Authors :
Presenting Author: Tomasz Mieszczanek, MD, PhD – Department of Child Neurology, Danish Epilepsy Center, Dianalund, Denmark
Orrin Devinsky, MD – NYU Comprehensive Epilepsy Center, NYU Langone Medical Center
Cathrine Gjerulfsen, MD – Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark
Marina Nikanorova, MD – Department of Child Neurology, Danish Epilepsy Center, Dianalund, Denmark
Kern Olofsson, MD – Department of Child Neurology, Danish Epilepsy Center, Dianalund, Denmark
Guido Rubboli, MD – Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Rikke Moller, PhD – Danish Epilepsy Center Filadelfia
Anna Jakobsen, PhD – Department of Psychology University of Southern Denmark, Danish Epilepsy Center, Filadelfia, Dianalund, Denmark
Rationale:
GABA is the major inhibitory neurotransmitter in the human brain exerting its effects primarily on the ionotropic GABAA receptor (GABAA-R). Pathogenic loss-of-function (LoF) variants in the GABAA-R subunit genes (eg. GABRA1, GABRB2, GABRB3 or GABRG2 and GABRD) can cause epilepsy syndromes and drug-resistant epilepsy. The phenotypic spectrum ranges from mild genetic generalized epilepsies to severe early onset developmental and epileptic encephalopathy (DEE).
Vinpocetine, an alkaloid derived from the periwinkle plant, has been reported to have vasodilatory, cognition enhancing and anti-seizure effects. The anti-seizure effect may be due to the inhibition of sodium channel and positive modulation of GABAA receptors.
Methods:
Patients with pathogenic LoF GABAA-R variants in add-on treatment with vinpocetine were included. Data was collected retrospectively by the treating physician in collaboration with patient caregivers.
The seizure frequency before and during treatment with vinpocetine was provided by caregivers in seizure calendar.
Electroencephalograms (EEG) and neuropsychological examination were performed at baseline and during the treatment process. The Wechsler Intelligence Scale adapted to age and adaptive behavior by Vineland Adaptive Behavior Scales (VABS-III) were used in neuropsychological evaluation.
Adverse effects related to vinpocetine and possible reasons for discontinuation were analyzed.
Results:
Seven patients with add-on vinpocetine therapy between 2018 and 2025 were studied. 6 were treated in Denmark and 1 in the United States. Patients were ages 6-29 years, 5 male and 2 female. Three patients had epileptic seizures before starting vinpocetine and 4 were seizure free at baseline. One patient with myoclonic seizures, focal impaired aware seizures and focal-to-bilateral tonic-clonic seizures was seizure free after vinpocetine was added. Seizure frequency was unchanged in the other two patients. All of patients were on antiseizure mono- or polytherapy medication at baseline. Vinpocetine dose was 1mg/kg/day with a maximal dose 70mg per day divided into three daily doses. Decreased interictal epileptiform discharges spike-index was reduced in 4 patient’s EEGs during vinpocetine compared to baseline.
All patients were intellectual disabled and three of them also had autism spectrum disorder, two attention-deficit-hyperactivity disorder and one anxiety and obsessive-compulsive disorder (OCD). Improvement in OCD, anxiety and depression leading to discontinuation of risperidone in one patient. Less autistic behavior, more empathy, increased attention level and adaptive behavior and increased vocabulary was observed in other patients. Neuropsychological tests are being collected and analyzed and will be presented on a poster.
Headache was the most common side effect of treatment with vinpocetine, noted in two patients and tinnitus in one patient.
Conclusions:
Vinpocetine add-on therapy may be considered in patient with pathogenic LoF GABAA-R variants, with evidence that this can reduce seizures, interictal epileptic discharges and behavioral disorders, as well as improving adaptive behavior and cognition.
Funding: No founding