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THE DIAGNOSTIC VALUE OF THE CHEMICAL AND BACTERIOLOGICAL EXAMINATION OF

CEREBROSPINAL FLUID.

BY ALFRED HAND, JR., M.D.,

Philadelphia.

The exact diagnosis of the different forms of meningitis is always important. With the introduction of a specific treatment for one of the forms, which as Pepper used to say "maims for life when it does not kill, as does no other disease, save possibly scarlet fever," the importance is greatly increased of arriving at an exact diagnosis as early as possible. Thanks to Quincke, lumbar puncture furnishes the means of making an exact diagnosis. But the Auid obtained by lumbar puncture must always be examined with great care in order to arrive at a correct interpretation. There may be said to be two main types of cerebrospinal fluid, one in which the interpretation is easy and the other in which it is difficult. It is easy when the fluid is typical of one or another form of meningitis, but in the majority of cases it requires a painstaking, careful examination. Typical specimens present well-marked contrasts. Thus, if the Auid from a case of meningitis shows a milky opalescence, which disappears as the fibrinnetwork forms, leaving a clear fluid which contains a great increase in the normal amount of albumin and with the presence of sugar but little if any below the normal percentage, the fibrin network also being found to contain mainly mononuclear leukocytes and tubercle bacilli, the diagnosis is clearly tuberculous meningitis. If the fluid is distinctly turbid, with sometimes a slight yellowish tint, and polynuclear leukocytes are found in abundance some of them containing in their protoplasm diplococci, the diagnosis is established of epidemic cerebrospinal fever; after the fibrin network has formed and been withdrawn, further study of the fluid will show moderate increase in the albumin and total absence of sugar. A pneumococcic meningitis gives a very similar fluid, with occasionally a greenish-yellow tint, as in strepto- or staphylococcic meningitis, but the diplococcus in this form is hardly ever seen in the pus cells, being very abundant in the fluid. (In the two latest cases of pneumococcic meningitis which I have seen, the fluid from one secondary to an otitis had a few leukocytes which contained diplococci, while the majority of the germs were free in the fluid, and the fluid from the other, secondary to a small pneumonic focus, showed every polynuclear leukocyte surrounded by a complete ring of diplococci but none in the protoplasm). The fluid in this and other septic forms resembles that in the epidemic form in having a moderate increase in albumin and a total absence of sugar.

But the fluid obtained by lumbar puncture may not have these striking characteristics; it may be only slightly turbid or apparently perfectly clear, so that it is well to have a systematic method of examination. The first step of importance is to start the examination as soon after the fluid is obtained as possible. It is well to allow a drop to fall from the needle on to a slide; or shortly after collecting the fluid, a loopful is transferred to a slide, evaporated, and the film stained immediately. The meningococcus may then be found in great numbers in some cases, while an examination postponed over night may fail to show any germs whatever. Having taken this film and also cultures, which may also be made while the fluid is flowing from the needle, or soon after, the test tube containing the fluid is allowed to stand for several hours in order that the leukocytes and bacteria may sink and the fibrinnetwork form. Then with a straight platinum needle the network is carefully transferred to a slide, the best preparation being obtained by tilting the test tube so that the fibrin always floats in the fluid. It is then possible to spread out the network on the slide, evaporate the Auid and fix by heat. Before staining this preparation, it will save time to conduct a chemical examination of the fluid. Half of it may be used for a quantitative estimation of the albumin, and for this purpose the acetic acid and potassium ferrocyanid test in the graduated urine tubes and the centrifuge is convenient and seems to me to be reasonably accurate. At least, I have always found a fairly constant result for the different forms of meningitis. This test gives the bulk percentage of albumin, and every specimen of tuberculous meningitis I have examined has shown 5 per cent. or over, the usual amount being about 9 per cent. or 10 per cent. The other forms of meningitis have never exceeded 5 per cent. in my experience, the average being 3 per cent. or 4 per cent., the amount in normal fluid being one-half of i per cent.

The other half of the fluid should be used for the phenylhydrazin test for sugar; Fehling's solution may be used, but there is often not enough fluid to give a reaction, and the phenylhydrazin test is much more delicate.

The results of these two tests will serve as a guide for staining the slide previously prepared. If the albumin is above 5 per cent. by bulk and if sugar is present, then the staining should be for tubercle bacilli, with a mechanical stage used for the search, which will be rewarded with a positive result in something over 99 per cent. if the technic has been carefully followed.

If the albumin is below 5 per cent. and sugar is absent, it is hardly worth while to stain for tubercle bacilli, but the examination may then be devoted to a search for the meningococcus. It is sometimes impossible to decide whether a case is of the epidemic or pneumococcic variety, as the slide may show only a few isolated cocci, or even none at all.

I have thus far laid little stress on a differential count of the leukocytes; this is often of great value, when it can be made, but the cells are often distorted or degenerated and it is difficult in some cases to decide their true form.

The fact that the tuberculous form is associated with the persistence of sugar in the fluid and the almost total absence of polynuclear leukocytes, while the reverse holds for other infections led me to think that perhaps there was some relation between the two and that inasmuch as a proteolytic ferment has been obtained from degenerating leukocytes there might perhaps be also a sugar-splitting ferment. The experiments which I made are incomplete as yet, owing to a lack of coincidence of suitable material, but a preliminary report follows.

Pus from an empyema was used, giving no reduction of Fehling's solution.

One drop of pus from each c.c. was added to a 0.5 per cent. solution of glucose, giving a fluid of about the degree of turbidity of a pneumococcic meningitis, and the mixture was incubated for twenty-four hours at 37.5° C; at the end of that time the sugar was reduced exactly one-half, to 0.25 per cent.

Cultures of the pus on agar and blood-serum gave staphylococci. Another tube containing 0.5 per cent. glucose solution was inoculated with the germs and incubated for thirty-two hours, with an almost imperceptible lessening in the amount of sugar, the resulting calculation giving 0.49 per cent.

These results, if confirmed by subsequent tests, point to the existence of a sugar-splitting ferment in polynuclear leukocytes.

(Since writing the above, I have had an opportunity to use Flexner's antiserum in a case of meningococcic meningitis, the resulting changes in the characteristics of the fluid being extremely interesting. At the first tapping 45 c.c. of turbid fluid literally spouted from the needle; sugar was absent, albumin was increased to 5 per cent. by bulk, many leukocytes were present, staining very poorly with the outlines of the cells and nuclei very indistinct, a few of them containing diplococci. Injections of antiserum were given on the three days following, the fluid at the second and third tappings resembling that at the first, with 45 c.c. each time; at the fourth tapping, when the last dose of antiserum was given, only 15 c.c. were obtained, the albumin being slightly increased to 6 per cent., the leukocytes being well-preserved, polynuclears being in the majority but mononuclears being abundant, a few diplococci being found; and sugar was also present, probably an indication of a return to the normal condition of the Auid, as no further tappings were necessary, recovery being speedy).

THE SERUM TREATMENT AND THE PROGNOSIS, UNDER VARIOUS FORMS OF

FORMS OF THERAPY, OF CEREBROSPINAL FEVER.

BY HENRY KOPLIK, M.D.,

New York.

It is too often apparent in considering the methods of therapy of any disease that we sometimes lose sight in the presence of some exceedingly favorable results of the natural course of the affection, and in no disease is this more common than in cerebrospinal meningitis. This disease, as Osler has pointed out, resembles very closely in its behavior pneumonia. It is true the affection occurs sporadically and in epidemics. In the sporadic form the disease occurs at times when there cannot be said to be any prevalent epidemic. That is, a limited number of cases will appear in a city in places removed from each other, and having no connection with each other. By epidemics of meningitis we understand distinctly the occurrence in larger numbers of cases in groups, and in this disease, especially in densely populated quarters. In the sporadic form cerebrospinal fever is an affection at times so mild as to give few symptoms of a critical nature. At other times in the sporadic form the disease takes on a severer type, and then the picture closely resembles what is seen in epidemics of the disease. In the absence of epidemics the cases of cerebrospinal meningitis which have come under our control have impressed us with certain characteristics, or, rather, the absence of certain characteristics which we see during the times of epidemies. I have seen sporadic cases so mild that the intermittent or remittent febrile symptoms, headache and drowsiness, were the only symptoms which led us to think of the diagnosis. In the sporadic forms we have the rigidity, the hyperesthesia, the presence of the Kernig reaction, and in occasional cases the herpes. There is also delirium and the presence of gradually increasing hydrocephalus, as evinced by the so-called Macewen sign. I think any one who has passed through an epidemic of cerebrospinal meningitis will admit that in the sporadic cases

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