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Early Treatment with Vigabatrin Does Not Decrease Focal Seizures or Improve Cognition in Tuberous Sclerosis Complex:
Elizabeth Martina Bebin1, Jurriaan M Peters2, Brenda E Porter3
1Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
Insights
Early vigabatrin treatment in tuberous sclerosis complex (TSC) infants did not improve neurocognitive outcomes. However, it was associated with a later onset and lower incidence of infantile spasms, indicating a potential benefit for specific seizure types.
Area of Science:
- Pediatric Neurology
- Epileptology
- Developmental Neuroscience
Background:
- Tuberous sclerosis complex (TSC) is a genetic disorder associated with epilepsy and developmental challenges.
- Early intervention is crucial for optimizing neurodevelopmental outcomes in infants with TSC.
- Vigabatrin is an established treatment for infantile spasms but its role in preventing other seizure types and improving overall neurocognition in TSC is under investigation.
Purpose of the Study:
- To evaluate the efficacy of early vigabatrin treatment, initiated upon epileptiform electroencephalogram (EEG) activity, versus treatment at seizure onset in infants with TSC.
- To determine the impact of early vigabatrin on neurocognitive outcomes at 24 months of age.
- To assess the effect of early vigabatrin on epilepsy incidence, drug-resistant epilepsy, and safety.
Main Methods:
- A phase IIb, multicenter, randomized, double-blind, placebo-controlled trial.
- Infants with TSC received either vigabatrin at the first epileptiform EEG or at seizure onset.
- Primary outcome: Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive score at 24 months.
Main Results:
- No significant differences in Bayley-III cognitive scores were observed between the early vigabatrin and placebo groups at 24 months.
- Early vigabatrin did not significantly alter the overall incidence or drug-resistant epilepsy rates compared to placebo.
- The vigabatrin group showed a lower incidence and later onset of infantile spasms, with similar adverse event profiles across groups.
Conclusions:
- Initiating vigabatrin based on EEG epileptiform activity before seizure onset does not improve 24-month neurocognitive outcomes in TSC infants.
- Preventative vigabatrin does not delay the onset or reduce the incidence of focal seizures and drug-resistant epilepsy in this population.
- Early vigabatrin treatment demonstrates a benefit in reducing the incidence and delaying the onset of infantile spasms in TSC infants.
Objective:
This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.
Methods:
A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.
Results:
Of 84 infants enrolled, 12 were screen failures, 4 went straight to open label vigabatrin, and 12 were not randomized (normal EEG throughout). Fifty-six were randomized to early vigabatrin (n = 29) or placebo (n = 27). Nineteen of 27 in the placebo arm transitioned to open label vigabatrin, with a median delay of 44 days after randomization. Bayley-III cognitive composite scores at 24 months were similar for participants randomized to vigabatrin or placebo. Additionally, no significant differences were found between groups in overall epilepsy incidence and drug-resistant epilepsy at 24 months, time to first seizure after randomization, and secondary developmental outcomes. Incidence of infantile spasms was lower and time to spasms after randomization was later in the vigabatrin group. Adverse events were similar across groups.
Interpretation:
Preventative treatment with vigabatrin based on EEG epileptiform activity prior to seizure onset does not improve neurocognitive outcome at 24 months in TSC children, nor does it delay onset or lower the incidence of focal seizures and drug-resistant epilepsy at 24 months. Preventative vigabatrin was associated with later time to onset and lower incidence of infantile spasms. ANN NEUROL 2023.
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