Clinical features associated with a response to ethosuximide in developmental and epileptic encephalopathy with spike wave activation in sleep

Developmental and epileptic encephalopathy with spike-wave activation in sleep (D)EE-SWAS is characterized by a marked increase in epileptiform activity during non-REM sleep. This increase in sleep-related epileptic activity disturbs normal sleep architecture and leads to a stagnation and regression in various behavior and neurocognitive domains. Ethosuximide (ETX) targets T-type calcium channel in the thalamus, an area involved in the generation of sleep potentials and sleep-activated spikes, and as such, ETX had been tried in the past for (D)EE-SWAS. In this retrospective study, we reviewed our database for patients with (D)EE-SWAS-spectrum disorders treated with ETX. Among patients treated with ETX as an add-on therapy, 43.5% (10/23) achieved an absolute decrease in spike-wave index (SWI%) of 25 or more (ETX responder) at the first follow-up EEG compared to baseline; whereas 57.1% (12/21) were ETX responders at the second follow-up EEG. Statistical testing showed that ETX responder status was significantly associated with several clinical factors, including underlying etiology, focal interictal epileptiform discharges, and epilepsy syndrome. A trend towards an association of ETX responder and normal MRI was seen but did not reach statistical significance. Overall, our data supports the use of ETX in (D)EE-SWAS, and that it is possible to predict ETX responders based on clinical factors.