{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T08:56:42Z","timestamp":1759481802605,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The intrahypothalamic phenotype of hypothalamic hamartomas (HH) is associated with epilepsy, and the parahypothalamic phenotype usually leads to central precocious puberty but not neurological comorbidities or seizures. No study has confirmed the pathological role of parahypothalamic hamartomas in epileptogenesis, and the underlying mechanism is yet to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to investigate whether parahypothalamic hamartomas are intrinsically epileptogenic and elucidate the underlying pathway of epileptogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reviewed 92 patients with HH-related epilepsy, categorized them by the classification system of Delalande and Fohlen, and further classified Type I (corresponding to parahypothalamic HH) into the following three groups based on the relationship between the lesion and mammillary bodies (MB): entirely invaded (Group 1), partially connected (Group 2), and not connected at all (Group 3). We examined different anatomical features with their relationship to clinical manifestations. Stereoelectroencephalography (SEEG) was implanted in both HH and extra-HH cortices in different groups to identify the epileptogenic zone. Corticocortical evoked potentials (CCEPs) were also used to determine the pathological correlation among different regions to determine the related epileptogenic network.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 13 patients presented with parahypothalamic HH and 10 (76.9%) presented with non-GS only, with late-onset age and normal cognitive development, which is different from classical clinical features. SEEG showed that HH is intrinsically epileptogenic in MB-involved parahypothalamic groups. No statistical difference was found in onset age (<jats:italic>p<\/jats:italic>= 0.213), and lesions horizontally oriented from the tuber cinereum without connection to MB were not involved in seizure genesis. CCEP indicated a pathological connection among HH, middle cingulate cortex, and insular cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The parahypothalamic HH can also cause epilepsy and is different from classic HH-related seizures, by non-GS only with the late-onset age and normal cognitive development. MB is proven to be related to non-GS by the mamillo-cingulate-cortex pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.981488","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T06:24:28Z","timestamp":1662963868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Anatomical features decide the atypical seizure manifestation of parahypothalamic hamartomas"],"prefix":"10.3389","volume":"13","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajie","family":"Mo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiu","family":"Shao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"106076","DOI":"10.1016\/j.clineuro.2020.106076","article-title":"Hypothalamic hamartomas: a comprehensive review of the literature - Part 1: Neurobiological features, clinical presentations and advancements in diagnostic tools","volume":"197","author":"Alomari","year":"2020","journal-title":"Clin Neurol Neurosurg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/epi.13752","article-title":"Hypothalamic hamartoma: neuropathology and epileptogenesis","volume":"2","author":"Kerrigan","year":"2017","journal-title":"Epilepsia."},{"key":"B3","first-page":"450","article-title":"Imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases","volume":"25","author":"Freeman","year":"2004","journal-title":"Am J Neuroradiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/epi.13753","article-title":"Clinical features and evolution of the gelastic seizures-hypothalamic hamartoma syndrome","volume":"58","author":"Striano","year":"2017","journal-title":"Epilepsia."},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1111\/j.1528-1167.2009.02125.x","article-title":"The syndrome gelastic seizures-hypothalamic hamartoma: severe, potentially reversible encephalopathy","volume-title":"Epilepsia.","author":"Striano","year":"2009"},{"key":"B6","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/0013-4694(95)00063-5","article-title":"Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study)","volume":"95","author":"Munari","year":"1995","journal-title":"Electroencephalogr Clin Neurophysiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1111\/j.1528-1167.2010.02739.x","article-title":"Ictogenesis and symptomatogenesis of gelastic seizures in hypothalamic hamartomas: an ictal SPECT study","volume":"51","author":"Kameyama","year":"2010","journal-title":"Epilepsia."},{"key":"B8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/epi.13756","article-title":"Hypothalamic hamartoma with epilepsy: review of endocrine comorbidity","volume":"58","author":"Harrison","year":"2017","journal-title":"Epilepsia."},{"key":"B9","doi-asserted-by":"publisher","first-page":"106624","DOI":"10.1016\/j.eplepsyres.2021.106624","article-title":"Epileptic hypothalamic hamartomas impact of topography on clinical presentation and radiosurgical outcome","volume":"173","author":"Hamdi","year":"2021","journal-title":"Epilepsy Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1159\/000308162","article-title":"Central precocious puberty due to hypothalamic hamartomas correlates with anatomic features but not with expression of GnRH, TGFalpha, or KISS1","volume":"73","author":"Chan","year":"2010","journal-title":"Horm Res Paediatr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1212\/WNL.0000000000012773","article-title":"Hypothalamic hamartomas: evolving understanding and management","volume":"97","author":"Cohen","year":"2021","journal-title":"Neurology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3171\/jns.1999.91.2.0212","article-title":"The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma","volume":"91","author":"Arita K","year":"1999","journal-title":"J Neurosurg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/epi.13755","article-title":"Hypothalamic hamartoma: epileptogenesis beyond the lesion?","volume":"58","author":"Scholly","year":"2017","journal-title":"Epilepsia."},{"key":"B14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.seizure.2016.02.013","article-title":"Adult-onset refractory epilepsy with hypothalamic hamartoma and no gelastic seizures successfully treated by stereotactic thermocoagulation: a case report","volume":"37","author":"Sone","year":"2016","journal-title":"Seizure."},{"key":"B15","doi-asserted-by":"publisher","first-page":"450","DOI":"10.3389\/fneur.2018.00450","article-title":"Multimodality image post-processing in detection of extratemporal MRI-negative cortical dysplasia","volume":"9","author":"Hu","year":"2018","journal-title":"Front Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.2176\/nmc.43.61","article-title":"Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification","volume":"43","author":"Delalande","year":"2003","journal-title":"Neurol Med Chir."},{"key":"B17","doi-asserted-by":"publisher","first-page":"107957","DOI":"10.1016\/j.yebeh.2021.107957","article-title":"Stereoelectroencephalography-guided radiofrequency thermocoagulation for hypothalamic hamartoma: electroclinical patterns and the relationship with surgical prognosis","volume":"118","author":"Liu","year":"2021","journal-title":"Epilepsy Behav."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1016\/j.clinph.2020.08.012","article-title":"Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials","volume":"131","author":"Guo","year":"2020","journal-title":"Clin Neurophysiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/epi.12456","article-title":"Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis","volume":"54","author":"Scholly","year":"2013","journal-title":"Epilepsia."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.3760\/cma.j.issn.0366-6999.2011.07.031","article-title":"Temporal lobe epilepsy with hypothalamic hamartoma: a rare case","volume":"124","author":"Yang","year":"2011","journal-title":"Chin Med J."},{"key":"B21","first-page":"309","article-title":"Hamartomas of the tuber cinereum: CT, MR, and pathologic findings","volume":"12","author":"Boyko O","year":"1991","journal-title":"Am J Neuroradiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1227\/00006123-199406000-00001","article-title":"Hypothalamic hamartomas: with special reference to gelastic epilepsy and surgery","volume":"34","author":"Valdueza JM","year":"1994","journal-title":"Neurosurgery."},{"key":"B23","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s00381-006-0139-y","article-title":"Epilepsy related to hypothalamic hamartomas: surgical management with special reference to gamma knife surgery","volume":"22","author":"Regis","year":"2006","journal-title":"Childs Nerv Syst."},{"key":"B24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/epi.13773","article-title":"Achieving a cure for hypothalamic hamartomas: a Sisyphean quest?","volume":"58","author":"Regis","year":"2017","journal-title":"Epilepsia."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1046\/j.1528-1157.2003.04103.x","article-title":"The clinical spectrum of epilepsy in children and adults with hypothalamic hamartoma","volume":"44","author":"Mullatti","year":"2003","journal-title":"Epilepsia."},{"key":"B26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/ane.12209","article-title":"Classification of hypothalamic hamartoma and prognostic factors for surgical outcome","volume":"130","author":"Li","year":"2014","journal-title":"Acta Neurol Scand."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.3171\/2015.4.JNS1582","article-title":"MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas","volume":"124","author":"Kameyama","year":"2016","journal-title":"J Neurosurg."},{"key":"B28","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000048084","article-title":"Hypothalamic hamartoma: comparison of clinical presentation and magnetic resonance images","volume":"56","author":"Debeneix C","year":"2001","journal-title":"Horm Res."},{"key":"B29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1684\/j.1950-6945.2003.tb00014.x","article-title":"From hypothalamic hamartoma to cortex: what can be learnt from depth recordings and stimulation?","volume":"5","author":"Kahane","year":"2003","journal-title":"Epileptic Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.yebeh.2012.02.013","article-title":"The gelastic seizures-hypothalamic hamartoma syndrome: facts, hypotheses, and perspectives","volume":"24","author":"Striano","year":"2012","journal-title":"Epilep Behav."},{"key":"B31","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.spen.2007.03.003","article-title":"Epilepsy in hypothalamic hamartoma: clinical and EEG features","volume":"14","author":"Harvey","year":"2007","journal-title":"Semin Pediatr Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1111\/j.1528-1167.2010.02686.x","article-title":"Semiologic aspects of epileptic seizures in 31 patients with hypothalamic hamartoma","volume":"51","author":"Oehl","year":"2010","journal-title":"Epilepsia."},{"key":"B33","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1212\/01.WNL.0000049457.05670.7D","article-title":"Generalized epilepsy in hypothalamic hamartoma. Evolution and postoperative resolution","volume":"60","author":"Freeman JL","year":"2003","journal-title":"Neurology."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1093\/brain\/awr235","article-title":"Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients","volume":"134","author":"Parvizi","year":"2011","journal-title":"Brain"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.981488\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T17:28:45Z","timestamp":1727976525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2022.981488\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,12]]},"references-count":34,"alternative-id":["10.3389\/fneur.2022.981488"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2022.981488","relation":{},"ISSN":["1664-2295"],"issn-type":[{"type":"electronic","value":"1664-2295"}],"subject":[],"published":{"date-parts":[[2022,9,12]]},"article-number":"981488"}}