Infantile epileptic spasms syndrome: Mechanisms and therapeutic approaches

Infantile epileptic spasms syndrome (IESS) is a developmental and. epileptic encephalopathy with unique clinical and electrographic features, including seizure semiology (spasms), numerous and diverse etiologies spanning structural, genetic and metabolic causes, characteristic interictal (hypsarrhythmia) and ictal (electrodecrement) electroencephalogram (EEG) patterns, and responsiveness to "standard" pharmacological therapies (adrenocorticotrophic hormone, high-dose corticosteroids, vigabatrin) that are not commonly used in other epilepsy syndromes. Despite these long-recognized clinical features and laboratory investigations using a multiplicity of animal models with different epileptogenic mechanisms, the neurobiological underpinnings of IESS remain poorly understood, hampering the development of alternative treatments. This commentary discusses three aspects of IESS intended to raise fundamental clinical and mechanistic issues to afford greater understanding of the syndrome - nomenclature, EEG findings, and selected emerging animal models that might shed light on IESS pathophysiology and guide therapy development.