Research & Innovation
Publications
Adjunctive acetazolamide for drug-resistant seizures in SLC6A1-related neurodevelopmental disorder
PMU Author
Gerhard Kluger
All Authors
Gia Melikishvili, Olivier Dulac, Otar Koniashvili, Giorgi Mamardashvili, Tamar Gachechiladze, Nazhi Tabatadze, Mariam Melikishvili, Rimma Gamirova, Tatyana Tomenko, Igor Bakhtin, Amber Freed, Elena Bossi, Bruria Ben-Zeev, Gerhard Kluger, Antonio Falace, Antonella Riva, Kai Kaila, Pasquale Striano
Journal association
Epilepsia Open
Abstract
Pathogenic variants in SLC6A1 cause a neurodevelopmental disorder characterized by developmental delay with behavioral disturbances, seizures, often pharmacoresistant, and a spectrum of movement disorders such as ataxia. A similar triad is observed in other monogenic conditions, such as SLC2A1, CHD2, and CACNA1A-related disorders, where acetazolamide (ACZ) has shown beneficial effects. We assessed the efficacy of ACZ as an adjunctive treatment in patients with SLC6A1-related neurodevelopmental disorder (SLC6A1-NDD) and drug-resistant seizures. We recruited patients with genetically confirmed pathogenic SLC6A1 variants and drug-resistant seizures treated with add-on ACZ. The medical records were reviewed to evaluate changes in seizure frequency and severity, and to document adverse events. Improvements in ataxia and social interaction were determined by clinical judgment together with caregiver reports. Six patients with a mean age of 7 years were included. The mean dose of ACZ was 16.2 mg/kg/day, and the mean treatment duration was 30 months. Three (50%) patients achieved full seizure remission, and the remaining three patients had a reduction in seizure frequency ranging from 50 to 90%. Except for weight loss in one patient, no serious adverse effects were reported. Three out of four patients with baseline ataxia showed improvement. Caregivers noted improvement in social interaction and school engagement in five out of six patients. ACZ may offer a promising therapeutic option for drug-resistant SLC6A1-related seizures. Prospective studies with larger cohorts and standardized outcome measures are necessary to confirm the efficacy and long-term safety of ACZ in this population.Plain Language Summary Pathogenic SLC6A1 variants in children cause developmental delay with behavioral issues, seizures, and often ataxia. In six children with drug-resistant seizures, adjunctive acetazolamide (ACZ) led to seizure freedom in three and a 50-90% reduction in the others. Improvement in ataxia and behavior, with better social and school performances, was reported. One child had mild weight loss. These early findings suggest ACZ may be a safe, effective, and affordable option for SLC6A1-related neurodevelopmental disorder when standard treatments fail, warranting further study.
Keywords
GABA, EPISODIC ATAXIA, AUTISM, PHOTOSENSITIVITY, Ataxia, Acetazolamide, Developmental delay