title: Mechanisms of intrinsic epileptogenesis in human gelastic seizures with hypothalamic hamartoma.
abstract: Human hypothalamic hamartoma (HH) is a rare developmental malformation often characterized by gelastic seizures, which are refractory to medical therapy. Ictal EEG recordings from the HH have demonstrated that the epileptic source of gelastic seizures lies within the HH lesion itself. Recent advances in surgical techniques targeting HH have led to dramatic improvements in seizure control, which further supports the hypothesis that gelastic seizures originate within the HH. However, the basic cellular and molecular mechanisms of epileptogenesis in this subcortical lesion are poorly understood. Since 2003, Barrow Neurological Institute has maintained a multidisciplinary clinical program to evaluate and treat patients with HH. This program has provided a unique opportunity to investigate the basic mechanisms of epileptogenesis using surgically resected HH tissue. The first report on the electrophysiological properties of HH neurons was published in 2005. Since then, ongoing research has provided additional insights into the mechanisms by which HH generate seizure activity. In this review, we summarize this progress and propose a cellular model that suggests that GABA-mediated excitation contributes to epileptogenesis in HH lesions.
authors.affiliation: Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA; Department of Physiology, Shantou University of Medical College, Shantou, Guangdong, China; Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Shen
authors.forename: Shen-Feng
authors.initials: SF
authors.lastname: Qiu
authors.forename: John F
authors.initials: JF
authors.lastname: Kerrigan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D004828:Epilepsies, Partial / Q000150:complications* / Q000473:pathology*; D006222:Hamartoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007027:Hypothalamic Diseases / Q000378:metabolism* / Q000473:pathology*; D009415:Nerve Net / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: Epileptogenesis; Gelastic seizures; Human hypothalamic hamartoma