Abstracts

Rationale: Titers of antibodies against glutamate decarboxylase (anti-GAD) are elevated more often in patients with epilepsy than in the general population. However, the clinical entity of anti-GAD associated epilepsy remains poorly defined. We present a large cohort of epilepsy patients with a positive anti-GAD antibody test and aim to define the core clinical symptoms and functional outcome.Methods: We report a retrospective observational cohort study of all patients in whom an anti-GAD analysis was requested between 2010 and 2014 at the Maastricht University Medical Center and Kempenhaeghe epilepsy center. Subjects for whom anti-GAD analysis was performed solely in the context of diabetes mellitus type 1 (DM1) were excluded. We screened patient records and included 119 patients presenting with neurologic or psychiatric disorders. To assess clinical characteristics, two independent (child) neurologists scored the core clinical symptoms (epileptic seizures, cognitive and/or psychiatric disorders, encephalopathy, movement disorder, ataxia and paresis), defined the clinical suspicion for autoimmune encephalitis and evaluated the seizure type without knowledge of anti-GAD status. Frequencies of patient characteristics and clinical symptoms were compared by a Chi-square test. We scored functional outcome using the modified Ranking Scale (mRS) at the time of diagnosis and after a period of 1 month, 6 months and 1 year.Results: Of a total of 119 patients, 17 were anti-GAD positive. Anti-GAD positive patients’ median age was 30 years (range 3–64; 11 female). There were 9 subjects suspected for autoimmune encephalitis and 8 only had refractory epilepsy. All anti-GAD positive patients had seizures with a dysfunction of cognition in 47% of cases. Psychiatric symptoms were significantly less common in anti-GAD positive patients (6% versus 33% in anti-GAD negative patients, p=0,021). There was no difference in seizure type. Autoimmune comorbidities were present in 12 (70%) anti-GAD positive patients, of which DM1 (n=8) was most common. At time of diagnosis 12 (70%) anti-GAD positive patients were functionally independent (mRS score 0 to 2). After 1 year, one of them died and one was symptom-free. From the 5 functionally dependent patients, 2 recovered to independence at 1 year.Conclusions: The clinical entity of anti-GAD related epilepsy may be defined as (refractory) epilepsy or encephalitis with a comorbid dysfunction of cognition, but psychiatric symptoms are rare. DM1 is a common autoimmune comorbidity in anti-GAD positive epilepsy patients. Anti-GAD related epilepsy might have a somewhat more favorable functional course over time than previously thought.