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Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies

Abstract

Chronic encephalitis has been recognized as a cause of epilepsy since the work of Rasmussen et al. in the late 1950s. Despite this, few immunohistochemical studies of the affected brain tissue have been attempted. We have studied specimens of brain tissue from seven patients with this condition who underwent therapeutic multilobar cortical resection or hemispherectomy. Immunohistochemical studies were carried out using antibodies to glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA, PC10), T lymphocytes (UCHL-1), B lymphocytes (L26), macrophages and microglia (HAM-56), and major histocompatibility complex molecules (LN3 and β2microglobulin). Additionally, the results of preliminary immunohistochemical and ultrastructural investigation of possible immune complex deposition in blood vessel walls of affected brain tissue are presented. The pattern of GFAP immunoreactivity suggested a patchy and/or laminar disease process in most patients. GFAP immunoreactive cells were especially prominent around microvessels in some cases, suggesting an abnormality of the blood-brain barrier. Both microglial nodules and perivascular collections of inflammatory cells, seen to a variable extent in all cases, contained abundant cells immunolabelled with UCHL-1, LN3 and β2microglobulin. L26-labelled B lymphocytes were extremely sparse. Anti-PCNA frequently labelled microvascular endothelial cells, rare pericytes and occasional cells with microglial/macrophage morphology. The data suggest that chronic encephalitis found in patients with epilepsy results from patchy but widespread parenchymal brain injury, in the course of which cells of both microglial and lymphocyte series accumulate or proliferate within brain. Despite the lack of clear evidence of a causal viral pathogen from other studies, the predominant T cell lymphocytic infiltrate is consistent with a viral cause for this disorder. However, autoimmune factors (possibly triggered by viral infection) may contribute to the extensive neuropathological abnormalities. Very preliminary results using anti-IgG immunocytochemistry showed that in Rasmussen's encephalitis brain there was scattered labelling of neuronal cell bodies and some microvessels. Ultrastructural examination of brain tissue from one patient also showed unusual electron-dense material in microvascular endothelial basement membranes.

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Farrell, M.A., Droogan, O., Secor, D.L. et al. Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies. Acta Neuropathol 89, 313–321 (1995). https://doi.org/10.1007/BF00309624

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  • DOI: https://doi.org/10.1007/BF00309624

Key words

  • Blood-brain barrier
  • Encephalitis
  • Immunocytochemistry
  • Macrophages
  • Microglia