Among patients with (D)EE-SWAS treated with ethosuximide as add-on therapy, 43.5% achieved a clinically meaningful reduction in spike-wave index at first follow-up, and several clinical factors including underlying etiology, focal interictal epileptiform discharges, and epilepsy syndrome were significantly associated with responder status.
Ethosuximide (ETX) achieved a spike-wave index (SWI%) reduction of 25 or more in 43.5% of patients at first follow-up EEG.
The proportion of ETX responders increased to 57.1% at the second follow-up EEG.
ETX responder status was significantly associated with underlying etiology.
ETX responder status was significantly associated with the presence of focal interictal epileptiform discharges.
ETX responder status was significantly associated with epilepsy syndrome classification.
A trend toward association between normal MRI and ETX responder status was observed but did not reach statistical significance.
The authors propose that ETX targets T-type calcium channels in the thalamus as its mechanistic rationale for use in (D)EE-SWAS.
This research suggests that a medication called ethosuximide (ETX), typically used for absence seizures, may be a useful treatment for a serious condition called developmental and epileptic encephalopathy with spike-wave activation in sleep, or (D)EE-SWAS. This condition causes abnormal brain electrical activity to spike dramatically during sleep, disrupting normal sleep and leading to regression or stagnation in behavior and thinking skills in affected children. In this retrospective study of 23 patients, about 43% showed meaningful improvement in their abnormal brain activity at the first follow-up EEG after starting ETX, and this rose to about 57% by the second follow-up EEG, hinting that the drug's benefits may grow over time. Importantly, this research suggests it may be possible to predict which patients are likely to respond to ETX based on identifiable clinical characteristics. Factors such as the underlying cause of the epilepsy, the type of epilepsy syndrome, and whether focal abnormal electrical discharges were present on EEG were all significantly linked to a better response to ETX. There was also a trend suggesting that patients with normal brain MRI scans may respond better, though this finding was not statistically conclusive in this study. The practical implication of this research is that clinicians may be able to use existing clinical information — such as EEG patterns, MRI results, and epilepsy syndrome classification — to identify patients with (D)EE-SWAS who are most likely to benefit from ETX before starting treatment. Because (D)EE-SWAS can cause lasting developmental harm, identifying effective treatments and the patients most likely to respond to them is clinically important. The study's retrospective and relatively small sample size are limitations, and larger prospective studies would be needed to confirm these findings.
Ng A, Warriyar K V V, D'Alfonso S, Scantlebury M. (2026). Clinical features associated with a response to ethosuximide in developmental and epileptic encephalopathy with spike wave activation in sleep.. Epilepsy & behavior : E&B. https://doi.org/10.1016/j.yebeh.2025.110866