F06. Anti-glutamic acid decarboxylase 65 antibody associated epilepsy

Abstract

Glutamic acid decarboxylase antibody-associated encephalitis has been increasingly recognized as an underlying etiology for both acute and chronic epilepsy with predominantly temporal lobe onset. However, this condition is challenging in both diagnosis and management. Imaging and CSF evidence of inflammation, and typical presentations should raise the suspicion of testing for the diagnostic antibodies. High antibody titer (⩾1000 U/ml by RIA or ⩾ 20 nmol/L) & evidence of intrathecal synthesis support the diagnosis. Unlike other immune-mediated epilepsies, GAD 65 antibody-mediated epilepsy often demonstrates poor response to both AEDs and initial immune therapy; long term treatment with more aggressive immunosuppressants such as Rituximab/Cyclophosphamide are often necessary. The electronic databases searched in the present study included the full-text database for articles published in PubMed, OVID and Midline from January 1974 to May, 2017. A total of 38 studies were found which included a total of 135 patients. We selected patients presented with a seizure as a main manifestations whom ended to have GAD-Abs positive. Both acute/sub acute and chronic/indolent presentations been observed. We studied the clinical Picture (Age, Sex, Type, clinical presentation), serum and CSF GAD-Abs, neurophysiological, neuroimaging findings, type of treatments and the outcome between 6 months up to 10 years. A total of 135 patients, 97 female and 35 male with median age of 32. 99 cases have temporal lobe epilepsy, 16 undetermined, 4, Multifocal, 4, hemispheric, 2, idiopathic generalized epilepsy, 6, frontal lobe epilepsy, and 2, JME. 36 manifested as limbic encephalitis with 4 cases ended with death and 99 (73.33%) as a chronic presentation. Seizure freedom observed in 24 patients, seizure improvement in 46 patients, and no improvements in 46 patients. In terms of CSF findings; 63 patients had strong serum GAD-Ab, 38 weak and 25 labeled as positive. Absent WBC in CSF were seen in the majority of cases 88.34% and elevated protein only in 14.56%. OCB were positive in 33 out of 52 tested patients. Intrathecal synthesis of GAD-Ab were positive in 30 out of 47 tested patients. Regarding neuroimmaging finding; normal MRI finding in 44 out of 106 tested patients and 62 with abnormal findings. 80.64% of cases have temporal lobe signals and 19.35% extratemporal. Autoimmune-mediated epilepsy is not as rare a disease as previously thought. GAD65-related epilepsy is more refractory and difficult to control when compared to other Ab-mediated epilepsies. Early diagnosis guides treatment and has the potential to reduce chronic seizure burden and prevent cognitive and psychiatric complications. Early initiation of immunotherapies should be undertaken before pathological effects spread to extra-temporal areas, which can make the patient more refractory to treatment. Further studies evaluating the underlying pathophysiology may influence future therapeutic management strategies.