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 based on experience, that the syphilitic poison is the cause of these diseases in the majority of instances. Again, syphilis, when it attacks the supporting, enclosing and nutrient vascular tissues, shows a predilection to affect structures about the base of the brain, and paralyses of the third nerve are almost pathognomonic of this disease. In rabies, although the whole nervous system is charged with the poison, the medulla oblongata (as shown by the symptoms) is especially affected. Again, in tetanus the bacilli are only found in the wound; they must therefore be comparatively few in number, but they elaborate a virulent poison, which affects particular groups of neurones. The fact that lockjaw nearly always occurs first, shows that the poison selects the motor nucleus of the fifth nerve; but it is remarkable that experiment has shown that the tetanus toxin, if mixed with an emulsion of nervous matter before injection into an animal, loses its toxicity. This fact indicates its affinity for nervous matter, and also a power of absorption of the poison by some chemical substance in the nervous matter. Another example is offered by diphtheria. A neuro-toxin is produced by the local action of the bacilli, for they do not become freely generalized in the blood and tissues. Whether the poison is a direct production of the bacilli themselves, or is an auto-toxin created in the body itself, by an influence exerted on the living fluids and tissues by a ferment-like product of the bacilli, is not determined. But whatever may be the source of the toxin, its effects upon the neurones are constant, as shown by the sufferings of the patients—paralysis of the soft palate, with nasal speech and regurgitation of fluids through the nose when swallowing is attempted; inability to read, owing to the paralysis of the muscle of accommodation; weakness and inco-ordination of the limbs, which may amount to paralysis; absence of the knee-jerks; and often skin anaesthesia.

The relation of protozoa to the existence of widespread diseases affecting men and animals is becoming yearly of greater importance and interest. Certain hitherto obscure diseases in which the nervous system is profoundly affected are now explained by the invasion of the tissues of the body by these lowly organisms, for example,

Sleeping Sickness, the cause of which has been definitely proved to be the Trypanosoma gambiense (see Plate II. fig. 1.)

The discovery by Schaudinn of the presence of the Spirochaete Pallida (see Plate II. fig. 2) in the primary and secondary lesions of seventy successive cases of syphilis, and the general acceptance of this organism as the cause of the disease, taken together with the fact that in many respects it simulates the trypanosome in its mode of division and other characters, tend to prove that syphilis is also a protozoal disease.

The bacterial invasion of tissues is generally characterized by a migration of polymorpho-nuclear leucocytes, but protozoal invasion is characterized by a formative hyperplasia of the fixed cell tissues, endothelial, epithelial and conjunctival, and there is a close similarity in the defensive reaction of the tissues to all forms of protozoal invasion (see Plate II. with explanatory text).

If the cause of rabies be regarded as proved since the discovery of Negri bodies, we may assume that just as in malaria the Haematozoon malariae undergoes its endocellular development in the red blood corpuscle, the protozoon of rabies undergoes its endocellular development in the nerve cell.

Only a short time has elapsed since Negri showed that in cases of rabies, whether experimental or otherwise, curious bodies measuring from 1 to 20. could be constantly found in the nerve cells, and that these bodies are not found in the nerve cells in any other disease; so that even if the theory advanced that they are endocellular forms of protozoa prove not true, yet the discovery affords a valuable and expeditious means of determining whether a suspected animal suffered with rabies or not. It is known that the salivary glands and saliva contain the virus, even before the animal shows symptoms. It is known too that the central nervous system contains the virus and that it multiplies there. Experimental inoculation can be made either from the saliva or an emulsion of the central nervous system of an animal suffering with rabies. Moreover, the virus can pass through a Berkfeldt filter; and if the filtrable product be injected into an animal, the animal thus inoculated will die of rabies and exhibit the Negri bodies. There are only two conclusions to be drawn from these observations: (1) If it be a protozoal disease, the organism at one period of its developmental cycle must be so small as to be able to pass through the pores of the Berkfeldt filter. (2) Negri bodies are the result of intra-cellular degenerative changes caused by an elective affinity of the virus for the protoplasm of the nerve cell. The virus, whatever it may be, does not exist in the blood and other organs and tissues. Seeing that the Negri bodies cannot be found in the saliva, although the saliva contains the virus, nor can they be found in the peripheral nerves, although the virus passes by the lymphatics of the nerves to the nerve cells of the spinal ganglia and central nervous system, it must be concluded that the filtrable virus travels to the central nervous system and there increases.

It is a remarkable fact that before the discovery of the Negri bodies, the diagnosis of rabies was made by microscopic examination of the spinal and sympathetic ganglia, particularly the ganglia of the vagus and fifth nerves. Changes were found similar to those met with in other protozoal diseases, namely, sleeping sickness, dourine and syphilis. These changes were proliferation of the interstitial connective tissue cells forming the supporting structure of the ganglion and hyperplasia of the lymphatic endothelial cells forming the capsule containing the nerve cells.

The diagram here given (fig. 1) after Volpino explains the supposed developmental cycle of the protozoon which is presumed to be the cause of rabies. The weak link in the chain is the assumed sporozoit which is so small as to be capable of passing through a Berkfeldt filter. It has taken twenty years to lead to the complete knowledge of the life history of the malarial parasite and its relation to the disease, and all we can say is that there is now a certain amount of evidence forthcoming which tends to show that rabies is due to a protozoon, which Calkins, who discovered a similar body in the epithelial cells of variola, places among the rhizopods.

There are certain chronic trypanosome infections in which the nervous symptoms form a special feature of the disease, notably sleeping sickness (see Plate II. fig. 1) and a disease affecting horses, termed mal de coit or dourine.

The chronic trypanosome affections resemble in many respects syphilis; they are characterized by local infection, enlargement of the nearest lymphatic glands, a general polyadenitis and successive eruptions, accompanied by fever. The tissue changes are the same whether we examine the primary seat of infection, papular eruptions on the mucous membrane or the skin, or the lymphatic glands. When the nervous system is affected a local or general chronic meningo-encephalitis is set up, characterized by a meningeal and perivascular infiltration with lymphocytes and plasma cells, occasioned by a chronic irritative process, presumably caused in the case of sleeping sickness by the presence of trypanosomes in the cerebro-spinal fluid (see fig. 8, Plate II.). The same perivascular and meningeal infiltration with plasma cells and lymphocytes is found in syphilitic and parasyphilitic diseases of the nervous system (see Plate II., figs. 7 and 9).

The significance of pathological changes in the cerebro-spinal fluid has recently become of great importance in the diagnosis of nervous diseases, and a short account of the subject in this article will therefore not be out of place. The cerebro-spinal fluid is clear like water; it has a specific gravity of 1006 and resembles in its composition the blood minus its

corpuscular and albuminous constituents. It is secreted by the choroid plexus, and if any cause, such as tumour or meningitis, should interfere with its escape from the ventricles it gives rise by pressure to internal hydrocephalus and cerebral anaemia which may occasion epileptic convulsions and various degrees of drowsy stupor, lethargy, unconsciousness and even coma. Withdrawal of the fluid by lumbar puncture and by tapping the ventricles of the brain has been employed in treatment, but without very satisfactory results. If, however, lumbar puncture has proved of but little use in treatment, it has proved of inestimable service in the diagnosis of various diseases of the central nervous system. The fluid withdrawn may be examined in various ways which are complementary to one another.

It should be centrifuged and the deposit examined microscopically if necessary after staining by suitable methods; the existence of cells