Authors :
Gia Melikishvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Presenting Author: Tamar Gachechiladze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Giorgi Mamardashvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Gvantsa Labadze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Tekla Koberidze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Otar Koniashvili, MD – Stony Brook Children’s Hospital, Stony Brook, New York, USA
Mariam Melikishvili, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Nazhi Tabatadze, MD – MediClubGeorgia Medical Center, Tbilisi, Georgia.
Ganna Balgura, MD – IRCCS Giannina. Gaslini
Antonella Riva, MD – University of Genoa
Ulviyya Guliyeva, MD – MediClub Hospital
Pasquale Striano, MD, PhD – IRCCS Giannina. Gaslini
Rationale:
STXBP1-related neurodevelopmental disorder (NDD) is an early-onset epileptic encephalopathy characterized by drug-resistant seizures, developmental delay, movement disorders, and ataxia. Despite extensive therapeutic trials, treatment remains largely unsatisfactory [1,2]. Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has shown unexpected efficacy in other monogenic epilepsies [3-5], but to date its use in STXBP1-related NDD has not been reported. We present four cases highlighting both seizure and non-seizure benefits of ACZ in STXBP1 patients.
Methods:
Four unrelated patients with genetically confirmed STXBP1 variants and drug-resistant epilepsy received adjunctive ACZ following failure of multiple antiseizure medications (ASMs). Clinical outcomes included seizure frequency, EEG changes, motor/ataxia symptoms, developmental progress, and ACZ dosing.
Results:
Across four patients with STXBP1-related NDD, acetazolamide (17–25 mg/kg/day) produced rapid and marked clinical benefits. Three patients achieved complete seizure freedom within two weeks, and one showed dramatic EEG improvement with cessation of spasms and normalization of background activity (Figure 1A,B). Beyond seizure control, two patients experienced striking improvements in ataxia, tremor, motor abilities, and social interaction. Overall, ACZ was effective not only for drug-resistant seizures but also for motor dysfunction.
Conclusions:
ACZ demonstrated remarkable efficacy in this series of STXBP1 patients, achieving seizure control, in otherwise refractory cases (Figure 1 C,D) and, uniquely, improving ataxia and tremor. This is the first report of ACZ use in STXBP1-related disorder and the first targeting epileptic spasms and ataxia in this context. Our findings suggest ACZ may represent a valuable therapeutic option for both epileptic and motor manifestations in STXBP1-related NDD, warranting systematic evaluation in larger cohorts.
References
- Freibauer A, Genes 2023.
- Dong M, Front Pediatr 2022.
- Le Roux M, Eur J Paediatr Neurol 2021.
- Málaga I, Epilepsia 2023.
- Melikishvili G, Epilepsia Open 2024.
Figure 1. EEG tracings (sensitivity 10 µV/mm; speed 30 mm/s; LPF 0.5 Hz; HPF 70 Hz). A–B: 8-month-old boy with epileptic spasms; before (A) and after initiation of ACZ (B), longitudinal bipolar montage.
C–D: 6-year-old girl with tonic–clonic and myoclonic seizures; baseline EEG consistent with epileptic encephalopathy. Recordings before (C) and during acetazolamide treatment (D), monopolar montage
Funding: None.