Landscaping evidence on first-line therapies for infantile epileptic spasms syndrome: An umbrella review

Despite numerous systematic reviews/meta-analyses (SR/MAs) have assessed evidence on first-line therapies for infantile epileptic spasms syndrome (IESS), conflict and uncertainty remain about their comparative effectiveness, optimal dosing and combination therapeutic strategies. Therefore, we performed an umbrella review to provide a bird-of-eye view on current evidence, with a dose-stratified synthesis and formal appraisal of evidence.

We included SR/MAs assessing pharmacological and non-pharmacological first-line interventions for new-onset IESS, excluding tuberous sclerosis complex. Primary outcomes were clinical and electroclinical remission within one month of treatment initiation. Four electronic databases were searched from inception to October 2025. Methodological quality and risk of bias were evaluated using AMSTAR-2 and ROBIS. Treatment effects were presented as risk ratios. We assessed review overlap using the corrected covered area (CCA), and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Of 511 full-text articles screened, 20 eligible SRs/Mas (6290 IESS cases) published between 2004 and 2025 were included. Overall overlap was slight (CCA 4.8 %) and most reviews were of low/critically-low quality. Hormonal therapy was superior to vigabatrin (moderate to high certainty evidence), high-dose hormonal therapy outperformed low-dose regimens (moderate certainty), while oral corticosteroids appeared comparable with adrenocorticotropic hormonal therapy (low to very-low certainty evidence). Combination and adjunctive strategies did not demonstrate additional benefit (moderate to low certainity evidence).

Hormonal therapy, particularly at higher doses, remains the most effective first-line treatment for IESS. The predominance of low-quality evidence and short-term outcomes highlights the need for well-designed trials with standardized dosing, etiological stratification, and long-term neurodevelopmental follow-up.