Epilepsy: an autoimmune disease?

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Abstract
Epilepsy may present as a symptom of many neurological disorders and often an aetiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation. The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy. ### RASMUSSEN'S ENCEPHALITIS Rasmussen's encephalitis is a rare progressive disorder of unilateral brain dysfunction, focal seizures, and inflammatory histopathology. It usually presents in middle childhood with intractable seizures and progressive neurological deficits culminating in hemiparesis. The seizures are often resistant to antiepileptic drugs. Treatment with corticosteroids, intravenous immunoglobulins (IVIg), or plasmapheresis has been reported to be beneficial in some.1 2 However, no blinded placebo controlled trials have been undertaken to confirm the efficacy of such treatments. In many children with Rasmussen's encephalitis control of their epilepsy may only be obtained by hemispherectomy. The serendipitous finding that rabbits immunised with a fusion protein of glutamate receptor (GluR) 3 (but not GluR 1, 2, 5, or 6) developed seizures and histopathological changes that mimicked Rasmussen's encephalitis initiated the Rasmussen's encephalitis autoimmune hypothesis.3 However, mice immunised with GluR3, which developed high concentrations of anti-GluR3 antibodies and brain pathology reminiscent of the disease did not go on to develop epilepsy.4 Antibodies against GluR3 (and GluR2 at low concentrations) have been detected in the serum of some patients with Rasmussen's encephalitis3; however, confirmatory reports from other groups and studies determining the frequency of these antibodies in consecutive series of patients with the disease are notable …