Electroclinical and behavioral outcomes of add-on ethosuximide in children with developmental and epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS): A prospective observational study.

OBJECTIVE

To evaluate the electroclinical and behavioral outcomes, and tolerability of add-on ethosuximide in children with developmental and epileptic encephalopathy with spike-wave activation in sleep (D/EE-SWAS) and to identify predictors of treatment response.

METHODS

This prospective, single-center, observational cohort study included children aged 4-18 years with D/EE-SWAS receiving add-on ethosuximide at a tertiary pediatric neurology center. Seizure outcomes, electroencephalographic (EEG) response based on spike-wave index (SWI), parent-reported language and cognitive outcomes, behavioral outcomes using the Strengths and Difficulties Questionnaire (SDQ), and adverse effects were assessed following treatment. Outcomes were compared between idiopathic and structural etiologies. Predictors of seizure and EEG response were explored using univariate and multivariable analyses.

RESULTS

Thirty-nine children were included (56% structural and 44% idiopathic etiologies). The median age at diagnosis of D/EE-SWAS was 6 years (range 1-10 years). Following a median ethosuximide exposure of 14 months, 28/39 (71.8%) achieved seizure freedom and 33/39 (84.6%) demonstrated favorable seizure outcomes. EEG improvement occurred in 29/39 (74.4%), including complete normalization in 8/39 (20.5%). Complete EEG normalization was more frequent in idiopathic compared with structural D/EE-SWAS (41.2%vs 4.5%, p = 0.01). Parent-reported improvement was observed in language (69.2%) and cognition (64.1%). Significant improvement was observed across SDQ domains, including total difficulties, emotional symptoms, hyperactivity, conduct problems, peer problems, and impact scores (all p < 0.001). Longer duration of ethosuximide exposure was associated with favorable seizure outcome, while later epilepsy onset and idiopathic etiology were associated with better EEG response. Adverse effects occurred in 28% and were predominantly mild-to-moderate; one child developed drug reaction with eosinophilia and systemic symptoms.

CONCLUSIONS

Add-on ethosuximide was associated with favorable electroclinical and behavioral outcomes in children with D/EE-SWAS and was generally well tolerated. EEG normalization was more likely in idiopathic disease, while behavioral improvements were observed across etiologic groups. Controlled studies are needed to define the role of ethosuximide within the therapeutic strategy for D/EE-SWAS.