A chronic experimental allergic encephalomyelitis (EAE) has been produced in rabbits sensitized with bovine white matter proteolipid apoprotein. Eleven of 12 animals developed clinical disease one to six months after immunization with a single dose of the apoprotein. The clinical course was characterized by posterior ataxia, flaccid paralysis progressing to spastic paralysis, and incontinence. Spontaneous relapses and remissions were observed in 3 rabbits. Histologically, acute and chronic encephalomyelitis accompanied by primary demyelination were observed. Serum antibody production, assayed by both an enzyme-linked immunosorbent assay and an electroblot procedure, did not correlate with either the clinical course or the histopathological findings. Delayed hypersensitivity to proteolipid apoprotein was observed in all rabbits prior to the onset of clinical signs. The data suggest that lymphocytes specifically sensitized to the proteolipid may be involved in the pathogenesis of the demyelination in chronic EAE.

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Central nervous system (CNS) myelin-specific antiserum was capable of initiating primary demyelination within 24 h following injection into the dorsal column of guinea pig spinal cord. Control serum injected in the same manner did not produce demyelination. The demyelinating lesions occurred as focal linear plaques of completely denuded intact axons surrounded by partially demyelinated and myelinated normal axons. Antiserum-mediated demyelination was followed by mononuclear cell infiltration 7-10 days later. Ultrastructural examination revealed vesiculation of myelin followed by cleavage of myelin lamellae at the intraperiod line. Remyelination began between 7 and 10 days following injection and correlated well with clinical evidence of recovery. The results of this study point to the importance of circulating antimyelin antibodies in the pathogenesis of demyelinating encephalitis. The model represents an in vivo approach to the study of the pathogenesis of immune-mediated myelinolysis in demyelinating disorders like multiple sclerosis (MS), subacute sclerosing panencephalitis (SSPE), and canine distemper encephalitis (CDE).