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Immunological Mechanisms in the Aetiology of Epilepsy

Implications for Treatment

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Abstract

About 30 years ago, an autoimmune reaction was hypothesised in animal models of epilepsy and for the genesis of the ‘mirror focus’ in some patients with refractory epilepsy. However, this hypothesis did not attract attention among clinicians. During the 1950s, cortisone and corticotropin appeared to be efficacious in some epileptic syndromes, but the link with the immune system was not made. Furthermore, controlled studies were not rigorously planned and the best dosage and schedule still remain unknown. Later, immune deficits were described in patients with epilepsy, but the origin (disease-related or treatment-related) of these deficits is still open. An immunogenetic predisposition was also described in these patients, but results were often contradictory. During the 1980s, the successful use of intravenous immunoglobulin (IVIg) in childhood epilepsies again suggested a possible autoimmune process in some patients.

During the last few years, specific autoantibodies have been found in Rasmussen disease and other epileptic syndromes. Immunomodulatory treatments (IVIg, plasmapheresis) have been used with significant success in refractory epilepsies, and IVIg is considered by most epileptologists as the first-choice treatment in Rasmussen syndrome.

Recent work has shown that autoantibodies directed against some brain components might interact with ion-gated channels or neurotransmitters and therefore affect the stability of neuronal membranes. Autoimmune mechanisms are considered possible in the process of epileptogenesis. Taking this hypothesis further, immunomodulatory treatment at the time of brain injury (such as by trauma, prolonged seizures or stroke) could offer a preventive approach against epileptogenesis and therefore prevent recurrent seizures.

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  1. Centre Neurologique William Lennox, Universite Catholiqué de Louvain, Allée de Clerlande 6, Ottignies-LLN, B-1340, Belgium

    Kenou van Rijckevorsel

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van Rijckevorsel, K. Immunological Mechanisms in the Aetiology of Epilepsy. BioDrugs 12, 115–127 (1999). https://doi.org/10.2165/00063030-199912020-00003

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