Infantile epileptic spasms syndrome: Mechanisms and therapeutic approaches

TL;DR

This paper discusses the mechanisms and treatment approaches for infantile epileptic spasms syndrome, a rare form of epilepsy with unique features and limited understanding.

Contribution

The paper highlights unresolved clinical and mechanistic issues in IESS and suggests emerging animal models for better understanding and therapy development.

Findings

IESS has distinct clinical and EEG features but lacks clear neurobiological understanding.

Current therapies are limited to specific drugs not used in other epilepsy syndromes.

New animal models may help uncover IESS pathophysiology and guide future treatments.

Abstract

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.

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