Cryptogenic partial epilepsies with anti-GM1 antibodies: a new form of immune-mediated epilepsy?

We wished to study immune system dysfunction which has been proposed as a potential cause of epilepsy. Epileptogenic action of antibodies directed against GM1 gangliosides was demonstrated in rats, but the potential role of anti-GM1 antibodies in human epilepsy has not yet been studied.

We investigated the presence of IgG or IgM anti-GM1 antibodies in the sera of 64 patients with various types of epileptic syndromes: idiopathic generalized epilepsy (IGE) (n = 6), symptomatic or cryptogenic generalized epilepsy (SCGE) (n = 7), symptomatic partial epilepsy (SPE) (n = 26), and cryptogenic partial epilepsy (CPE) (n = 25).

Two patients had elevated titers of IgM anti-GM1 antibodies, one patient had elevated titers of both IgM and IgG anti-GM1 antibodies, and 1 patient had elevated titers of IgG anti-GM1 antibodies. All 4 patients had complex partial seizures (CPS) secondarily generalized, drug resistance, psychiatric disorders, and normal brain imaging. Anti-GM1 antibodies were never associated with IGE, SCGE, or SPE. We compared the reactivity of sera from these patients with the sera from 5 patients with motor neuropathies with conduction block (MNCB) against different gangliosides and concluded that epilepsy sera did not react with the Gal(beta 1-3)GalNAc epitope. Two anti-GM1-positive patients were treated successfully with high-dose intravenous immunoglobulins (IgIV).

Our findings suggest that detection of anti-GM1 antibodies could allow identification of a subgroup of patients with partial epilepsy associated with an autoimmune response. If anti-GM1 antibodies prove pathogenic, they could be an important prognostic factor for drug resistance and worsening of seizures.