Isoflurane Use in the Treatment of Super-Refractory Status Epilepticus is Associated with Hippocampal Changes on MRI

Refractory status epilepticus (RSE) is associated with high morbidity and mortality. Experts recommend aggressive management with continuous intravenous infusions or inhaled anesthetics such as isoflurane. However, there is concern that MRI changes in RSE reflect isoflurane neurotoxicity. We performed a case-control study to determine whether isoflurane is neurotoxic, based on MRI signal changes.

We performed a retrospective case-control study of the incidence of MRI changes in RSE treated with and without isoflurane. Charts were reviewed for demographic and treatment information. T1, T2, and FLAIR sequences of MRIs were reviewed independently by two neuroradiologists blinded to treatment group for presence or absence of signal change or atrophy in the meninges, cortex, white matter, basal ganglia, thalamus, hippocampus, brainstem, and cerebellum.

Eight cases of RSE receiving treatment with isoflurane were identified and double-matched with 15 controls who received only intravenous anesthetics. Baseline characteristics were similar. Hippocampal signal change was observed more frequently in cases receiving isoflurane (p = 0.026).

Hippocampal signal changes were associated with isoflurane use in patients with RSE. They were also associated with number of seizure days prior to MRI and the use of multiple anesthetic agents. Similar changes have been seen as a result of RSE itself, and one cannot rule out the possibility these changes represent seizure-related effects. If isoflurane-related, these hippocampal signal changes may be the result of a direct neurotoxic effect of prolonged isoflurane use or failure of isoflurane to protect the hippocampus from seizure-induced injury despite achieving electrographic burst-suppression.