Neurological disorders associated with glutamic acid decarboxylase (GAD) antibodies: clinical characteristics and short-term outcomes in a Russian cohort patients

Background. Glutamate decarboxylase (GAD) antibody-spectrum diseases (GAD-ASD) are a group of relatively rare immune-mediated neurological disorders that most commonly present by such syndromes as cerebellar ataxia (СA), stiff person syndrome (SPS), limbic encephalitis (LE), epilepsy (E) and variants of their combination (overlap syndromes). The domestic literature contains descriptions of individual cases of GAD-ASD; cohort studies of GAD-ASD have not been conducted in Russia previously. Aims — to analyze clinical features and short-term outcomes in different phenotypes of GAD-ASD in a one-center cohort of Russian patients. Methods. The study was conducted between 2018 and 2024 at Research Center of Neurology (Moscow, Russia). The object of the study were 40 patients with a verified diagnosis of GAD-ASD. An assessment of the clinical picture, the results of blood and cerebrospinal fluid (CSF) laboratory tests, MRI and neurophysiological studies were carried out, the data of treatment and patient’s follow-up were analyzed. Results. Most patients were female (85%). The median age at symptom onset was 54 years (range: 18–74 years), the duration of the disease was 40.5 months (range: 1 month — 14 years). The diseases phenotypes were typical for GAD-ASD: SPS (42.5%), MA (30%), LE/E (15%), overlap syndrome (12.5%). GAD antibodies were detected in 100% of the blood and CSF samples examined. 1 case (SPS) corresponded to a “probable” paraneoplastic syndrome; 3 cases (LE, SPS, MA+E) were associated with COVID-19. 62.5% of patients had another concomitant autoimmune disease. Inflammatory changes in the CSF were rare: increased protein — 3.4%, oligoclonal bands — 10%. On brain MRI, focal changes were observed in 5%, signs of atrophy — in 20%. Immunotherapy was performed in 80% patients, in 80% of them — long-term immunosuppression. Treatment response was observed in 92.1% and didn’t differ among GAD-ASD phenotypes. 65.8% of patients achieved improvement with a decrease in disability, 1 patient (2.6%) achieved complete recovery. Conclusions. In Russia, a cohort of patients with GAD-ASD has been characterized for the first time. In Russian patients, disease phenotypes were typical for GAD-autoimmunity, the most common of which was SPS. Most patients respond to immunotherapy, but recoveries are rare, indicating a chronic course of GAD-ASD.