Authors :
Presenting Author: R. Ramsay, MD – International Center for Epilepsy
Katherina Busi, MD – Assoc Prof, Neurology, University of Florida; Hanzhi Gao, PhD – Assistant Professor, Neurology, University of Florida; Carolina Maciel, MD – Assistant Professor, Neurology, University of Florida; Mugilan Mugilan Poongkunran, MD – Fellows, Neurointervential, Ochsner Health; Viivek Sabharwal, MD – Assoc Prof, Neuro Critical Care, Cleveland Clinic; Guogen Shan, PhD – Assoc Prof, Neurology, University of Florida; Anil Chimakurthy, MD – Fellows, Neurology, Barrow Neurological
Rationale:
Status epilepticus (SE) results from imbalance between excitatory and inhibitory pathways and failure of physiologic seizure cessation mechanisms. Animal studies have shown very high glutamate levels in status epilepticus (SE). Vigabatrin (VGB) irreversibly inhibits γ-amino butyric acid-transaminase (GABA-T), increases GABA, and may indirectly lower glutamate levels. Exhaustion of GABAergic pathway, the main inhibitory neurotransmitter, could drive ongoing hyperexcitability in SE. Gamma-vinyl-GABA, or vigabatrin (VGB), is a GABA analogue that irreversibly binds to GABA transaminase and blocks GABA breakdown. We hypothesize that VGB is effective as an adjuvant antiseizure medication (ASM) in refractory SE (RSE) due to its potential to increase GABA availability.
Methods:
A retrospective cohort study of VGB-treated adults with RSE admitted to a single tertiary care center was conducted. After IRB approval, we reviewed charts of patients admitted to the Neuro ICU for management of SRSE between the years of 2014 and 2020. This is a single center, retrospective analysis of cases in which VGB was used as an adjunct treatment. SRSE resolution was defined as successful stopping of anesthetic agents without return epileptic activity on electroencephalogram (EEG).
Results:
Sixty-six patients (mean 58 years, 48.5% males) with RSE were identified. SE was nonconvulsive in 53%, convulsive in 30%, and both in 16.7%. Etiologies were anoxic in 22.7% of the cohort and 66.7% had no prior seizure history. VGB was started on an average on day seven after onset of SE. VGB was given for a mean of 19 days, with a mean maximum daily dose of 3484.9 ± 976.5mg (min 2000mg, max 6000mg). Thirty patients (45.4%) had ongoing SE prior to VGB; all but one (96%; n=29) achieved control with VGB and 19 (63.3%) achieved SE resolution (i.e., tolerated complete wean of anesthetics). Thirty-six patients (54.5%) had controlled SE prior to VGB; resolution of SE was achieved in 25 (69.4%) with VGB. Patients in whom SE was controlled pre-VGB were more likely to have VGB initiated later (mean 11.6±9.3 vs 3. 8±3.8 days after SE onset; p< 0.001). Having a non-anoxic etiology was associated with higher likelihood of favorable VGB response (OR47.7, 95%CI 3.7-1573.3; p=0.009) on logistic regression; however, all 15 anoxic patients achieved SE control with VGB (nine had SE control pre-VGB), and five (33%) tolerated complete wean of anesthetics. Overall, 42 patients (63.6%) survived index hospitalization, of whom 39 (88.6%) had resolution of SE. In the patients with post-anoxic SE, control occurred in all and with resolution in 33%, however, 80% of patients with post-anoxic SE died during hospitalization, most from withdrawal of care.
Conclusions:
In our cohort of patients with super-refractory SE, VGB resulted in control in nearly all patients who had super-refractory SE and resolution in two-thirds of patients. Despite favorable VGB response with control of SE in all patients and four out of five patients with post-anoxic SE did not survive to discharge. Treatment with vigabatrin had a significant beneficial impact on SRSE. Further studies are warranted and it is speculated that earlier treatment with VGB may improve overall outcome.
Funding: None