Rationale:
Status epilepticus (SE) results from imbalance between excitatory and inhibitory pathways and failure of physiologic sz cessation mechanisms. Animal studies have shown very high glutamate levels in SE. Vigabatrin (Gamma-vinyl-GABA or 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. VGB is a GABA analogue that irreversibly binds to GABA-T and blocks GABA breakdown. We hypothesize that VGB is effective as an adjuvant antiseizure medication (ASM) in refractory SE due to its potential to increase GABA availability.
Methods:
Retrospective cohort study of VGB-treated adults with RSE admitted to a single tertiary care center. After IRB approval, we reviewed charts of patients admitted to the Neuro ICU for management of SRSE between 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 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 an average on day 7 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.
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 (9 had SE control with anesthetics pre-VGB), and 5 (33%) tolerated complete wean of anesthetics.
Two Outcomes variables were analyzed
1. maximal initial daily dose given (2000 mg, 3000 mg or 4500+)
2. Time delay from onset of SE to treatment by < =48 hrs and >48 hr from SE onset.
No difference was found in outcomes of achieving control of SE for either variable. Overall, 42 patients (63.6%) survived index hospitalization, of whom 39 (88.6%) had resolution of SE. In 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 SRSE, VGB resulted in control in nearly all patients 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 with vigabatrin are warranted and it is speculated that earlier treatment with VGB may improve overall outcome.
Funding: None