title: The pathogenesis of virus-associated encephalopathies: a prospective study of immunological mechanisms.
abstract: Thirty-two patients, including 29 children, presenting with acute unexplained encephalopathies were studied prospectively for evidence of virus infection, immunodeficiency, and immunologic involvement in the pathogenesis of their illnesses. Twenty-five of these patients had a clinical diagnosis of encephalitis. Twenty-two of these 25 had laboratory evidence of active virus infection, the majority with viruses usually associated with self-limiting illness outside the central nervous system. In patients with encephalitis, immune competence, as reflected by T-cell numbers and subsets in peripheral blood, in vitro interferon production, natural killer activity, and specific antiviral antibody production, was normal. Transudation of albumin into the cerebrospinal fluid (CSF), a measure of blood-brain barrier breakdown, was seen in 40% of patients. Intrathecal antibody synthesis was suggested by an elevated IgG index in 9/20 CSF/serum pairs but was confirmed by an elevated specific IgG ratio in only 3. The serum IgG1 and IgG3 subclass levels were significantly elevated at the time of the illness and remained elevated 8 months later; IgG2 and IgG4 levels were normal. IgE levels were elevated in 50% of patients. Serum levels of IgM antibodies against Escherichia coli measured 8 months after the neurological illness were also significantly higher in encephalitis patients than in age-matched healthy controls. Human myelin basic protein did not induce proliferation in peripheral blood lymphocytes in any patient. We conclude that most encephalopathies associated with viral infections are not due to an underlying generalized immunodeficiency, and probably result from an inappropriately vigorous immune response.
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D001812:Blood-Brain Barrier; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology / Q000473:pathology