AES Issues First Evidence-Based Recommendations for Infantile Epilepsy Treatment

The American Epilepsy Society (AES) has published a clinical practice guideline for the management of infantile epilepsy, providing recommendations for pharmacologic, dietary, and surgical treatment in infants and children aged 1 month to <36 months. Published in Epilepsy Currents, the recommendations address a major gap in care for infantile epilepsies outside of infantile spasms and West syndrome, which were excluded because separate treatment guidance already exists.

The guideline was developed by a multidisciplinary panel using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. The panel updated a prior systematic review funded by the Patient-Centered Outcomes Research Institute and conducted by ECRI for the Agency for Healthcare Research and Quality, adding studies published from August 2021 through September 2025. Most recommendations were conditional because of low or very low certainty of evidence, reflecting the limited number and quality of treatment studies in this age group.

Key Recommendations

• Surgery: The panel made strong recommendations for hemispherectomy or hemispherotomy in appropriately selected infants and children with drug-resistant epilepsy due to select hemispheric structural pathologies, including hemimegaloencephaly, Rasmussen encephalitis, Sturge-Weber syndrome, perinatal stroke, and hemispheric cortical dysplasia. The panel also strongly recommended intralobar, multilobar, or focal resections and posterior disconnections for drug-resistant focal or lesional epilepsy.
• Pharmacologic therapy: Conditional recommendations support levetiracetam for new-onset epilepsy, oxcarbazepine rather than levetiracetam for new-onset focal epilepsy, and levetiracetam rather than phenobarbital for new-onset epilepsy. The panel suggested against valproate for new-onset epilepsy of uncertain etiology but supported its use in some cases of drug-resistant epilepsy, with genetic testing recommended before initiation to exclude POLG-related disease.
• Dietary therapy: For drug-resistant epilepsy, the panel suggested ketogenic diet therapy rather than no ketogenic diet and favored classic ketogenic diet approaches in children younger than 24 months. Dietary therapy may also be considered first-line for specific metabolic etiologies, including GLUT1 deficiency and pyruvate dehydrogenase complex deficiency.

The clinical practice guideline includes a treatment algorithm recommending early history, examination, MRI, EEG, and genetic testing to classify infantile epilepsy syndromes. It also highlights the need for timely referral to pediatric epilepsy centers when seizures persist despite initial therapy or when structural or genetic etiologies suggest a role for surgical or dietary treatment.

Source

Freedman D, Babatunde I, Morgan RL, et al. American Epilepsy Society clinical practice guideline: infantile epilepsy. Epilepsy Currents. 2026. doi:10.1177/15357597261433266.