g(m1)-ganglioside and Epilepsy

To determine the prevalence of serum antibodies to the ionotropic glutamate receptor 3 (GluR3) in patients with Rasmussen encephalitis (RE), a severe epileptic disorder, and to compare with serum from control subjects and patients with intractable epilepsy (IE).. The authors looked for serum immunoglobulin (Ig) G antibodies to GluR3 in 30 patients with RE, including two patients who had plasma exchange and 12 who had been treated with IV Igs with varying results, and 49 patients with IE and 23 healthy individuals, using ELISA with GluR3B peptide, Western blot analysis of recombinant full-length GluR3, immunoprecipitation of [35S]- and [125I]-labeled GluR3 extracellular domains, immunohistochemistry on rat brain sections, and electrophysiology of GluR3 expressed in Xenopus oocytes.. Low levels of antibodies to the GluR3B peptide were detected using ELISA in only 4 of the 79 patients with epilepsy (2 with RE and 2 with IE); binding to GluR3B in other sera was shown to be nonspecific. One other patient with IE had antibodies to recombinant GluR3 on Western blot analysis. However, none of the sera tested precipitated either the [35S]- or the [125I]-labeled GluR3 domains; none bound to rat brain sections in a manner similar to rabbit antibodies to GluR3; and none of the nine sera tested affected the electrophysiologic function of GluR3.. GluR3 antibodies were only infrequently found in Rasmussen encephalitis or intractable epilepsy.

Topics: Adolescent; Adult; Aged; alpha7 Nicotinic Acetylcholine Receptor; Amino Acid Sequence; Animals; Antibodies, Anticardiolipin; Antibody Specificity; Autoantibodies; Autoantigens; Brain; Cell Line; Child; Child, Preschool; Encephalitis; Epilepsy; Epitopes; Female; G(M1) Ganglioside; Glutamate Decarboxylase; Humans; Infant; Middle Aged; Models, Molecular; Molecular Sequence Data; Protein Conformation; Rabbits; Rats; Receptors, AMPA; Receptors, Nicotinic; Recombinant Proteins; Sodium Channels

The role of antiganglioside antibodies (AGAs) in late post-apoplectic epilepsy (LPAE) was studied. Serum AGAs from 8 patients with large lobar infarctions were serially checked for 2.5 months. Sera from another 30 patients with fronto-temporoparietal (FTP) or frontal (F) infarction were obtained 3 months to 3 years after a stroke for AGA analysis. These 30 patients were followed up for 3 years following their strokes to determine if LPAE developed. Results showed that 7/8 patients with large lobar infarction showed increase in either anti-GT1b or anti-GM1 (IgM or IgG) within a few weeks, but levels returned to the baseline 2-3 months after stroke. LPAE occurred in 9/21 patients with FTP infarction and 5/9 with F infarction. There was no difference in AGAs among patients with FTP and F infarctions. Pooled data from these 2 groups showed no correlation between AGAs and LPAE. These data document for the first time that anti-GT1b and anti-GM1 antibodies can transiently increase after stroke, but their late titers are not associated with LPAE.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Cerebrovascular Disorders; Epilepsy; G(M1) Ganglioside; Gangliosides; Humans; Middle Aged

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.

Topics: Adult; Age of Onset; Aged; Animals; Antibody Specificity; Anticonvulsants; Autoantibodies; Drug Resistance; Epilepsies, Partial; Epilepsy; Female; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Middle Aged; Rats

Antibodies to GM1 ganglioside injected into the sensorimotor cortex of the rat induce recurrent epileptiform activity. We now find that the divalent F(ab')2 and monovalent Fab' fragments derived from antiganglioside IgG molecules are able to induce epileptiform seizures. This result supports the view that the binding of antibodies to ganglioside receptors in the synaptic membrane is sufficient in itself to initiate changes in membrane processes which lead to epileptiform spiking. These changes do not appear to be dependent on linking of ganglioside receptors or on the presence of serum factors such as complement.

Topics: Animals; Cerebral Cortex; Electroencephalography; Epilepsy; G(M1) Ganglioside; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunoglobulin M; Male; Rats; Rats, Inbred Strains; Receptors, Neurotransmitter; Synaptic Membranes

Topics: Amyotrophic Lateral Sclerosis; Animals; Brain; Brain Chemistry; Epilepsy; Female; G(M1) Ganglioside; Gangliosides; Humans; Memory; Mice; Pregnancy; Prenatal Exposure Delayed Effects; Tissue Distribution

Following observations that the intracerebral injection into rats of antiserum to brain gangliosides resulted in recurrent epileptiform activity and that seizure activity was not seen if antibodies were removed by absorption of the antiserum with pure GM1 ganglioside, a study was undertaken to establish characteristics of the immunological agents used to produce this model of epilepsy. It was determined that the potencies (antibody titers with GM1 ganglioside) of antiganglioside sera can be correlated with the intensities of epileptiform activity they induce; that immunoglobulin fractions from antiganglioside sera are even more effective biologically than the antisera; and that antibodies to GM1 ganglioside purified by affinity chromatography can also induce recurrent epileptiform discharges but are not as effective as either native antiserum or immunoglobulin fractions.

Topics: Animals; Disease Models, Animal; Electroencephalography; Epilepsy; G(M1) Ganglioside; Gangliosides; Immune Sera; Immunoglobulins; Rats; Seizures