Infantile spasms are etiologically heterogeneous, arising from a broad spectrum of structural, genetic, metabolic, immune, and unknown causes. Structural causes include brain malformations, hypoxic-ischemic encephalopathy, cortical dysplasias, and tuberous sclerosis complex. The genetic landscape encompasses numerous distinct developmental and epileptic encephalopathy (DEE) subtypes that manifest with the infantile spasms phenotype; recognized subtypes include developmental and epileptic encephalopathy types 1, 2, 5, 12, 15, 27, 30, and 40. Each of these subtypes represents a genetically and clinically distinct condition contributing to the broader infantile spasms syndrome classification. Metabolic disorders affecting brain energy metabolism, amino acid pathways, or neurotransmitter synthesis also account for a meaningful subset of cases. In a portion of affected infants, comprehensive evaluation does not identify an underlying cause. The etiologic classification has direct implications for prognosis, recurrence risk assessment, and selection of treatment approaches.

Diagnosis of infantile spasms is based on recognition of the clinical triad—epileptic spasms, hypsarrhythmia on EEG, and developmental regression—in an infant of characteristic age. The EEG is central to the diagnostic process; hypsarrhythmia is a highly characteristic pattern that, when present, strongly supports the diagnosis. Not all infants display the full triad simultaneously, and EEG patterns may be absent or atypical during early stages. Comprehensive etiologic evaluation typically includes neuroimaging to assess for structural brain abnormalities and metabolic and genetic testing to identify an underlying cause, given the prevalence of identifiable etiologies across the syndrome. Etiologic identification informs prognostic counseling and guides treatment selection across the heterogeneous population of affected infants.

Three medications carry FDA approval for the treatment of infantile spasms. Repository corticotropin injection, marketed as H.P. Acthar Gel, is an adrenocorticotropic hormone preparation with approval for this indication. Vigabatrin, a gamma-aminobutyric acid transaminase inhibitor, is approved in two formulations: Sabril, approved in 2009, and Vigafyde, approved in 2024. Beyond these approved agents, several compounds have received FDA orphan drug designation for infantile spasms—including cannabidiol (two separate sponsor designations), cosyntropin, ganaxolone, tricaprilin, a combined vigabatrin and cosyntropin formulation, and additional investigational compounds. Orphan drug designation signals regulatory recognition of the condition's rarity and provides drug development incentives but does not confer approval status. Nonpharmacologic approaches including the ketogenic diet are under active clinical investigation. Current trials also explore combination pharmacotherapy and bioelectronic monitoring strategies for children with epileptic encephalopathies.

Prognosis in infantile spasms is highly variable and closely tied to the underlying etiology. Infants with an identifiable structural or genetic cause generally face a less favorable developmental trajectory, with many experiencing persistent epilepsy and intellectual disability. Those in whom no underlying cause is identified have historically fared somewhat better on average, though adverse outcomes remain common across all etiologic groups. Developmental regression that occurs during the period of active spasms may partially reverse following effective seizure control, but full recovery of lost milestones is uncommon. Long-term neurodevelopmental outcomes vary substantially across the spectrum of etiologic subgroups that fall under the infantile spasms classification, and the heterogeneity of the syndrome makes population-level prognosis statements difficult to apply to individual cases.

Infantile spasms are the subject of active investigation, with nine clinical trials currently registered. Among recruiting studies, a Phase 1 trial (NCT06700811) is examining the ketogenic diet for prevention of epileptic spasms in infantile-onset genetic epilepsies, and a Phase 2 trial (NCT04289467) is investigating fenfluramine for refractory infantile spasms. A comparative trial (NCT04302116) is evaluating vigabatrin with high-dose prednisolone combination therapy against vigabatrin alone. A study coordinated by the Telethon Kids Institute (NCT07585643) is examining EEG monitoring reliability in children with developmental and epileptic encephalopathies. The published literature includes 214 classified publications, with case reports and case series representing the largest category at 58 publications, followed by 35 review articles. The research landscape also includes contributions from biomarker research and gene therapy-adjacent investigations, with academic institutions constituting the primary sponsoring profile for current research efforts.