{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T11:35:32Z","timestamp":1766748932855,"version":"3.40.5"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RCR\u20102022\u201023682289"],"award-info":[{"award-number":["RCR\u20102022\u201023682289"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cardio\u2010facio\u2010cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras\/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical\u2010radiological patterns and discuss the underlying physiopathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic <jats:italic>BRAF<\/jats:italic> variants who experienced SE during a 5\u2010year period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE\/within 72\u2009hours from SE termination in 5\/7 events. Acute\/early post\u2010ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2\/7, focal area of pcASL perfusion change in 2\/7, focal cortical T2\/FLAIR hyperintensity in 2\/7. Follow\u2010up images were available for 4\/7 SE. No acute changes were detected in 2\/7 (MRI performed 4\u2009days after SE termination).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5\/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long\u2010term adverse neurological outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Cardio\u2010facio\u2010cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio\u2010facio\u2010cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio\u2010facio\u2010cutaneous syndrome patients from long\u2010term brain damage.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12864","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T14:34:50Z","timestamp":1699540490000},"page":"258-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Status epilepticus in BRAF\u2010related cardio\u2010facio\u2010cutaneous syndrome: Focus on neuroimaging clues to physiopathology"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-2390","authenticated-orcid":false,"given":"Elisa","family":"Musto","sequence":"first","affiliation":[{"name":"Department of Life Sciences and Public Health Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Neurology, Epilepsy and Movement Disorders, Full member of European Reference Network EpiCARE Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luigia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Perulli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Quintiliani","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Veredice","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Verdolotti","sequence":"additional","affiliation":[{"name":"Radiology and Neuroradiology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Bert\u00e9","sequence":"additional","affiliation":[{"name":"Radiology and Neuroradiology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Leoni","sequence":"additional","affiliation":[{"name":"Center for Rare Disease and Congenital Defects, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Onesimo","sequence":"additional","affiliation":[{"name":"Center for Rare Disease and Congenital Defects, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Maria","family":"Pulitan\u00f2","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Care Unit Trauma Center Pediatric, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Functional Genomics, Ospedale Pediatrico Bambino Ges\u00f9 IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Zampino","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Center for Rare Disease and Congenital Defects, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Contaldo","sequence":"additional","affiliation":[{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenica Immacolata","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"},{"name":"Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013-3189"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20748"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-795-2_27"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1749"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.256"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes12091316"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.04.004"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.05.031"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.012"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2018.10.012"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40635"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2012.12.007"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13121"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr215"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14016"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14499"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01970.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2010.07.019"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2006.10.007"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.001"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2011.07.002"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2017.06.024"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2022.120223"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.08.013"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14493"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15065"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.217.2.r00nv24331"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2015.12.004"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.04014.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17404"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-6111(00)00083-5"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2019.01.024"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-16.1.48"},{"key":"e_1_2_11_35_1","unstructured":"Storia naturale e prognosi delle epilessie in et\u00e0 pediatrica a diversa eziologia: studio a lungo termine. Studio clinico Fondazione Policlinico A. Gemelli IRCCS."},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2018.08.028"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12278"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02175.x"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01646-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.31"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.04.028"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.055772"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-021-02769-w"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/2324709619848816"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-216382"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:48:08Z","timestamp":1707288488000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/epi4.12864"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12864","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"type":"print","value":"2470-9239"},{"type":"electronic","value":"2470-9239"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"assertion":[{"value":"2023-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}