its use appears to produce in individual cases. It so modifies and changes the course of the disease as to present a very sharp contrast with the course usually seen in cerebrospinal meningitis treated by other methods.

The three principal effects of the use of the serum seem to be: First, to produce a fall of temperature; second, to produce a rapid improvement in the patient's general condition, accompanied by a more or less marked relief of certain symptoms; and, third, to cut short the course of the disease.

The most striking effect on the temperature is a permanent critical fall following the first dose of serum. Other cases showed a similar critical fall of temperature, which was, however, not permanent, the temperature rising again and finally coming down by lysis. Another effect was seen in a rapid permanent lysis, which was very striking in cases in which there had been a consistent high temperature up to the time when the first dose of serum was given. In other cases temporary relapses occurred, and in some there was no immediate effect.

The effect on the symptoms and general condition is the most striking phenomenon observed with the use of the serum. In some cases there occurred a permanent return to consciousness, a disappearance of mental dullness, a disappearance of delirium, and a disappearance of headache, hyperesthesia, tenderness of the neck or vomiting. These symptoms were often relieved completely within twenty-four hours after the first injection, the patient changing in the most remarkable way from a serious condition of coma to a favorable condition of normal mental activity.

At other times the improvement in this set of symptoms occurred more slowly, and at still other times, particularly in the late clironic cases, no such effect was noted.

As to the cutting short of the disease, the average length of time which patients remained under treatment was but a small fraction of the time which patients who recovered, remained under treatment at the hospital in previous years.

Another notable effect of the serum is seen in the successive examinations of the cerebrospinal fluid during the period of its use. This effect is most striking in early cases, in which the cerebrospinal fluid contains large numbers of diplococci. In such a case a great many intracellular diplococci are observed in the fluid withdrawn by the first lumbar puncture. Twenty-four hours after the first injection the fluid presents a strikingly different picture. The whole number of organisms seen is much smaller, but the chief change is that the majority are intracellular, only rare extracellular forms being seen. The third lumbar puncture shows still fewer diplococci, and those only intracellular. In the fourth fluid, after three doses, there are frequently no diplococci to be found, or, at most, very rare intracellular forms.

Relapses sometimes occur under the use of the serum. In a relapse, after a period of improvement, the symptoms begin to recur and the temperature to rise. These relapses usually yielded to repeated doses of antiserum.

The completeness of recovery is another noteworthy point in this series. There were sequelæ in 2 cases only, one child being deaf and one blind and deaf.

The results of the use of the serum appeared to depend chiefly on how early it was first used. The earlier it was employed the more marked were its effects.

We may conclude that the prospects of aborting or rapidly cutting short epidemic cerebrospinal meningitis are better the earlier in the disease the serum is given, and that the antiserum usually has no effect in the late chronic stage. There were cases which proved exceptions to this rule, as in 3 cases in which the serum was used comparatively early the patients died. On the other hand, one patient in the late chronic stage began to improve immediately after one dose of serum and made a rapid convalescence. This would show that there is always some hope of a good result so long as diplococci are present. I believe the serum in most cases causes a cessation of the active process and that the resulting course of the disease depends mainly on the extent of tissue damage which has already been done.

As to the amount of serum which should be given, I believe that 30 c.c. can be given usually with perfect safety, even when smaller amounts of fluid are withdrawn. I have given, without any bad results, as much as this when no fuid was withdrawn. One can judge to a certain extent how far it is safe to go by the feeling of resistance to the injection of the serum. In cases in which larger amounts of Auid are withdrawn I believe 45 c.c. should be given at a dose.

The daily injection of the serum in most cases seemed to be effective. After four doses have been given, if, after one or two days the case proves resistant, or at any time if there is a tendency to relapse, this treatment should be repeated. It is a question whether in some severe cases the serum should not be administered oftener than once in twenty-four hours.

I conclude from this series that:

(1) The use of the Flexner antiserum is of great value in epidemic cerebrospinal meningitis. I believe its value to be comparable to that of diphtheria antitoxin in diphtheria.

(2) The use of the serum at times aborts the disease, frequently rapidly relieves its symptoms, shortens its course, lessens the liability to sequelæ, and greatly reduces its mortality.

(3) The serum should be used as early as possible in all cases, even of suspected epidemic meningitis.

(4) It should be frequently repeated as long as there are symptoms or any tendency to relapse.

(5) Late chronic cases are unfavorable for the use of the serum, but any case in which the diplococci are present has some hope of relief by its use.

(6) Some cases are resistant.



Instructor in Pediatrics in the Johns Hopkins Medical School.


Assistant in Medicine in the Johns Hopkins Medical School.

Introductory.-An increase in the cerebrospinal fluid in inflammation of the meninges has been recognized for many years. Judging, however, from the comparatively small number of cases reported, the definite association of hydrocephalus with cerebrospinal meningitis has not attracted wide attention. This is in part explained by the insidious onset which frequently characterizes hydrocephalus, masking its connection with an antecedent attack of meningitis. Moreover, an increase in intraventricular Auid when of moderate degree in an adult skull, which admits of no dilatation, produces a rather vague and uncertain train of symptoms and may so escape detection. However, in nearly all the text-books, cerebrospinal meningitis is set down among the several causes suggested for the remarkable condition, hydrocephalus, the pathology of which is still so unsettled.

Historical.Joslin, in a partial review of the history of internal hydrocephalus following cerebrospinal fever, finds that in the same year, 1805, in which epidemic cerebrospinal meningitis is considered to have appeared, a case occurred in Strasburg having typical symptoms, and which on autopsy besides the meningeal congestion and inflammation showed the ventricles to be dilated with turbid serum.

A good description of this complication appears in Foerster's text-book of "Pathological Anatomy,"? published in 1863. Two years later, Ziemsen and Hess3 especially directed attention to hydrocephalus during an epidemic of cerebrospinal meningitis in Erlange. They reported 4 cases with autopsies. Several additional instances have been published, among others, by Merkel, Niemeyer," Bohmer, Bonsaing,” Pimser,Collins, Hart,19 and von Hartung." The clinical symptoms and the pathological findings of the reported cases show striking similarity. After the acute symptoms of onset there may be marked improvement, which continues indefinitely, or may be interrupted by paroxysms of severe headache, pain in neck and extremities, vomiting, loss of consciousness or convulsions; often there is fever. These symptoms may subside and remain absent for long periods, during which the patient may appear quite well, although abnormalities in the power of concentration or in reflex reaction are usually present. In a number of cases there is no period of convalescence, the symptoms attributable to the hydrocephalus following immediately after those of the meningitis.

According to Ziemsen,u2 to whose description of the anatomical findings in 1874 little has been added, after the second or third week the meningeal exudate begins to break down and to be absorbed, and there is an increase in the connective tissue of the serous membranes. The hyperemia of the brain, which marks the acute stage, subsides. At the same time, usually in about the fifth to eighth week, the exudate in the ventricles becomes purulent. Still later there is hyperplasia of the ependyma, then often fibrous thickening. The ventricular exudate increases in amount, becomes clearer, the cellular contents tend to sink to the posterior horns. In many cases there is definite edema of the brain substance. The choroid plexus becomes blanched. The brain tissue softens, is continually pressed upon by the increasing fluid and gradually atrophies—it may be to a mere shell. Most of the cases prove fatal before these advanced changes take place. The inflammation appears to be carried to the ventricular ependyma along the course of the blood vessels, extending into the brain substance from the meninges. Merkel (loc. cit.) found an extensive cellular proliferation about the vessels of the ependyma and plexus. It is probable, too, that a venous stasis is partly brought about by increased intraventricular pressure, and so further infiltration of Auid is encouraged.

Hulsmann,13 who makes this condition the subject of his inaugural dissertation, reports a remarkable case, which shows how extensive the cerebral alterations may be without symptoms. The patient was a child of three years, who was suddenly seized

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