KOCH's figures were obtained from the brain of an epileptic. The analysis was conducted with great care and with the aid of more recent and accurate methods.

The wide differences in the figures of these two investigators show how far we are from establishing a comple quantitative composition for the normal human brain. Such figures can only be obtained as the average of a large number of analyses, and they must be firmly established and fully available before we can hope to make any comparison with pathological brain material.

The recent studies that have been made on pathological brains and cords, have related mainly to diseases where there is extensive general or focal destruction of nerve tissue, as in general paralysis and hemiplegia, comparisons with microscopical findings being made at the same time. W. BARRETT, as the result of the analyses of the brains and cords in general paralysis, found an invariable increase in

the water, while phosphorus was always slightly decreased, but this decrease seemed to bear no relation to the extent of fiber degeneration or cell chromatolysis. NOLL, in an experimentally degenerated sciatic nerve, found a decrease of phosphorus and of the alcoholic extract. CORIAT found cholin in the peripheral nerves, brain and cord of a case of alcoholic polyneuritis, the amounts being parallel to the extent of the MARCHI reaction. The presence of the alkaloid here must be looked upon as the result of autolytic processes in the lecithin.

MOTT and BARRETT, as the result of analysis of two cords from cases of hemiplegia, concluded, (1) that on the degenerated side of the cord a breaking up of the phosphorized fat occurs, (2) the amount of lecithin present is diminished, (3) fat is present in excess, (4) the amount of extractives soluble in ether is increased, (5) the proteid residue is diminished, (6) the phosphorus is diminished, (7) the ether extract has a buttery appearance instead of being crystalline. HALLIBURTON has shown that the cause of death from hyperpyrexia is a physico-chemical one, being due to the coagulation of the cell-globulin, and when this constituent of cell protoplasm is coagulated, the protoplasm as such is destroyed. The temperature for this reaction is 47° C, but temperatures as low as 42° C will have the same effect if continued sufficiently long.

So far there have been published only two studies on the important question of the autolysis of brain tissue, those of LEVENE and CORIAT. The former established the presence of an intracellular proteolytic enzyme in fresh brain tissue, and which acted only in an acid medium. CORIAT, working from the standpoint of the genesis of cholin in the central nervous system, on account of its importance as a toxic agent in producing the convulsive seizures of epilepsy and general paralysis, concluded that there exists in the brain an enzyme capable of splitting lecithin into glycero-phosphoric acid, stearic acid and cholin, the latter being detected and quantitated by means of its platinum compound. This enzyme acted only in neutral and slightly alkaline media, and like all enzymes it could be destroyed by heat.

HATAI, in studying the effects of starvation on the brains of white rats, found that the absolute weight in his starved groups was diminished, and there was an actual diminution of the water and an increase in the relative amount of extractives, from which he infers that the protein substance must have been mostly affected. It was therefore expected that changes in the cell bodies would be found, but no marked alteration of the NISSL bodies could be demonstrated. The same writer, as the result of injection and feeding experiments with

lecithin on white rats, to show its effect upon their growth, concludes as follows: White rats which received the lecithin either by injection or feeding, gained in body weight more rapidly than those which did not receive it, the gain in the experimented rats being on the average 60% greater than in the controls. The relative weight of the central nervous system in the lecithin rats was normal and contained the same proportion of water and solids as in the controls, this being another indication of the normal character of the growth The peripheral nerves in both groups also grew normally, as shown by the relative area of the axis cylinder to its sheath. The action of the lecithin appeared to be that of a stimulating agent for normal growth, and the rats which received it showed a greater power of resistance to unfavorable changes in their surroundings.

KOCH's work on the action of electrolytes on colloidal solutions of kephalin and lecithin is also of interest, as showing the possibilities of the study of metallic poisons on the various constituents of the central nervous system, from the standpoint of physical chemistry. These colloidal solutions, which form perhaps the nearest artificial approach to the substratum of the living cell, are precipitated by divalent kations, while precipitation is prevented by univalent and trivalent ones.

The most important constituent of the individual cell is the NISSL bodies, which consist principally of nucleic acid. This acid is not found pure, but in combination with proteids forming nucleo-proteids which are probably the most complex bodies in a living organism. These compounds have the property of acids, contain phosphorus and iron and also the purin and pyrimidin bases. There is also a carbohydrate, the exact nature of which is unknown, but which gives the furfurol reaction and probably belongs to the pentose group. The purin bases of cerebronucleo-proteid are adenin and guanin, and the pyrimidin bases, according to LEVENE, thymin and cytosin. The amount of phosphorus is lower than in the nucleo-proteids from other tissues. Under pathological conditions, especially in general paralysis, this nucleo-proteid passes into the cerebro-spinal fluid; the proteid in the normal fluid consists almost entirely of serum-globulin, nucleo-proteid being completely absent.

During the last few years the cerebro-spinal fluid has called forth an immense literature, partly because it may contain the products of nerve degeneration (cholin, glycerophosphoric and lactic acids, lecithin ?), and partly because in conditions of acute or chronic inflammatory processes in the brain, certain cells may appear in the fluid, the finding of which is a valuable diagnostic aid. The chromo- and cyto-diagno

sis of the fluid do not concern us here. The chemistry of the fluid will be touched upon, only so far as it relates to the products of myelin decay. The physical chemistry of the fluid (freezing point, etc.), the various proteids and the reducing body are all of interest, but their consideration would exceed the scope of this review.

The most important chemical substance which passes into the cerebrospinal fluid is cholin, which is the nitrogen-containing methyl group of lecithin, and can be looked upon as one of its autolytic decomposition products. In the normal fluid it is found in mere traces, but in the fluid from cases of general paralysis, as first shown by MOTT and HALLIBURTON, large amounts are present. Since HALLIBURTON first demonstrated cholin in general paralysis, in his Croonian lectures on the chemical side of nervous activity, it has been found in a multitude of other pathological conditions, but principally where recent and active nerve degeneration is taking place. The lecithin of the myelin sheaths of nerves, is decomposed, probably through the agency of some enzyme, into glycerophosphoric acid, stearic acid, and cholin. This latter is found in the blood and cerebro-spinal fluid, while it is absent from the urine, except in experiments on animals, where the alkaloid is given subcutaneously or intracerebrally. When cholin appears in the fluid, there is also an increase of phosphoric acid therein (DONATH), this being another proof of its derivation from lecithin. In long continued activity of the central nervous system, as in convulsive seizures, lactic acid in large quantities appears in the cerebro-spinal fluid.

Cholin is detected by means of its platinum combination, with which it forms a double salt, and crystallizes in single large yellow octahedral and occasionally twin crystals, and easily differentiated from the platinum salts of neurin and potassium, by reason of its solubility, percentage of platinum and large size and grouping of the crystals. Since HALLIBURTON first pointed out its occurrence in general paralysis, the work has been further elaborated by MOTT, WILSON, DONATH and CORIAT. As a result it is found in many pathological states, where there is an axonal reaction with corresponding fiber degeneration (central neuritis), general paralysis, brain tumor, tabes, HUNTINGTON'S chorea, delirium tremens, polyneuritis, epilepsy, senile dementia (especially where there is great wasting of the cortex), cerebral hemorrhage, beri-beri, POTT's disease, disseminated sclerosis, amyotrophic lateral sclerosis, focal myelitis, organic dementia, brain syphilis, chronic hydrocephalus (?) spina-bifida, neurasthenia (?) and hystero-epilepsy. It has also been found in the blood of animals after experimental sec

tion of the sciatic nerve, and in the peripheral nerves, brain and cord in polyneuritis and in all these latter, the amount present was parallel with the extent of the MARCHI reaction. This is easily explained if we remember that the MARCHI reaction depends on the preciptation of metallic osmium by stearic and oleic acids which are decomposition products of lecithin. The action of cholin on blood pressure has been carefully studied by MOTT and HALLIBURTON, while DONATH has shown that the injection or intracerebral application of cholin produces in animals, strong convulsive phenomena, and he concludes from these experiments that the seizures in general paralysis and epilepsy are due to intoxication by this alkaloid.

In closing, we should like to say a few words on DONATH's latest, and in many respects, his most pretentious paper, on the significance of cholin in epilepsy. He examined for cholin in sixty-four cases, detecting it by means of the platinum compound. In addition to the organic cases, where its presence would be expected, he finds it in those which we look upon as being functional in nature (neurasthenia). In addition, he finds the myelin forms of lecithin in two of his cases. This seems to us extremely doubtful and altogether inexplicable. Although using the platinum compound as a means of detecting cholin, yet according to the drawings and photomicrographs appended to his paper, he does not confine himself to octahedral or hexagonal crystals for a positive reaction, but labels anything and everything of crystalline nature as "cholin," while we have always hesitated, and then put down as negative, what DONATH in a large number of cases calls a positive cholin finding.

The bibliography appended makes no claim to completeness; it merely gives those papers directly mentioned in this review, or those which have been consulted for the discussion of the material.