DEMYELINATION IN SEVERE COMBINED IMMUNODEFICIENT, MICE BY INTRACISTERNAL INJECTION OF CEREBROSPINAL-FLUID CELLS FROM PATIENTS WITH MULTIPLE-SCLEROSIS - NEUROPATHOLOGICAL INVESTIGATION

Demyelinating lesions have been observed in severe combined immunodefi cient (SCID) mice after intracisternal administration of cerebrospinal fluid cells (CSFC) from patients with multiple sclerosis (MS). Furthe r investigation in our laboratory revealed that CSFC from 6 of 15 pati ents at exacerbation of MS caused demyelination. The factor leading to demyelination appears to be the high frequency of relapses during a s hort period, but not the severity of the disease. Neuropathological an d immunohistochemical studies revealed that a lack of inflammatory mon onuclear cell infiltration within and around the demyelinating lesions or in leptomeninges was a common characteristic in all SCID mice with CSFC-induced demyelination. In affected mice killed 2-3 weeks after i ntracisternal administration of CSFC, foamy/vacuolar lesions with a sm all or moderate number of lipid-laden macrophages were seen in the whi te mater. Ultrastructurally, relative preservation of axons, in contra st to myelinoclastic features, as well as some remyelinated axons were observed. In affected SCID mice killed 4-6 weeks after intracisternal administration, more widespread foamy macrophages and necrotic foci w ith poor remyelination were seen. The findings were similar to those s een in experimental allergic encephalomyelitis, though without lymphoc ytic infiltration, but were quite different from the lesions observed in Theiler's murine encephalitis virus infection. The absence of an im munohistochemical reaction to the human leukocyte common antigen in th e infiltrating mononuclear cells suggested that the graft-versus-host reaction was an unlikely cause of the demyelinating lesions.