Cognitive Dysfunction due to Gelastic Seizures with Hypothalamic Hamartoma

Abstract

Significant evolution in the understanding of epileptic encephalopathy has led to the formalization of "developmental and epileptic encephalopathy (DEE)". Hypothalamic hamartoma produce drug-resistant gelastic seizures, with cognitive dysfunction and behavioral abnormalities (GS-HH: gelastic seizures-hypothalamic hamartoma syndrome). GS-HH, formerly considered as "epileptic encephalopathy", is now classified as DEE. This paper aims to advance scientific understanding of DEE by examining the etiology of GS-HH, the mechanisms of epileptogenesis in HH, and cognitive dysfunction before and after surgical intervention. The etiology of HH is primarily associated with abnormal Sonic Hedgehog (Shh) signaling due to somatic mutations during early embryogenesis. The severity of structural brain abnormalities depends on the timing of these mutations, often resulting in developmental encephalopathy for severe cases. The cellular mechanism underlying epileptogenicity in HH is characterized by aberrant expression of Ca2+-permeable AMPA receptors. Stereotactic radiofrequency thermocoagulation (SRT) is an effective surgical method for controlling gelastic seizures by disconnecting the hypothalamic hamartoma from normal brain. Subsequent improvements in cognitive and behavioral function after SRT indicate a pathological basis for epileptic encephalopathy. Cognitive dysfunction in GS-HH, classified as DEE, is also influenced by a variety of social factors and medication side effects. From a neurodevelopmental perspective, early diagnosis and surgical intervention are crucial.