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Clinical course of untreated cerebral cavernous malformations: a meta-analysis of individual patient data

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机构: [1]Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH16 4SB, Midlothian, Scotland; [2]Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland; [3]Mayo Clin, Dept Neurol, Rochester, MN USA; [4]Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA; [5]Toronto Western Hosp, Dept Med Imaging, Toronto, ON M5T 2S8, Canada; [6]Hop Lariboisiere, Hosp Univ DHU NeuroVasc, F-75475 Paris, France; [7]Hallym Univ, Coll Med, Dept Neurosurg, Chunchon, South Korea; [8]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China; [9]Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England; [10]Seoul Natl Univ, Coll Med, Dept Neurosurg, Seoul, South Korea
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Background Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. Methods We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Findings Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15.8%, 95% CI 13.7-17.9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5 . 6, 95% CI 3.2-9.7) and with brainstem CCM location versus other locations (4.4, 2.3-8.6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3.8% (95% CI 2.1-5.5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8.0% (0.1-15.9) for 80 people with brainstem CCM presenting without ICH or FND, 18.4% (13.3-23.5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30.8% (26.3-35.2) for 495 people with brainstem CCM presenting with ICH or FND. Interpretation Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment.

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出版当年[2015]版:
大类 | 1 区 医学
小类 | 1 区 临床神经病学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 临床神经病学
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出版当年[2014]版:
Q1 CLINICAL NEUROLOGY
最新[2023]版:
Q1 CLINICAL NEUROLOGY

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第一作者机构: [1]Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH16 4SB, Midlothian, Scotland;
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通讯机构: [2]Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland;
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