648 DISEASES CAUSED BY FILTRABLE VIRUS 



may show a course of gradually increasing weakness and progressive 

 paralysis extending over a period of two weeks after the appearance of 

 the first symptoms. 



In man, the disease begins usually with headaches and nervous de- 

 pression. This is followed by difficulty in swallowing and spasms of the 

 respiratory muscles. These symptoms occur intermittently, the free 

 intervals being marked by attacks of terror and nervous depression. 

 Occasionally there are maniacal attacks in which the patient raves and 

 completely loses self-control. Finally, paralysis sets in, ending event- 

 ually in death. 



Pathological examination of the tissues of rabid animals and human 

 beings reveals macroscopically nothing but ecchymoses in some of 

 the mucous and serous membranes. Microscopically, however, many 

 abnormal changes have been observed and were formerly utilized in 

 histological diagnosis of the condition. Babes 1 has described a disap- 

 pearance of the chromatic element in the nerve cells of the spinal cord. 

 This observation has been confirmed by others, 2 but is no longer regarded 

 as pathognomonic of rabies. The same observer has described a 

 marked leucocytic infiltration which occurs about the blood-vessels of 

 the brain and about the ganglia of the sympathetic system. These 

 changes are not found in animals infected with virus fixe and are present 

 only in animals and human beings inoculated with street virus. 



In 1903, Negri 3 of Pa via described peculiar structures which he 

 observed in the cells of the central nervous system of -rabid dogs. While 

 present in all parts of the brain, these " Negri bodies" are most regularly 

 present and numerous in the larger cells of the hippocampus major and 

 in the Purkinje cells of the cerebellum. The presence of these structures 

 in rabid animals and man has been confirmed by a large number of 

 workers in various parts of the world, and the specific association of these 

 bodies with the disease is now beyond doubt. In consequence, the 

 determination of " Negri bodies 7 ' in the brains of suspected animals has 

 become an extremely important method of diagnosis more rapid and 

 accurate than the methods previously known. 



The demonstration of Negri bodies in tissues is carried out as follows : 

 A small piece of tissue is taken from the cerebellum or from the center 

 of the hippocampus major (cornu ammonis), and is fixed for twelve 

 hours in Zenker's fluid. It is then washed thoroughly in water and 



1 Babes, Virch. Arch., 110, and Ann. de 1'inst. Pasteur, 6, 1892. 



2 Van Gehuchten, Bull, de 1'acad. de med. et biol., 1900. 



3 Negri, Zeit. f . Hyg., xliii and xliv. 



