{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:54:00Z","timestamp":1782266040863,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non\u2010familial multiple cerebral cavernous malformation (CCM) disease over a 5\u2010year period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow\u2010up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non\u2010familial multiple cavernous malformations. Kaplan\u2013Meier and Cox regression analyses were performed to determine the cumulative 5\u2010year risk for hemorrhage and recurrent hemorrhage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non\u2010FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.001) as a predictor for occurrence of recurrent hemorrhage during the 5\u2010year follow\u2010up (FU). The cumulative 5\u2010year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non\u2010FCCM cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5\u2010year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non\u2010FCCM patients showed an equal cumulative 5\u2010year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15253","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T01:50:19Z","timestamp":1642729819000},"page":"1427-1434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non\u2010familial disease"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-5313","authenticated-orcid":false,"given":"Alejandro N.","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Spine Surgery University Hospital Essen  Essen 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