Horne Margaret A, Flemming Kelly D, Su I-Chang, Stapf Christian, Jeon Jin Pyeong, Li Da, Maxwell Susanne S, White Philip, Christianson Teresa J, Agid Ronit, Cho Won-Sang, Oh Chang Wan, Wu Zhen, Zhang Jun-Ting, Kim Jeong Eun, Ter Brugge Karel, Willinsky Robert, Brown Robert D, Murray Gordon D, Al-Shahi Salman Rustam
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Lancet Neurol. 2016 Feb;15(2):166-173. doi: 10.1016/S1474-4422(15)00303-8. Epub 2015 Dec 2.
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.
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.
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.
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.
UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
脑海绵状血管畸形（CCM）可导致有症状的颅内出血（ICH），但其估计风险并不精确，预测因素也仍不确定。我们旨在通过个体患者数据荟萃分析，获得未经治疗的随访期间ICH风险的精确估计值和预测因素。
我们邀请了通过对Ovid MEDLINE和Embase从创刊至2015年4月30日进行系统评价所确定的已发表队列中年龄至少16岁的研究参与者，提供从CCM诊断至首次CCM治疗或最后一次可用随访的临床病程个体患者数据。我们使用生存分析来估计CCM导致的有症状ICH的5年风险（主要结局），使用多变量Cox回归来确定结局的基线预测因素，并使用随机效应模型在荟萃分析中汇总估计值。
在来自六项研究的七个队列的1620人中，204人在5197人年的随访期间发生了ICH（Kaplan-Meier估计5年风险为15.8%，95%CI为13.7%-17.9%）。CCM诊断后5年内ICH的主要结局与有ICH的临床表现或无近期出血脑成像证据的新发局灶性神经功能缺损（FND）与其他表现模式相关（风险比5.6，95%CI为3.2-9.7），与脑干CCM位置与其他位置相关（4.4，2.3-8.6），但年龄、性别和CCM的数量并未增加独立的预后信息。对于718例无ICH或FND表现的非脑干CCM患者，未经治疗的随访期间ICH的5年估计风险为3.8%（95%CI为2.1%-5.5%）；对于80例无ICH或FND表现的脑干CCM患者，为8.0%（0.1%-15.9%）；对于327例有ICH或FND表现的非脑干CCM患者，为18.4%（13.3%-23.5%）；对于495例有ICH或FND表现的脑干CCM患者，为30.8%（26.3%-35.2%）。
临床表现模式和CCM位置与CCM诊断后5年内的ICH独立相关。这些发现可为CCM治疗决策提供参考。
英国医学研究理事会、苏格兰政府首席科学家办公室和英国中风协会。
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