The gelastic seizures-hypothalamic hamartoma syndrome: facts, hypotheses, and perspectives

Abstract

Hypothalamic hamartoma (HH) can be associated with a wide spectrum of epileptic conditions, ranging from a mild form with seizures characterized by urge to laugh and no cognitive involvement up to a catastrophic encephalopathy with early onset gelastic seizures (GS), precocious puberty, and mental retardation. Moreover, a refractory, either focal or generalized, epilepsy develops during the clinical course in nearly all the cases. Neurophysiologic and neuroimaging studies have demonstrated that HH itself generates GS and starts a process of secondary epileptogenesis responsible for refractory focal or generalized epilepsy. The intrinsic epileptogenicity of HH may be explained by the neurophysiological properties of small GABAergic, spontaneously firing HH neurons. Surgical ablation of HH can reverse epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery seem to be useful and safe approaches for treatment, in particular of small HH. Here, we review this topic, based on literature reports and our personal observations. In addition, we discuss pathogenetic hypotheses and suggest new approaches to this intriguing issue.