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extremities, while in myoclonia the limbs are more commonly affected than the face. While chorea is commonly unilateral, myoclonia is usually bilateral, voluntary movements are apt to evoke chorea, but retard the movements in myoclonia. Then, too, there is a marked difference in the apparently purposive irregular arythmic group-like contractions of the muscles in chorea, and the shock-like contractions in myoclonia.
The patient has improved very much under the use of thyroid tablets, so that pressure on the muscles or nerves and tapping the tendons does not now produce the muscular phenomena after three weeks treatment.
RECENT STUDIES IN RABIES.
BY JAS. N. BRAWNER, M.D., ATLANTA.
Since Pasteur's memorable work on rabies, demonstrating the constant occurrence of the virus in the nervous system and the means of attenuating it so that preventive inoculations might be made, numerous investigators have studied this disease in every detail. Especial attention has been paid to the pathology and every portion of the nervous system has been minutely scrutinized by the best histologists in search of specific lesions. Other workers have been especially active in trying to improve on the preventive inoculations of Pasteur or to get an effective serum. One or two have been equally active in trying to disprove the existence of such a disease communicable to man, and have written many articles setting forth their claims. Those who deny the existence of rabies are fast disappearing, and it is now rare to see a physician skeptical on the subject.
While an immense amount of work has been done to improve on the preventive treatment now used at all the Pasteur institutes, but little has been accomplished. Various means have been used to attenuate the virus and many attempts have been made to obtain a serum that would be effective after symptoms develop, but practically no improvements have been made on the method of treatment first demonstrated by Pasteur, excepting, perhaps, that much larger doses than formerly are now used.
The pathology of rabies is interesting from many standpoints, and important results have been obtained from recent investigations along this line. One of the most practical questions has been, can a specific lesion or micro-organism be found so that a rapid and positive diagnosis may be made from a microscopical examination of the tissues. The lack of a means for rapid diagnosis in cases of suspected rabies in animals has been long felt, as patients are often put to unnecessary worry and delay awaiting the result of the inoculation of rabbits.
It is not necessary to describe the "rabic tubercle" of Babes, or the epitheloid infiltrations about the neurons, first mentioned by Van Gehutchten and Nelis; but we will consider more in detail those structures more recently described, now commonly known as "Negri bodies."
In March, 1903, Dr. A. Negri, of the University of Pavia, announced the discovery of certain bodies in the central nervous system of animals dead of rabies which he believed to be the specific germ of this disease. This announcement, coming from Dr. Golgi's assistant, and one perfectly familiar with the microscopical appearance of both normal and pathologic nerve tissue, at once attracted attention. Since that time numerous investigators, especially the Italians, have confirmed his results.
In August, 1903, Dr. Negri made a further report, stating to that time he had examined the nervous systems of over one hundred animals suffering from rabies and various other diseases, and found the bodies only in the animals proven to be rabid by the inoculation test. In two instances where rabies existed the structures could not be demonstrated.
Later, Bertarelli and Volpino found the bodies described by Negri in the brain of a boy who died of hydrophobia. Bertarelli, summarizing the work done in
Italy by Negri, Volpino, Abba, Bermans and himself, states that in more than a thousand tests the bodies were found in all cases of rabies except three, and were never found in animals free from the disease, as determined by the inoculation of rabbits.
Poor, in New York, after twenty-three examinations, confirmed the results of the Italians.
The structures described by Negri are usually found in the cytoplasm of nerve cells or the proximal ends of their processes, but not in the nucleus, though they may be in contact with it. He believes them to be protozoa. They occur most frequently as inclusions of the large pyramidal cells of the hippocampus major, Purkinje cells of the cerebellum, the large cells of the spinal ganglia, spinal cord, pons and occasionally the pyramidal cells of the cerebral cortex. As a rule they are much more numerous in the hippocampus major than in other portions of the nervous system, though this is not always the case, as they may be absent here and numerous in the spinal cord or cerebellum. Negri states that when rabies is produced by inoculation into the sciatic nerve the bodies are found chiefly in the spinal cord and ganglia, rarely in the brain. When the inoculation is on the face, they are more abundant in the gasserian ganglia, hippocampus major and cerebellum. There seems to be a difference of symptoms corresponding to the distribution of the bodies. Ordinarily when the disease is acquired in the natural manner they are larger and more numerous in the hippocampus major. This is probably due to the fact that most bites communicating the disease are inflicted on the head or face.
As usually found, Negri bodies are from four to six microns in diameter. Occasionally, especially early in the disease, they are very small, barely visible with a
1-12 oil immersion. At other times they are large, measuring twenty-five microns in length. The larger forms are more frequently found in laboratory rabies and in the natural form closest to the site of inoculation.
They are round or oval in shape, occasionally irregular or elongated. When seen in fresh, unstained tissue, teased in a dilute acetic acid solution, they seem to consist of a nongranulated substance of hyaline appearance. In the center of the larger forms bright spots may be seen, surrounded by a band of homogeneous protoplasm. In specimens stained with eosin and methylene blue, they appear as dark red structures imbedded in the blue protoplasm of the nerve cells. They show up black in specimens stained with osmic acid.
To demonstrate these bodies, fix a small piece of each the hippocampus major and cerebellum in a saturated solution of corrosive sublimate, or of Zenker's fluid, dehydrate in absolute alcohol for six or eight hours, and section in paraffin. The sections should be thin and uniform. Fix upon a slide with Mayer's albumen, treat with a one-half per cent. aqueous solution of eosin for five minutes, wash in water and counter stain with a onehalf per cent. aqueous solution of methylene blue for five minutes. Rinse in water, dehydrate absolute alcohol, clear in xylol and mount in balsam. In specimens thus prepared, the Negri bodies stand out very distinctly as dark red structures, imbedded in the blue cytoplasm of nerve cells. As a rule, but one body is found in a cell, though occasionally two, three or even four may be found. The smaller bodies appear homogeneous in structure, but the larger ones contain a blue central mass resembling a nucleus. (Demonstration.)
While most observers believe these bodies to be the causative factor in rabies, all admit that posi