THE HISTOLOGY OF DISSEMINATED SCLEROSIS. 659 



of evidence, however, goes to prove that an infiltrative myelitis is usually due to an 

 organismal cause, and most workers conclude that areas of necrosis, without cell 

 infiltration and independent of vascular thrombosis, must be ascribed to toxic 

 influences. The toxic myelitis of pregnancy may be given as an evidence of the 

 result of an auto-intoxication which is often responsible at the same time for serious 

 trouble in connection with the cardiac and renal functions. 



Turning now to the histological data previously given, it will be recalled that the 

 conviction has been expressed that nowhere was there evidence of a primary vascular 

 inflammation, but that the first evidence of cell increase in the adventitia was an 

 infiltration of fat granule cells consequent to resorptive processes, that the subsequent 

 proliferation of adventitial cell elements was secondary to and probably caused by 

 this infiltration, and that only at a still later stage was there an infiltration of small 

 lymphocyte-like cells analogous to those found in all chronic processes. It has been 

 further stated that the histological observations lead to the conclusion that the 

 stimulus acts primarily on the myelin, and almost simultaneously on the glia cells, 

 surrounding the blood-vessels. The changes which have been outlined in a normally 

 developing " early " area are thus much more nearly allied to those of a toxic 

 myelitis than those of an infective myelitis, and differ from the former only in degree. 



In the absence, however, of any definite proof of such a toxin either in the blood 

 or cerebro-spinal fluid, other evidence must be submitted with great reserve. The 

 example of general paralysis, in which disease Noguchi has demonstrated the pre- 

 sence of the spirochseta pallida in the cortex, but which formerly was ascribed to a 

 chronic toxic encephalitis of lymphatic origin, must serve to show how quickly views 

 regarding the pathogenesis and etiology of a disease may require to be modified. In 

 this instance, however, it may be stated that the most recent writers on this subject, 

 M'Intosh and Fildes, look upon the inflammatory reactions — peri-vascular infiltra- 

 tion of lymphocytes and plasma cells involving the vessels of the pia and those that 

 penetrate the cerebral substance; "primary degeneration" of the neurons; and 

 proliferation of the glia — as all due to a primary reaction to the spirochaeta pallida 

 and not primary or secondary to one another : while Nonne (quoted by those writers) 

 looks upon the lesions not as the direct result of the activity of the spirochaeta 

 pallida but as due to the action of the toxins, derived from them, which have a 

 special affinity for nerve areas. 



The important point, however, in relation to disseminated sclerosis is that 

 experimental work has proved that circumscribed areas may be attacked by toxic 

 materials, and that in such areas the first effect is on the nerve fibres and inter- 

 stitial tissue surrounding the blood-vessels and only secondarily on the vessel walls 

 themselves. The causal agent must be a weak one compared to the usual agents 

 which produce toxic myelitis, for there is evidence of a slow, often limited and 

 localised action, and the subacute onset in the relapses again argues for its slight 

 intensity. For such a chronic course as disseminated sclerosis usually runs, with 



