Abstracts

Rationale: There is limited evidence on the management of patients with glutamic acid decarboxylase (GAD) antibody associated autoimmune epilepsy, or GAD positive (GAD+) epilepsy. We describe six GAD+ epilepsy patients presenting with seizure and refractory status epilepticus with special emphasis on the longitudinal electrographic changes in relationship to immunologic and anti-seizure medication therapies.

Methods: Six patients diagnosed with GAD+ epilepsy from 2016-2020 were retrospectively analyzed from patient records. We collected data about symptom onset, GAD65 antibody levels, MRI findings, continuous EEG results, immunotherapy, and anti-seizure medication (ASM) timing and treatment responses. The study was approved by the Georgetown University IRB.

Results: Of the six patients studied, four were male and two were female aged 42-80 years at symptom onset. Detailed demographics and clinical information are in Table 1. Anti-GAD antibody was checked in either CSF or serum using either immunofluorescence assay or cell-based assay at ARUP or Mayo Laboratory Diagnostics. Serum anti-GAD antibody titers ranged from 0.09 to greater than 2000 nmol/l (cut-off at 0.03 nmol/l). One patient had the simultaneous presence of other anti-neuronal antibodies (N-Type Calcium Channel Ab and P/Q-Type Calcium Channel Ab). One patient had co-existing stiff person syndrome and the rest encephalitis and epilepsy. All patients presented with new onset seizure with three patients having refractory status epilepticus (Table 1). Longitudinal continuous EEG changes before and after immunotherapy were collected. There were various EEG features in all six patients including: background slowing (n=6), electrographic seizure (n=4), interictal discharges (LPD, sharp waves) (n=4). Two patients were placed on anesthetics to achieve burst-suppression in EEG.

Four of the six GAD+ epilepsy patients underwent immunotherapy (IVMP, IVIG or PLEX) (Table 1, Column 6) while the remaining two could not tolerate immunotherapy due to multiple comorbidities. Of the four patients who had immunotherapy, three had clinical improvement while one died due to co-existing cancer.

Four of the six patients had status epilepticus (Table 1, Column 4) and three had super-refractory status epilepticus characterized by continued seizures despite trials of several ASMs and anesthetics. In the three patients with super-refractory status epilepticus, seizures re-emerged after undergoing burst-suppression. Two of these patients, subsequently, underwent immunotherapy with successful cessation of status epilepticus within two weeks. Interestingly, these two patients also had resolution of interictal and ictal EEG abnormalities before clinical improvement was observed.

Conclusions: GAD+ epilepsy was controlled more effectively with immunotherapy than ASMs. Serial continuous EEG monitoring can serve as a biomarker for disease outcome.

Funding: Please list any funding that was received in support of this abstract.: None.