The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage with cerebral amyloid angiopathy: model development and diagnostic test accuracy study
The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage with cerebral amyloid angiopathy: model development and diagnostic test accuracy study
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脑叶出血伴脑淀粉样血管病的爱丁堡 CT 和遗传诊断标准：模型开发和诊断测试准确性研究
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发表时间：
2018
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通讯作者：
C. Humphreys
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作者：
C. Humphreys
摘要背景与脑淀粉样血管病（CAA）相关的自发性脑叶内出血的识别是重要的，因为它与脑内出血复发的风险比动脉硬化相关的脑内出血更高。我们的目的是建立一个预测模型，利用CT特征和基因型识别CAA相关脑叶出血。方法：我们确定了经CT诊断为首次脑内出血的成年人，他们死亡并进行了研究性尸检，作为Lothian脑内出血、病理学、成像和神经学结局（LINCHPIN）研究的一部分，这是一项前瞻性、基于人群的初始队列研究。我们确定了APOE基因型，放射科医生对CT影像学表现进行了评分。放射科医生不知道临床，遗传和组织病理学特征。一名神经病理学家对脑组织进行小血管疾病（包括CAA）的评级，并对临床、影像学和遗传特征进行掩蔽。我们在逻辑回归模型中使用CT和APOE基因型数据，我们使用Bootstrapping进行内部验证，以预测CAA相关脑叶内出血的风险，得出诊断标准，并估计诊断准确性。结果在62例（56%）参与者中为肺叶，41例（37%）为深部，7例（6%）为幕下。在62例脑叶内出血的参与者中，36例（58%）与中度或重度CAA相关，而26例（42%）与无CAA或轻度CAA相关，并且与蛛网膜下腔出血独立相关（32/36例[89%] vs 11/26例[42%]; p=0·014），脑内出血伴指状突起（36例患者中14例[39%] vs 0; p= 0.043）和APOE ε4携带（36例患者中18例[50%] vs 26例患者中2例[8%]; p= 0.0020）。使用这三个变量的CAA相关脑叶内出血预测模型具有极好的区分度（c统计量0.92，95%CI 0.86 - 0.98），并经内部验证证实。对于排除标准，蛛网膜下腔出血或APOE ε4携带均没有100%的敏感性（95% CI 88-100）。对于纳入标准，蛛网膜下腔出血和APOE ε4占有或指状突起具有96%的特异性（95% CI 78-100）。CAA相关脑叶内出血的CT和APOE基因型预测模型在该队列中显示出良好的区分力，但需要外部验证。爱丁堡纳入和排除诊断标准可能会告知预后和治疗决策，取决于CAA相关脑叶内出血的识别。
Summary Background Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype. Methods We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy. Findings was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ε4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86–0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ε4 possession had 100% sensitivity (95% CI 88–100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ε4 possession or finger-like projections had 96% specificity (95% CI 78–100). Interpretation The CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.