{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:51:27Z","timestamp":1792263087618,"version":"4.4.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Pathogenic variants in\n                      <jats:italic>SLC6A1<\/jats:italic>\n                      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\n                      <jats:italic>SLC2A1<\/jats:italic>\n                      ,\n                      <jats:italic>CHD2<\/jats:italic>\n                      , and\n                      <jats:italic>CACNA1A<\/jats:italic>\n                      \u2010related disorders, where acetazolamide (ACZ) has shown beneficial effects. We assessed the efficacy of ACZ as an adjunctive treatment in patients with SLC6A1\u2010related neurodevelopmental disorder (SLC6A1\u2010NDD) and drug\u2010resistant seizures. We recruited patients with genetically confirmed pathogenic\n                      <jats:italic>SLC6A1<\/jats:italic>\n                      variants and drug\u2010resistant seizures treated with add\u2010on 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\u2009years were included. The mean dose of ACZ was 16.2\u2009mg\/kg\/day, and the mean treatment duration was 30\u2009months. 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\u2010resistant\n                      <jats:italic>SLC6A1<\/jats:italic>\n                      \u2010related seizures. Prospective studies with larger cohorts and standardized outcome measures are necessary to confirm the efficacy and long\u2010term safety of ACZ in this population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      Pathogenic\n                      <jats:italic>SLC6A1<\/jats:italic>\n                      variants in children cause developmental delay with behavioral issues, seizures, and often ataxia. In six children with drug\u2010resistant seizures, adjunctive acetazolamide (ACZ) led to seizure freedom in three and a 50\u201390% 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\u2010related neurodevelopmental disorder when standard treatments fail, warranting further study.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70155","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T06:50:51Z","timestamp":1761288651000},"page":"2009-2017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adjunctive acetazolamide for drug\u2010resistant seizures in\n                    <scp>SLC6A1<\/scp>\n                    \u2010related neurodevelopmental disorder: An\u00a0exploratory case series"],"prefix":"10.1002","volume":"10","author":[{"given":"Gia","family":"Melikishvili","sequence":"first","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9512-912X","authenticated-orcid":false,"given":"Olivier","family":"Dulac","sequence":"additional","affiliation":[{"name":"AdPueriVitam  Antony France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otar","family":"Koniashvili","sequence":"additional","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"},{"name":"Department of Pediatrics Stony Brook Children's Hospital  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgi","family":"Mamardashvili","sequence":"additional","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"},{"name":"Tbilisi State Medical University  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Gachechiladze","sequence":"additional","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazhi","family":"Tabatadze","sequence":"additional","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Melikishvili","sequence":"additional","affiliation":[{"name":"MediClubGeorgia Medical Center  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimma","family":"Gamirova","sequence":"additional","affiliation":[{"name":"Department of Neurology with Courses in Psychiatry, Clinical Psychology, and Medical Genetics Kazan Federal University  Kazan Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Tomenko","sequence":"additional","affiliation":[{"name":"Ural Federal University  Yekaterinburg Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Bakhtin","sequence":"additional","affiliation":[{"name":"Children's Regional Clinical Hospital Ministry of Health of the Krasnodar Region  Krasnodar Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Freed","sequence":"additional","affiliation":[{"name":"SLC6A1 Connect  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bossi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences University of Insubria  Varese Italy"},{"name":"Centre for Neuroscience University of Insubria  Varese Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruria","family":"Ben\u2010Zeev","sequence":"additional","affiliation":[{"name":"Sheba Medical Center, Pediatric Neurology Edmond and Lily Safra Children's Hospital  Ramat Gan Israel"},{"name":"Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kluger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Institute of Rehabilitation, Transition and Palliation of Neurologically Ill Children, Member of ERN EpiCARE Paracelsus Medical University  Salzburg Austria"},{"name":"Center for Pediatric Neurology, Neurorehabilitation and Epileptology Schoen Clinic Vogtareuth  Vogtareuth Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Falace","sequence":"additional","affiliation":[{"name":"IRCCS \u2018Giannina Gaslini\u2019, Full Member of ERN Epicare  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0668-5955","authenticated-orcid":false,"given":"Kai","family":"Kaila","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Biosciences (MIBS) and Neuroscience Center (HiLIFE) University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"IRCCS \u2018Giannina Gaslini\u2019, Full Member of ERN Epicare  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa 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Burr\u00e9J CrossJ ShaffoFC PrenticeB BrownsteinCA et\u00a0al.4\u2010Phenylbutyrate for STXBP1 and SLC6A1: safety tolerability seizure and EEG outcomes. 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