Clinical characteristics of four patients with temporal lobe epilepsy associated with elevated anti-GAD antibodies

Anti-glutamic acid decarboxylase (GAD) antibodies are known to be associated with insulin-dependent diabetes mellitus (IDDM), stiff-person syndrome, and other neurological symptoms including temporal lobe epilepsy (TLE), known as autoimmune epilepsy. We treated four patients with TLE who had elevated titers of serum anti-GAD antibody (anti-GAD-Ab), higher than 100 U/ml. Three of the four patients started to have epileptic seizures in their 5th or 6th decade. Characteristic symptoms suggesting encephalitis or encephalopathy were absent at onset of these symptoms, which led to delayed diagnosis. All four patients developed two or three of cerebellar ataxia, neuropsychological impairment, and IDDM, by several years or decades after onset of TLE, even after seizure freedom in two patients. These abnormalities were indicators for suspecting the involvement of anti-GAD-Ab in the pathogenesis. Anti-GAD-Ab levels in the cerebrospinal fluid (CSF) were measured, which detected elevated CSF/serum anti-GAD-Ab ratio ( 1.0), suggesting intrathecal anti-GAD-Ab synthesis, in three of the four patients. The TLE symptoms were somewhat prolonged, but three of the four patients eventually achieved seizure freedom after immunotherapies with combinations of two or three anti-epileptic drugs. Serum anti-GAD Ab is recommended to be measured in patients with middle-Aged onset TLE. Moreover, immune-modulating therapies including steroid pulse and intravenous immunoglobulin therapies could have ameliorated neurological complications, even in the chronic phase.