Vigabatrin Demonstrates Significant Seizure Suppression in Super Refractory Status Epilepticus

R. Eugene Ramsay, MD

New study data presented at the 2023 American Epilepsy Society (AES) annual meeting, held December 1-5, in Orlando, Florida, suggests that vigabatrin may be a beneficial medication for patients with super-refractory status epilepticus (SRSE). All told, nearly all treated patients in the single-center study demonstrated seizure control and two-thirds had complete resolution of SE.¹

Led by R. Eugene Ramsay, MD, a faculty member at the Ochsner Medical Center in New Orleans, Louisiana, the retrospective cohort study comprised of 66 adults with RSE who were admitted to a single tertiary center. Within the cohort, SE was nonconvulsive in 53% of patients, convulsive in 30%, and both in 16.7%. Anoxic SE etiologies comprised 22.7% of the cohort and 66.7% of patients had no prior seizure history.

SRSE resolution was defined as the successful stopping of anesthetic agents without the return of epileptic activity on electroencephalogram. Following treatment, 29 of the 30 patients (96%) who had ongoing SE achieved seizure control through vigabatrin. Of this group, complete resolution of SE was achieved in 25 (69.4%) patients on the therapy. The cohort initiated treatment on average 7 days after the onset of SE and remained for a mean of 19 days, with a mean maximum daily dose of 3484.9 (±976.5) mg.

Coming into the study, more than half of the cohort (n = 33; 54.5%) had controlled SE. Following treatment with vigabatrin, SE resolution was recorded in 69.4% (n = 25) of this subgroup. In comparison, those with controlled SE prior to vigabatrin had higher odds of initiating treatment later (mean days after SE onset: 11.6 [±9.3] vs 3.8 [±3.8]; P <.001). Although having a non-anoxic etiology was associated with a higher likelihood of a more favorable treatment response (OR, 47.7; 95% CI, 3.7-1573.3; P = .009), all 15 anoxic patients achieved SE control (9 had SE control pre-treatment) and 5 (33%) tolerated complete wean of anesthetics.

In the study, 42 patients (63.6%) survived index hospitalization and 39 (88.6%) of these had resolution of SE. Investigators observed seizure control in patients with post-anoxic SE; however, 4 of 5 (80%) patients with post-anoxic SE died during hospitalization, most from withdrawal of care.

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Vigabatrin, an FDA-approved antiseizure medication since 2009, is designed to irreversibly inhibit y-amino butyric acid-transaminase (GABA-T), increase GABA, and indirectly lower glutamate levels. In 2020, its indication was expanded to the treatment of focal epilepsy at different ages. It currently is indicated for refractory focal epilepsy in children 2 years of age or older and adults, as well as infantile spasms in children 1 month to 2 years old.

In 2022, investigators initiated VIGAB-STAT, a phase 2a clinical trial assessing vigabatrin in post-anoxic status epilepticus (PACE). The hypothesis behind the study is that early inhibition of GABA breakdown may be possible in the post-cardiac arrest period, and may be an effective adjunctive treatment in PASE.²

VIGAB-STAT, an open-label, pilot study with blinded assessment, includes 12 patients with PACE who will receive a single loading dose of 4500 of vigabatrin via enteric tube within 48 hours after PASE onset. Vigabatrin levels will be monitored at baseline, 0.5, 1, 2, 3, 6, 12, 24, 48, 72, and 168 hours following initiation. The primary feasibility end point is the proportion of enrolled patients among identified eligible patients receiving vigabatrin within 48 hours of PASE onset while the primary pharmacokinetic end point is the measured vigabatrin level at 3 hours post-administration.

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REFERENCES
1. Ramsay RE, Busi K, Gao H, et al. Use of vigabatrin in the treatment of super refractory status epilepticus. Presented at: AES 2023; December 1-5; Orlando, FL. POSTER 3.273
2. Maciel CB, Teixeira FJP, Dickinson KJ, et al. Early vigabatrin augmenting GABA-ergic pathways in post-anoxic status epilepticus (VIGAB-STAT) phase 2a clinical trial study protocol. Neurol Research & Practice. 2022;4:4. doi:10.1186/s42466-022-00168-x