extension may be direct or by means of lymphatics which communicate with those of the membrane.

All inflammatory processes in the pia arachnoid, however produced, agree more or less in their anatomic features. There are, however, certain minor differences in anatomic lesions which are sufficient to differentiate certain forms of meningitis from others In certain cases these differences are more accentuated than they are in others. The same character of exudation may be produced by the diplococcus intracellularis meningitidis, by the pneumococcus, and by the streptococcus. Even cases of tuberculous meningitis may be found in which there may be a fibrino-purulent exudation without the presence of tubercles. The differences lie mainly in the extent and character of the involvement of the brain, and in the degree to which the intima of the veins and arteries is affected. It would be possible anatomically to distinguish cases of acute epidemic cerebrospinal meningitis from other forms, but the differentiation could not be carried further. All cases of meningitis are cerebrospinal, the meninges of the cord being affected as well as those of the brain. In certain forms, the cord lesions are more marked.

Acute meningitis may be produced by a number of bacteria, but chiefly by those belonging to the pyogenic organisms. The three organisms most generally concerned are the diplococcus intracellularis meningitidis, pneumococcus, and the streptococcus. Of these, the first named deserves the most attention in that it is the cause of the epidemic form of the disease. This organism was first described by Weichselbaum, in 1887, as a specific micrococcus resembling the gonococcus. He found it in six cases of acute cerebrospinal meningitis. The work was confirmed by several investigators, and in 1895, Jager found it in a small epidemic which prevailed in the garrison at Stuttgart. To Jager belongs the credit of first recognizing this organisin as the cause of epidemic cerebrospinal meningitis. The description which Jager gave of the organism differs in minor details from that given by Weichselbaum. Weichselbaum has never regarded it as the sole cause of epidemic meningitis but considers that epidemics also may be caused by the pneumococcus. In the very considerable epidemic which prevailed in Massachusetts in 1897, and which was reported by Councilman, Mallory and Wright, this diplococcus was established as the only cause. It was found in thirty-one of the thirty-five cases which came to autopsy. Lumbar puncture was performed in fifty-five cases, and in thirty-eight of these the same organism was found. It was present in all of the acute cases, but rarely in those which ran a more chronic course. Thus, in lumbar puncture, the average duration from the onset of disease until the puncture was seven days in the cases in which the organism was found, and seventeen days in the negative cases.

The organism is one which is cultivated with difficulty. Morphologically, the organisms appear as diplococci occurring as paired

hemispheres, separated by well-marked, unstained intervals, and showing in cultures considerable variations in size. There is a tendency to grouping in fours, or tetrads. In cover-glass preparations from the meningeal exudate, the diplococcus is frequently situated inside leucocytes and sometimes within the nucleus. The appearance is very much like that of gonorrheal pus. The organisı n is discolorized by the Gram method of staining; in cultures it grows best on blood serum. The colonies are round, colorless, slightly convex or flat, moist and viscid-looking; they may become confluent. The organism has feeble vitality and dies out quickly under cultivation. It has a weak pathogenesis for laboratory animals. The cultures vary in virulence in certain cases, 1 c.c. of a bouillon suspension of a twenty-four-hour blood serum collected and injected intraperitoneally in a guinea-pig will kill the animal in forty-eight hours.*

This type of meningitis is constantly present; it exists in th form of epidemics, which are repeated with some regularity. The disease has peculiar interest in Massachusetts from the fact that it was first described here by Danielsen and Mann, in 1806. There have been four epidemics in the State, each of which has been mad e the subject of a special report. These epidemics occurred in 180, 1864, 1874 and 1897. There is a great difference in the morbidit and mortality of the disease in the different epidemics; Hirse h places the mortality at from 20 to 75 per cent. In the last epidemic, in Boston, the mortality was 65 per cent.; the epidemics are usuall of short duration. Between the epidemics, sporadic cases appea which may be more numerous in some years than in others. Before careful bacteriologic examinations rendered the recognition of the disease certain, the character of the infection in sporadic cases was determined by the clinical history, with or without the reports o autopsies. The disease is sufficiently characteristic to make this method approximately correct. In 1897, from the clinical reports, in some cases with autopsies, it seemed probable that here and i Europe sporadic cases were common. The main clinical features distinguishing sporadic cases of epidemic cerebrospinal meningitīs from other forms of meningitis were the low mortality (in twenty four cases from the clinic of Professor Bauer, reported in 1890, there were eight deaths, and in seventeen cases reported from Ziemssen's clinic at the same time there were three deaths), its appearance as a primary affection, and the frequency with which it is followed by secondary affections of the eye and ear.

f

Since our study of the disease in 1897 there have been numerous reports of sporadic cases, in which careful bacteriologic study of the exudation have determined in the presence of the diplococcus intracellularis meningitidis, and have confirmed the conclusions which we reached in 1897 of the frequency of sporadic cases. Since 1898 there have been sixty-one autopsies on meningitis at the Boston City and Massachusetts General Hospitals, with bacterio

* Mallory and Wright: Pathological Technic, 1904.

logic study of the exudation. In thirteen of these the diplococcus intracellularis meningitidis was found in culture. In addition to these there were eight cases which were considered due to the same cause but in which the organism was not obtained in cultures. Of these five were chronic, with organization of exudation, the organism having evidently died out, and in three the cultures were negative from unknown causes. All of these were primary and did not differ from the type of disease which we had studied in the epidemic in 1897. The absence of bacteria in carefully made cultures of the exudation in acute primary meningitis speaks in favor of this type, for the diplococcus is rather difficult to cultivate, of feeble vitality and can easily die out.

These statistics give no idea of the frequency of the disease. We know that cases do recover, for there are numerous reports of recovery of cases in which the diplococcus has been found in the fluid from spinal puncture, There is great need of more accurate statistics on this subject, and these are to be obtained by careful bacteriologic examination of fluid derived from spinal puncture, in large number of cases, including those in which the disease may only be suspected.

Examination of the health statistics in Massachusetts shows a gradual decline in the number of deaths from epidemic cerebrospinal meningitis from 1897 to 1902. In 1897, which was the chief year of the epidemic, there were 355 cases. The deaths were most numerous in April, May and June, which are the months in which the epidemics are most fatal. In 1898 there were 259 cases, the epidemic influence being slightly shown by ninety-one cases in the same months. In 1899 there were 240 cases; in 1900, 165; in 1901, 176, and in 1902, 165 cases. These cases were scattered over the State without occurring in sufficient numbers in any one place to constitute an epidemic. There is no way of positively determining whether or not they were due to the diplococcus intracellularis. In the Massachusetts reports, other forms of meningitis were placed under the head of cephalitis until 1901, when the term "other forms of meningitis was used. In 1900 there were 1,205 cases of cerebritis; in 1901, 1,168 cases of other forms of meningitis, and in 1902, 1,200 cases. The cases described as cerebrospinal meningitis are the primary cases, the secondary cases coming under other forms. It is, of course, difficult to determine, without an autopsy account, whether meningitis is or is not primary. All my experience leads me to the belief that, with rare exceptions, cases of primary meningitis are due to the diplococcus intracellularis. In the thirty-five autopsies made in 1897, all the cases were primary, and the twentyone found since were also primary. In the remaining forty of the fifty-eight cases only two, in one of which the pneumococcus was found and in one the streptococcus, were regarded as primary. It can be concluded, both from autopsy evidence and from statistics, that sporadic cases of meningitis due to diplococcus intracellularis are of frequent occurrence, but we have no way of determining how

frequent the disease is. Autopsy experience shows that the disease is more frequently not diagnosed when present than the reverse. We have no means of estimating the mortality of meningitis due to the pneumococcus or streptococcus; these cases are usually secondary, and the mortality in secondary meningitis is much higher than in the primary form. Up to 1898 we could not find a case in which the culture of fluid from spinal puncture showecl pneumococci or streptococci in which recovery took place. Since 1898 there have been, at the Boston City Hospital, four lumba r punctures in which the pneumococcus was found and three in which the streptococcus was found, all of which cases resulted fatally-. To a certain extent we can judge of the frequency of the disease by evidences at autopsies preceding inflammation of the pia arachnoid, shown by thickening due to connective tissue increase and by lymphocyte infiltration with a corresponding increase in the glia of the cortex, and glia thickening and granulations on th surface of the ventricles. This condition, which is not uncommon can be the result of a preceding acute infection, but certainly no₺ all cases are the result of this.

The presence of these sporadic cases is of importance in the occurrence of epidemics. The diplococcus intracellularis is an organism of feeble vitality; it dies out easily on exposure to drying and light and is incapable of a saprophytic existence. In the absence of intervening infections, it would be impossible for the period of epidemics to be bridged over. Not only this, but there is evidence that this organism can produce other infection S and may even live as an inhabitant on the normal mucous mem brane. There have been a great many cases reported of the presence of the diplococcus intracellularis meningitidis in the

In most of these the diagnosis was made on morphologic grounds, and such cases should be thrown out, owing to the probability that the organism was confounded with the micrococcus catarrhalis, which it resembles in morphology and in staining reaction. The differential diagnosis can only be made in cultures. In fifteen cases of meningitis examined in the Boston epidemic, diplococci decolorized by Gram were found in ten. In twelve cases, chosen at random, similar diplococci were found in two. Attempts were made to cultivate the organisms, but not successfully.

Lord has examined the bacteria of the nose in twenty-one cases. In the nose of a physician who had been in daily attend ance in the throat room and who had a severe rhinitis with congestion of the mucous membrane and profuse muco-purulent discharge, he found diplococci which all tests showed to be the meningitidis. In reviewing the literature, Lord accepts but three cases, making, with his own, four, in which the diplococcus intracellularis has certainly been found in the nose. Some of these cases are of considerable interest. Kiefer, after experimenting for some days with the cultivation of the organism with the view of

comparing it with the gonococcus, suddenly acquired a severe purulent rhinitis, with headache, nervousness and an uncomfortable sense of contraction of the neck. The temperature remained normal. Examination of the nasal pus by cultures demonstrated the presence of the diplococcus intracellularis, along with other bacteria the rhinitis lasted fourteen days. In this case it seemed probable that there was a primary infection of the nose, with a slight meningitis, resulting from extension of the infection through the lymphatics into the meninges. The case lacks the proof which spinal puncture should have given, both of the meningitis and of the character of the meningeal infection, if present. There can be no doubt that extension may take place from the meninges into the nose, just as it does into the ears and eyes. Rhinitis is not an uncommon condition in acute meningitis, and Albrecht and Ghon found the diplococcus intracellularis by culture from the nose in one of their cases of acute meningitis. The evidence which we have justifies us in the conclusion that there is a form of meningitis produced by the diplococcus intracellularis meningitidis, that the epidemics of acute meningitis are due to this organism, that sporadic cases are not infrequent, that, with rare exceptions, primary cases of meningitis are due to this organism; that recovery takes place much more frequently in this type of disease than when infection is due either to the pneumococcus or the streptococcus, that the disease is more common than is generally supposed, that the organism does not live as a saprophyte outside the body, that the organism may be found on the mucous membrane of the nose, where it may produce a rhinitis, and that it is probable that infection of the meninges takes place by extension from some of the adjacent mucous membranes by means of the lymphatics. We can only explain the epidemics of the disease by the assumption that at certain times the power of infection is increased either by an increase in the virulence of the diplococcus or by a decrease in the resistance of the tissues. The study of the influenza bacillus in the past years has shown' much the same condition. The organism is constantly present, and not only are sporadic infections produced by it frequent, but the bacillus may live as a harmless inhabitant of a mucous surface. The causes underlying the occurrence of epidemics are unknown, and even atmospheric conditions can not be excluded. With regard to the pneumococcus, we know that the organism is associated with acute croupous pneumonia, but we do not know the underlying conditions which enable the pneumococcus to produce this disease.

Of the sixty-one cases of sporadic meningitis seen since 1897, eighteen were found to be due to the pneumococcus. Weichselbaum regards this organisin as one of the most frequent excitors of both primary and secondary meningitis, and both he and Netter believe that meningitis due to pneumococcus may appear in epidemic form. In the report on meningitis in 1898, ten cases were found to be due to the pneumococcus, and in two of these