Objective:

The objective of this study was to describe the evaluation for patients with drug-resistant epilepsy associated with high-titer GAD65 antibodies and compare clinical factors with a control group of patients with temporal lobe epilepsy and negative GAD65 antibodies.

Background:

High-titer GAD65 antibodies are associated with chronic temporal lobe epilepsy. The recognition of epilepsy associated with GAD65 antibodies has treatment and prognostic implications.

Design/Methods:

From a list of 1432 patients presented at a single institution Surgical Epilepsy Conference from 1/1/2007-6/13/2024, patients with epilepsy associated with high-titer serum GAD65 antibodies (>20 nmol/L) were identified. Charts were reviewed to describe clinical, EEG, and imaging characteristics. Age and sex matched controls with drug-resistant, temporal lobe epilepsy who were negative for high-titer GAD65 antibodies served as a control group.

Results:

Fifteen patients (13 females, 86.7%) were identified with drug-resistant epilepsy associated with high-titer GAD65 antibodies (median serum titer=960 nmol/L; range 34-4678 nmol/L). The median age of epilepsy onset was 25 years (range 4-44 years). All patients had temporal lobe epilepsy, with independent bitemporal onset seizures on scalp EEG in 7 patients (47%). Three patients initially presented with limbic encephalitis, and three patients developed mesial temporal sclerosis (2 bilateral, 1 unilateral). Limbic encephalitis, musicogenic seizures, and type 1 diabetes were only present in those with GAD65 antibodies when compared to the control group, but these differences did not reach statistical significance, nor did age of onset, seizure characteristics and frequency, autoimmune history, or EEG or imaging findings.

Conclusions:

High-titer GAD65 antibodies are associated with drug-resistant epilepsy, frequently with bitemporal involvement. While it may be difficult to differentiate those with GAD65-associated epilepsy from those with temporal lobe epilepsy not related to GAD65 antibodies, limbic encephalitis, musicogenic seizures, and type 1 diabetes were only observed in patients with GAD65-associated epilepsy.