Autoantibodies and epilepsy.

Epilepsia. 2011 May;52 Suppl 3:18-22

Authors: Bien CG, Scheffer IE

Abstract
In a substantial number of patients with epilepsy, the etiology of the seizure disorder remains unknown. In recent years, the detection of autoantibodies has contributed to the etiologic understanding of a substantial number of so far unexplained epilepsies.

The associated syndromes are mainly related to the temporal lobes (with presentation as limbic encephalitis or chronic mediotemporal lobe epilepsy) or to extended brain areas (presenting as diffuse encephalopathies with seizures). However, the full spectrum of autoantibody-associated epilepsies is about to be determined. A promising example for this incipient expansion of the clinical spectrum is the description of a novel seizure type found in patients with antibodies to the voltage-gated potassium channel (VGKC) complex.

At present, the antibodies most relevant in epileptology are those directed to molecules on the surface of neurons, namely to components of the VGKC complex and to the N-methyl-d-aspartate-receptor; other antigenic targets located on the surface of neurons are the γ-aminobutyric acid (GABA)(B) -receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor.

There are several reasons to believe that these antibodies are directly pathogenic to the brain. Other autoantibodies target intracellular antigens like those directed to the enzyme glutamic acid decarboxylase (GAD) and the onconeural antibodies. Most researchers think that these antibodies are markers of the immunopathological process rather than being pathogenically active by themselves.

Especially the epilepsies associated with antibodies to surface antigens seem to respond to immunotherapies. This offers novel promising therapeutic avenues for the epileptologist. The precise pathogenic effects of autoantibodies still need to be elucidated.