism had passed through the cycle of cultural life for a week or two, it would show a decolorization when subjected to the Gram method of staining. In the same cover slip preparation, some diplococci would be deeply stained, and others very feebly. The complete description of the microorganism now follows : Source.— i. Cerebrospinal fluid, obtained from man by (a) lumbar puncture, (b) postmortem specimens. 2. Brain and spinal cord tissue. I.—MORPHOLOGY. 8 3. Cerebrospinal fluid, pus, cerebral and cord tissue of animals used for experimental inoculations, viz., dogs, cats, and a rabbit. 4. Secretions from the nose and ear. 5. Pulmonary tissue of man and animals dead of secondary pneumonia. Habitat.—Cerebrospinal fluid; intrameningeal spaces, nose, and ear. Morphologic examination of agar-culture, grown 28 hours, at i8°-20° C. ; ditto, grown 28 hours, at 360- 38° C.; ditto, grown for 48 hours, at 36°-38° C.; ditto, grown for 60 hours, at 36°-38° C. Morphologic examination of Loffler’s blood-serum culture (as above). Morphologic examination of gelatin culture (as above). Morphologic examination of broth (as above). Morphologic examination of glycerin-agar (as above). Morphologic examination of potato (as above). Morphologic examination of milk (as above). Morphologic examination of litmus milk (as above). Diplococcus ; tetracoccus in a few cases; in few cases, chains of not more than six. Size.—About size of gonococcus. Great variation in size was noted : as seen in the pus-cell, the diplo- cocci were about the size of the gonococci; when sep- arated in pure culture, they became a little larger, and they increased in size in proportion to the num- ber of transfers that were made, i. e., at the end of 2 weeks, if transfers were made daily, the size of the mi- croorganism far exceeded its original size. They also varied in size with the character of the culture upon which they were grown ; they attained the largest size upon agar, and retained their size most uniformly upon Loffler’s blood-serum. It stains with the standard watery dyes easily, especially with fuchsin. It is decolorized by Gram’s method in some cases, and retains its color in others, as above stated. No capsule observed. No spore-formation. No vacuoles observed. Fig. 6.—Cerebrospial meningitis—Compilation of cases. Fig. 7.—Graphic representation of epidemic of cerebrospinal meningitis. 9 No crystals observed. Non-motile. Pleomorphism, as above noted. Growth, at i8°-20° C., is less abundant than that at 36°-38° C. Thermal death-point, 550 C.; time of exposure, 10 minutes; permanence of morphologic characters . . yes. Optimum temperature, 38° C.; growth limited; maximum, 50° C.; minimum, 180 C. Optimum reaction of media, from 3.5% more than neutral. II.—BIOLOGY. Gelatin Plate. Deep Colonies. Size, 2 to 3 mm. Rather circular. Margin, dark. Texture, homogenous. Faint growth under mica plate. {Neutral.) Surface Colonies. Size, 3 to 4 mm. Round. Margin, lighter than cen- ter. Texture, granular and wavy. Agar Plate. {Neutral.) Deep Colonies. Little larger than gelatin. Round. Dark margin. Granular. White. Surface Colonies. Same as gelatin. Round. Light margin. More coarsely granular. White. Gelatin Tube. {Neutral.) Puncture:— One inch and a half in length. Straight, linear puncture. Faint line, white color. Faint growth along stroke. More abundant growth on surface. 10 Streak:— Flat, straight, tapering towards the top. Thicker in middle, margin less dense. Does not stand up above the surface to any extent. Transmits light moderately. Dull, reflecting light poorly. White in color. Lustre is dull. Fig. 5.—Cultures of the Diplococcus Intracellularis Meningitidis : 1. Milk, showing coagulation. 2. Potato, 30 hours old. 3. Bouillon, 24 hours old. 4. Glycerin-agar, 30 hours old. 5. Loffler’s blood-serum, 24 hours old. 6. Plain agar, 24 hours old. Change in medium :— No change in consistence, color, or odor. Agar Tube. Neutral. Streak:— Two and a half inches. Grows in a wavy line, about 2.5 mm. wide. 11 Growth at first is limited to the appearance of a few small white points along the streak; these points grow larger after 18 hours, and, as they increase in size, more small points appear, and, at the end of 28 hours, they have coalesced, and formed one continuous white streak. The streak shows the primary con- struction of points for 30 hours by minute protuberances which project above the sur- face ; but after that time the surface becomes level. Surface relief accordingly is well marked. Light is transmitted for 20 hours, but not there- after. Light is reflected from the individual colonies before coalescence, but not after the forma- tion of the streak. White in color. Luster is dull. Change in medium :— No change in color, consistence, or odor. Nutrient Bouillon in Test-Tube. It becomes turbid at 38° C., after 18 hours. Clears on standing. On shaking, masses are seen to arise from the bottom of the tube. No change in the color of broth noted ; no formation of pellicle. Milk. No visible change in 24 hours at 38° C. Does not curdle in 48 hours at i8°-20° C. ; curdles in 48 hours at 36°-38° C. ; curdles on boiling. In litmus-milk, the red color, showing acid reaction, is developed, after 24 hours at i8°-20° C., and in 12 hours at 360- 38° C. No odor is developed. The curd forms in small fragments. Glucose Bouillon in Fermentation-Tube. In the bulb, the fluid becomes turbid, and a fine, flocculent mass forms in the connecting tube, while the fluid in the closed tube remains clear at the ex treme top, but is slightly turbid in the lower part. 12 This clears on standing for 6 hours. No color de- velops. Potato. Growth occurs in the form of a shining, yellowish- white, viscid, smeary substance, after 18 hours at 36° to 38° C. Loffler’s Blood-Serum. After from 15 to 18 hours, minute white colonies appear, separated from each other by a distinct inter- val. These colonies increase in size and others at the same time appear, so that at the end of 24 or 26 hours, a white streak covers the surface. It still shows its primary construction in that the white, sep- arated colonies stand up above the surface. A further change noted at the expiration of 30 hours is the change in color from an almost pure white to a dull, brownish-white color. At the end of 48 hours the growth is dead so far as further growth in other tubes which are inoculated is concerned. No pigment is developed in the medium. The microorganism dies within two days if it is not transferred to a fresh tube. One tube of the micro- organisms can remain virulent for 70 days, according to Ghon ;12 in order to do this, the cultures should not be allowed to dry out, and they should be kept at a temperature not below 250 C. It is an aerobic, facultative anaerobic microorgan- ism. It is said to be pathogenic for dogs, cats, rab- bits and guineapigs. My inoculations upon animals were limited to dogs, cats, and one rabbit. The re- sults of these experiments are highly interesting, as an attempt was made to show a correspondence be- tween the virulence of the microorganism in a par- ticular case in man with the virulence of the fluid or culture from that case when injected into the lower animals. In nearly every case this was demonstrated conclusively. Six dogs, 12 cats and 1 rabbit were inoculated. In the first two experiments upon dogs, trephination was resorted to as a means of introducing the microorganisms into the cranial cavity; this was afterwards modified by the use of a long exploratory needle and syringe by which the animals could be 13 quickly and just as surely inoculated with the diplo- coccus intracellularis. It is also a curious fact that the dogs manifested symptoms more closely approach- ing the disease as it is seen in man than did the cats. The first dog was inoculated with material from a man who had succumbed to the disease in 24 hours after the onset; this dog died in convulsions 6 hours after coming out of the anesthetic. The second dog was inoculated with material from a man who had succumbed to the malady 2 weeks after the initial symptoms, and this dog lived 10 days, finally dying in convulsions. This second dog began to show symp- toms on the second day following the inoculation, lying on its back, with rigidity of the spine, and would not partake of food for 3 or 4 days. It began to have convulsions on the tenth day and died in opis- thotonos. The temperature of this dog was taken before the inoculation, and it was ioo° F. It had an average temperature of 104° to 107° F. until its death. The third dog was inoculated with cultures obtained from the second dog postmortem, and it died in about 2 weeks, displaying about the same conditions as the second dog. A fourth dog was inoculated with a pure culture of the diplococcus intracellularis taken postmortem from a pregnant woman who had lived but 2 days after the acute onset of the disease, and this dog lived 4 days, finally dying in convul- sions. The fifth dog was inoculated with a pure cul- ture obtained from the fetus of the above woman, and this dog died 2 days thereafter, in convulsions, as did another dog which was inoculated from cul- tures from the mother’s ear. The dogs all manifested symptoms referable to the disease in some way or another: they had convulsions, had a febrile tempera- ture and showed that they were acutely ill. The results of the inoculations upon cats were equally gratifying in so far as a correspondence be- tween the virulence of the infection in the patient and the virulence of the material from that case when in- oculated into the cats was concerned. The cats did not, however, show evidences of the disease in the way of symptoms as did the dogs. Three of the cats had convulsions antemortem, but the other 9 did 14 not have them. One cat had marked opisthotonos while the others did not. One cat was inoculated with cultures obtained from a patient who subse- quently recovered after being sick 6 weeks ; the cul- tures were taken at the end of the third week of the disease. This cat apparently recovered after being confined for about one month ; the cat was killed with chloroform, and at the autopsy some thickening of the meninges was found but no exudate. Cultures taken from the meninges were barren of growth. This was the only cat that was not killed by the disease. It may be well to add here that postmortem examina- tions were made upon all the animals, and cultures were thus obtained. The pathologic conditions found in these animals corresponded closely to those found in man, of which mention will be made later on. In order to demonstrate the fact that the diplococcus intracellularis is the essential cause of the secondary pneumonia which is sometimes found in connection with epidemic cases of cerebrospinal meningitis, I injected pure cultures of the microorganism into the pleural cavities of two cats : they died after 2 days and at the postmortem examination typical croupous pneumonia was found. The diplococcus intracellu- laris was recovered in pure culture from these pneu- monic lungs. No signs of meningitis were found at autopsy in these two cats. The rabbit which was inoculated died after 2 days, being killed with cul- tures from a patient who had lived but 2 weeks after primary infection. Thus the pathogenesis of the diplococcus intracellularis was clearly proved. Of the 34 cases seen by me, 22 were "fatal and 12 resulted in recovery—a mortality of 64 Au- topsy was held in 21 of the fatal cases, the body of the twenty-second man having been removed by his family before we had time to conduct a postmortem examination. The findings in these cases were nearly parallel both as regards microscopic and macroscopic results. It is for this reason that the pathology of the affection is discussed in toto. In this place it is incumbent upon me to speak of the great value of lumbar puncture as a diagnostic measure in cases of supposed epidemic cerebrospinal meningitis. It is an absolutely harmless procedure and in some cases in which there is an abundant exudation of a serous nature improvement seems to follow its performance; this was noticed in one case by me. Lumbar punc- ture offers the only means of a differential diagnosis between a sporadic and an epidemic case of cerebro- spinal meningitis. In the cases reported, lumbar puncture was performed in every instance save one, and in the fatal cases the microorganism was also separated from the tissues. As stated above, the micrococcus lanceolatus was demonstrated #in the cerebrospinal fluid and in the tissues postmortem of but one case. The puncture should be made on a level with the crest of the ilium and the aspirating needle should be directed slightly upward and inward, the point of the needle puncturing the skin about one half inch from the spinous processes to either side. By feeling the way in, the needle readily enters the spinal cavity. If the fluid does not flow rapidly, the patient should be elevated in bed by raising the shoulders. It is recommended not to resort to the use of the aspirating syringe. The postmortem findings in these cases were uni- form and will be discussed accordingly. The gross pathologic lesions consisted, in the acute cases, of a great injection of the vessels of the pia arachnoid with a purulent exudation over the meningeal sur- faces. In some cases this exudation of pus was con- fined exclusively to the base of the cerebrum, but in other cases it could be made out over the entire sur- face of the meninges. In all the cases the same purulent exudate was found spread over the pia arach- noid of the cord. In the very acute cases—cases which survived but a day or two after the onset—hy- peremia of the pia arachnoid alone was present or predominated over the purulent exudation. The cerebral tissue was softer and more friable than it is in other conditions. Upon opening the ventricles by the usual “postmortem incisions” they were found to contain a purulent fluid in greater or less amounts in different cases. In some cases there was only a smeary coat of pus lining the ventricles, while in other cases the purulent exudation into the ventri- 16 cles was so great that it amounted almost to a hydro- cephalus internus. When the purulent exudation was confined mainly to the base of the cerebrum, there were strong adhesions between the cerebrum and the cerebellum due to the organization of this purulent mass. Sections of the meninges, the cere- bral and cord tissues, cranial and spinal nerves were hardened in Zenker’s fluid and alcohol and imbedded in celluloidin. The intracellular diplococci were demonstrated in these sections by staining with eosin followed by Unna’s methylene-blue. “The advan- tage of Unna’s methylene-blue, which is more alka- line than Loffler’s, is that it stains bacteria and nuclei in tissues hardened in Zenker’s fluid, which gives a more pefect fixation of the tissue-elements than either alcohol or sublimate.”13 The meninges showed mainly purulent infiltration. The most marked path- ologic change in the gray matter was the increase in size in the neuroglia-cells with an increase in the nu- clei of the protoplasm. In sections of the cord, stained by Nissl’s method, the two changes already pointed out by Barker were noted :u a disintegration in the stained section of the individual Nissl bodies, especially in those of the dendrites and of the periphery of the cell-body; secondly, a breaking down in the center of the cell and a displacement of the nucleus to the periphery of the cell. These two changes are due, first to the direct action of the bacteria upon the tissue in con- tiguity to the meninges of the cord ; secondly, to the fact that axones of these cells are injured on the sur- face of the cord and consequently the second change takes place, i. e., a breaking down in the center and a displacement of the nucleus to the periphery of the cell. This second effect is nothing more or less than the “ reaction at a distance of Marinesco.” This secondary effect, as seen particularly in the nucleus of Clark’s column, is due to the fact that axones de- rived from that nucleus and running in the direct cerebellar tract are superficially placed in the medulla, where the purulent exudation is ofttimes greatest in these cases. The cranial nerves showed various de- grees of degeneration and inflammation, particularly 17 the second and eighth. In some cases pus was found within the eyeball, coincidently with the existence of a choroiditis. It is an open question whether pus follows the course of the optic nerve into the eye or whether it is formed within the eye as a kind of metastatic process of meningitis. It has been said by Dr. John Green, of St. Louis, that he has known of cases of this disease in which the pus seemed to form within the eye—sometimes to a great extent and even so much as to completely fill the eye, push- ing out the vitreous and perforating the cornea. In view of this fact we may say that the existence of pus within the eye is a complication and not part of the meningeal trouble. The auditory nerve showed dis- tinct degeneration, as did some of the spinal nerves. Examination of the other organs revealed the im- press of the toxic condition, i. e., acute hemorrhagic nephritis, septic spleen in some cases, myocarditis, pneumonia and a gangrene of the lung in one in- stance. These 34 cases of epidemic cerebrospinal meningi- tis when considered as a whole give us a beautiful picture of the symptomatology of this affection. In this group of cases, every symptom which has been described as belonging to this disease was found, and indeed some of the individual cases displayed a clin- ical aspect in perfect accord with the type of the affection. It is for this reason that I prefer to dis- cuss the symptomatology of the epidemic as a whole and not seriatim. Not only will words be saved by this method, but it is hoped that the clinician will be more fully impressed with the symptoms found. I have prepared a chart of these cases with a list of symptoms as recorded by the health-department of the city of St. Louis in their recent investigation of the recent St. Louis epidemic. A graphic represen- tation of these cases is also appended. I will briefly narrate these symptoms, with ages of the patients and duration of the disease. The oldest patient was a woman of 53 years ; the youngest, a child of 9 days. A majority of the cases occurred among adults over 16 years of age. There were 20 males and 14 females. In some of the cases it was impossible to obtain a 18 complete family and personal history, as they came to the hospital unaccompanied. The sanitary condi- tions to which these patients were subjected before their illness were in all but 2 cases definitely known to have been very bad. In the majority of cases it was found that squalor and filth could be impartially said to have played a part in the infection of the pa- tient with meningitis. In 15 cases the onset of the disease was marked by a chill. In every case the sign of Kernig was present, thus adding another con- firmation to the statement of Herrick,15 “that the sign of Kernig is as pathognomonic of meningitis as the rose-spots of typhoid fever or the murmurs are of endocarditis.” As early as 1882, Kernig, of St. Peters- burg, called attention to this sign, which he thought was found only in affections of the pia mater and which was never lacking in inflammations of that membrane. This was subsequently confirmed by Henoch, Bull, Bilim and Friis. Netter16 later con- firmed these observations and cited cases. The sign of Kernig is elicited in the following way: the pa- tient is placed in dorsal decubitus, care being taken that the legs are relaxed and fully extended at the knees. When the patient is raised in bed by the shoulders, it is found that the knees are more or less flexed, and, despite all efforts, cannot be extended on account of contracture of the posterior muscles of the thighs. Complete extension becomes possible when the patient is placed upon the back again. It is de- pendent upon a marked flexor contracture. Netter15 found this sign present in 41 instances among 46 cases of meningitis of different kinds, or about 90%. Herrick has recently made observations upon this sign in 19 cases with 6 autopsies.17 It was present in 17 of these cases, and in 2 in which it was not found but a single examination was made only a short time before death when there was a general laxity of all the muscles. It was, therefore, of considerable value in some of the cases as a means of diagnosis. Net- ter18 believes that the presence of this sign confirms the diagnosis of meningitis when the symptoms are obscure and suggests a latent meningitis when it is the only symptom present. In 25 healthy patients 19 examined by Herrick this sign was not present. In ioo cases of patients sick with other diseases, it was present but twice and absent in 98 cases. Difficulty of deglutition was present in 31 cases; projectile vomiting was present in 22 cases. Diar- rhea was noted but twice ; joint-affections were pres- ent in only 2 cases. Herpes labialis was present in 21 cases; an eruption, either petechial or maculo- papular, was present in 21 cases. Orthotonos was present in 15 cases, and opisthotonos in 26 cases. Tache cerebrale was noted in 26 instances. Head- ache, retraction of the head, and pain along the spine were constantly present. Delirium was present in every case save 3. Coma was present in 14 instances. Paralysis was a symptom found in 10 cases, and in- cluded ptosis, strabismus, and auditory involvement. Tremors, particularly of the lingual and facial muscles, were noted in 28 cases. The patellar reflex was exag- gerated in 18 cases, normal in 6, and absent in 10 cases. Croupous pneumonia was made out in 3 instances. The pulse was rapid in all the cases ex- cept 2; one of the patients, with a slow pulse, died, after being sick 2 days, while the other recovered, after an illness of 20 days. The urine showed the following reactions : albumins in 20 cases ; sugar pres- ent in 2 cases ; diazo-reaction positive in 17 cases, and absent in 17. Casts, epithelial and granular, were found in 3 cases. Instability of the pupil was made out in 31 cases. Nystagmus was present in 13 cases. Otitis media purulenta was present in 4 cases. Pha- ryngeal trouble was noted once. Retraction of the abdomen was noted in 27 cases, and absent in 7. The duration of the disease varied from 2 to 37 days, an average duration of I4T\ days. In Case III, there was a history of an attack of convulsions on the day before en- trance into the hospital. In Case XIII, there was a statement from the patient’s father, saying that his son (patient) had been struck on the back of the neck with an iron wheel on the day before taken acutely ill; he did not, however, manifest any symptoms of concus- sion at the time of the receipt of the injury. Case XX had a well-marked bulging of the fontanelle., We have in Cases VIII and IX the only probable instance of 20 contagion in all the cases. Case VIII was taken ill on one day, and, on the following day, its playmate, Case IX, was similarly affected. Of course, both might have been infected from the same source, and not one from the other. In no case was I able to trace any conveyance of the disease from one patient to another. We must take into consideration the ex- treme difficulty of following the movement of patients in a large city like St. Louis. Among these 34 cases of epidemic cerebrospinal meningitis, there was one of transmission of the disease in utero, as demonstrated by pathologic and bacteriologic findings. I will make this the subject of another paper, and will present it before this Association if it be desired. In conclusion it can be said of this disease in gen- eral and of its manifestations in these cases in par- ticular, that— 1. It is a specific infectious disease. 2. It is not highly contagious, but only contagious in the sense that tuberculosis pulmonalis is conta- gious.19 3. The diplococcus intracellularis meningitidis is the prime etiologic factor in the causation of epidemic cerebrospinal meningitis. 4. In all suspected cases of meningitis, lumbar puncture should be resorted to as a means of differen- tial diagnosis between an epidemic and a sporadic case. 5. The Gram method of staining is a rather uncer- tain means of differentiating the diplococcus intra- cellularis from the micrococcus lanceolatus. 6. The diplococcus intracellularis is especially pathogenic for dogs and cats. 7. The virulence of the infection, i. e., of the dip- lococcus intracellularis, varies in different cases and in different periods of its visitation upon the same patient ; that the virulence of the infection tends towards an attenuation with the further progress of the disease and that in the more chronic cases which have gone beyond the period of one month, the viru- lence of the infection is almost lost. 8. The sign of Kernig is pathognomonic of men- ingitis. 9. Epidemic cerebrospinal meningitis can be trans- mitted in utero. 21 BIBLIOGRAPHY. 1 Barker and F'lexner : Amer.Jonr. Med. Sci.. 1894. 2 Jaeger : Zeitschrift f. Hyg. u. Inf. Krankheiten. Leipzig, 1895. 3 Councilman, Mallory ancl Wright: Amer. Jour. Med. Set., March, 1898. 4 Class : The Journal of the Amer. Med. Asso., March 25, April 1, April 8, 1899. 0 Vieussieu : Hufeland's Journal, Heft 2, 1805. 0 Weichselbaum : Fortschritte d. Med.. 1887. ‘Jaeger: Loc. cit. 8 Barker and Flexner : Johns Hopkins Hospital Bulletin. February, 1898. 9 Class : Loc. cit. 10 Report of Committee of American Bacteriologists to the Committee on the Pollution of Water Supplies of the American Public Health Association, submitted at the meeting of the Association at Philadelphia, September, 1897. 11 Councilman : Amer .Jour. Med. Sci., March, 1898. Johns Hopkins Hospi- tal Bulletin. February, 1895. 12 Ghon : S.'e reference 4. 13 Councilman : Amer. Jour. Med. Sci.. March, 1898. 14 Barker : Loc. cit. 15 Herrick : Medical News. May 13, 1899. 111 Netter : Soc. medicate des Hopitaux, July 22, 1898. 17 Herrick : Loc. cit. 18 Netter : Loc. cit. 19 Class : Loc. cit. THE Philadelphia JWedieal Journal (WEEKLY) Dr. George M. Gould, Editor. Published solely in the interest of the pro- fession and medical science. Absolutely free from influences of manufac- turing or publishing houses. No secret articles advertised under any con- ditions. Greater amount of medical literature for the money than given by any other medical journal. 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