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 beta 2-microglobulin). 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 and perivascular collections of inflammatory cells, seen to a variable extent in all cases, contained abundant cells immunolabelled with UCHL-1, LN3 and beta 2-microglobulin. 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and staging of Rasmussen’s encephalitis by serial MRI and histopathology

“…The data provided in this study suggest a disease course in RE with the highest inflammatory intensity, as judged by the density of T cells 19,26 and microglial nodules, in the early stages, followed by a subsequent decrease in inflammation. Different cortical regions pass through these stages at different times, reflecting the manner in which the disease spreads ("march across the hemisphere" 7 ).…”

“…The main changes are observed in the cortex. 18,19 Histopathology still is regarded as the gold standard for establishing the diagnosis of RE. As an intra vitam tool for morphologic evaluation, MRI is becoming increasingly important in the diagnosis of RE, especially because not all investigators consider brain biopsy necessary for establishing the diagnosis.…”

AUTOIMMUNITY AND NEUROLOGICAL DISEASE: Antibody Modulation of Synaptic Transmission

“…This led to our discovery of similar evidence of human IgG and complement membrane attack complex (MAC) on neurons in the cortex of two of three RE patients but not three control patients with complex partial epilepsy (He et al 1997). Labeled neurons occurred in discrete patches separated by large areas of normal tissue; other histopathological changes such as neuron loss and inflammatory cell infiltrates likewise occurred in a multifocal pattern in RE patients (Farrell et al 1995). Because the lytic effects of complement deposition can prove fatal for targeted cells, neuronal complement deposition may contribute to the neuronal cell loss and cortical degeneration seen in RE.…”

Improvement in adult-onset Rasmussen’s encephalitis with long-term immunomodulatory therapy

“…Although we have few immunologic data, it may be relevant that in Patient 2 CSF IgG bands disappeared some time between 4 and 12 months after starting hIVIg. Because few B cells are detected by immunohistochemistry in brains of RE patients, 16 it is thought that circulating IgG enters the CNS via defects in the blood-brain barrier (BBB). 11,12 Thus, the delayed disappearance of CSF IgG might be a function of the time taken for the BBB to heal or of the half-life of CSF IgG.…”