{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:10:10Z","timestamp":1790079010120,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Objectives: Headache is reported in patients with cerebral cavernous malformations (CCMs), yet its prevalence and clinical associations remain poorly characterized. This study aimed to evaluate headache prevalence in children with CCMs and their affected adult relatives and to identify associated clinical, genetic, and neuroimaging associations. Methods: We conducted a cross-sectional study including pediatric patients with CCMs and their affected adult relatives. The occurrence of headache outside the context of acute CCM hemorrhage or surgery was assessed. Headache severity and disability were evaluated using the HIT-6 and MIDAS\/pedMIDAS scales. Results: Of the 66 eligible patients, 63 were included in the final analysis (response rate 95.5%). Median age was 16.03 (range 3\u201366 years), and 29 (46%) had familial CCMs. Headaches were reported by 36 patients (57.1%), with tension-type headache being the most common phenotype (50.0%), followed by migraine (38.9%). Patients with headaches were older than those without headaches (median age 21 vs. 12.2 years, p = 0.008), and adults reported headaches more frequently than children (72.4% vs. 44.1%, p = 0.024). Patients with recurrent headaches were more likely to have presented with acute headache at the time of CCM diagnosis [26\/32 (81.3%) vs. 8\/18 (44.4%), p = 0.007; OR 5.42, 95% CI 1.8\u201319.6]. Headache occurrence was not associated with sex, genetic diagnosis, epilepsy, lesion number, or location. Hyperintense T1-weighted MRI signal within CCM lesions was associated with severe, disabling headache (MIDAS grade IV;6\/12 [50%] vs. 0\/7, p = 0.044). Conclusions: Headaches are common among patients with CCMs and increase with age regardless of lesion number and location. T1-weighted MRI hyperintensity within CCMs was associated with severe headache-related disability in adults. Headache in adult relatives may serve as a clinical clue to familial CCM carrier status. These findings require confirmation in larger studies.<\/jats:p>","DOI":"10.3390\/jcm15187267","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"7267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Headache in Cerebral Cavernous Malformations: Clinical, Genetic, and Neuroimaging Associations"],"prefix":"10.3390","volume":"15","author":[{"given":"Tamar","family":"Shiran","sequence":"first","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Daniel","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Shelly I.","family":"Shiran","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Radiology, Pediatric Radiology Unit, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Libzon","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Institute, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"},{"name":"Department of Physical Therapy, School of Health Professions, Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Jonathan","family":"Roth","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Pediatric Neurosurgery Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel"},{"name":"The Pediatric Brain Center, Dana-Dwek Children\u2019s Hospital, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Shlomi","family":"Constantini","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Pediatric Neurosurgery Department, Tel Aviv Medical Center, Tel Aviv 6423906, Israel"},{"name":"The Pediatric Brain Center, Dana-Dwek Children\u2019s Hospital, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Amnon","family":"Mosek","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Neurology, The Headache Clinic, Tel Aviv Medical Center, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5315-3738","authenticated-orcid":false,"given":"Moran","family":"Hausman-Kedem","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Pediatrics, Dana-Dwek Children\u2019s Hospital, Tel Aviv Sourasky University Medical Center, Tel Aviv 6423906, Israel"},{"name":"The Pediatric Brain Center, Dana-Dwek Children\u2019s Hospital, Tel Aviv 6423906, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1161\/STROKEAHA.108.515544","article-title":"Hemorrhage from cavernous malformations of the brain: Definition and reporting standards. 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