Enigmatic intractable Epilepsy patients have antibodies that bind glutamate receptor peptides, kill neurons, damage the brain, and cause Generalized Tonic Clonic Seizures.

Epilepsy affects 1-2% of the world population, is enigmatic in 30% of cases, and is often intractable, unresponsive to antiepileptic drugs, and accompanied by cognitive, psychiatric and behavioral problems. Tests for Autoimmune Epilepsy are not performed routinely, and limited to passive diagnosis of known autoimmune antibodies, without essential functional tests to reveal active pathogenic antibodies. We investigated two young Epilepsy patients with different Epilepsy characteristics, repeated intractable seizures, and enigmatic etiology. We suspected Autoimmune Epilepsy. We found that both patients have elevated IgG antibodies, and three types of glutamate receptor antibodies, to: AMPA-GluR3B, NMDA-NR1 and NMDA-NR2 peptides. In contrast, they lack autoantibodies to: LGI1, CASPR2, GABA-RB1, Amphiphysin, CV2, PNMA1, Ri, Yo, Hu, Recoverin, Soxi and Titin. IgG antibodies of both patients bound and killed human neural cells In vitro. Moreover, In vivo video EEG studies in naive rats revealed that patient's IgG antibodies, infused continually into rat brain, bound neural cells in the hippocampus and cortex, caused neural loss in these brain regions, and induced recurrent Generalized Tonic Clonic Seizures. We assume they can do so also in the patient's brain. This is the first model of human Autoimmune Epilepsy in rats. It can serve for discovery of patient's pathogenic antibodies, and drug development. Tests for autoimmune antibodies that bind glutamate receptor peptides, and functional diagnostic tests, are obligatory in all enigmatic intractable Epilepsy patients. Current diagnosis of Autoimmune Epilepsy is insufficient! If pathogenic antibodies are found, intractable patients must receive available, suitable and potentially life-changing immunotherapies for Autoimmune Epilepsy.