From the Department of Neurology (A.S.D., E.G., A.B., R.W.R., A.A.F., A.V., L.H.S., J.R., S.M.G., M.E.G.), Massachusetts General Hospital, Department of Neurology (A.S.D.), Beth Israel Deaconess Medical Center, and Henry and Allison McCance Center for Brain Health (A.B., J.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Centre Hospitalier (M.P.), Université de Tours, France; and Department of Emergency Medicine (J.G.), Massachusetts General Hospital, Harvard Medical School, Boston.
Neurology. 2023 Aug 8;101(6):e636-e644. doi: 10.1212/WNL.0000000000207476. Epub 2023 Jun 8.
Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA.
Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[-]) in univariate and multivariable models.
Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(-). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-) (34% vs 59%, = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, < 0.01) and severe CSO-EPVS (33% vs 11%, < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00-1.07, = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19-0.89, = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63-16.94, = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78-10.13, < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38-11.38, < 0.01) compared with that in patients with mixed ICH/cSS(-).
The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(-) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.
高血压性脑小血管病（HTN-cSVD）是合并皮质下脑微出血（CMBs）和脑实质内出血（ICH）的患者中主要的微血管病变。我们假设脑淀粉样血管病（CAA）也是伴有皮质表面铁沉积（cSS）的混合 ICH 患者的一种促发微血管病变，cSS 与 CAA 密切相关。
回顾性分析了连续入住转诊中心的非外伤性 ICH 患者前瞻性数据库中的脑 MRI，以评估 CMBs、cSS 和非出血性 CAA 标志物（皮质下腔隙、脑桥中央髓鞘溶解症扩大的血管周围间隙[CSO-EPVS]和多灶性脑白质高信号[WMH]模式）的存在情况。在单变量和多变量模型中，比较了伴有和不伴有 cSS 的混合 ICH 患者（混合 ICH/cSS[+]和混合 ICH/cSS[-]）之间 CAA 标志物和左心室肥厚（LVH）的频率，LVH 是高血压终末器官损伤的标志物。
在 1791 例 ICH 患者中，有 40 例为混合 ICH/cSS[+]，256 例为混合 ICH/cSS[-]。与混合 ICH/cSS[-]患者相比，混合 ICH/cSS[+]患者的 LVH 更为少见（34% vs 59%， = 0.01）。与混合 ICH/cSS[-]患者相比，混合 ICH/cSS[+]患者的 CAA 影像学标志物更为常见，包括多灶性 WMH 模式（18% vs 4%， < 0.01）和严重的 CSO-EPVS（33% vs 11%， < 0.01）。在逻辑回归模型中，年龄较大（校正后每增加 1 岁的比值比[aOR]为 1.04，95%CI 为 1.00-1.07， = 0.04）、缺乏 LVH（aOR 为 0.41，95%CI 为 0.19-0.89， = 0.02）、多灶性 WMH 模式（aOR 为 5.25，95%CI 为 1.63-16.94， = 0.01）和严重的 CSO-EPVS（aOR 为 4.24，95%CI 为 1.78-10.13， < 0.01）与混合 ICH/cSS[+]独立相关，进一步调整了高血压和冠心病后。在 ICH 幸存者中，与混合 ICH/cSS[-]患者相比，混合 ICH/cSS[+]患者的 ICH 复发的调整后的危险比为 4.65（95%CI 为 1.38-11.38， < 0.01）。
混合 ICH/cSS[+]的潜在微血管病变可能包括 HTN-cSVD 和 CAA，而混合 ICH/cSS[-]可能主要由 HTN-cSVD 驱动。这些基于影像学的分类方法对于分层 ICH 风险可能很重要，但需要在纳入先进影像学/病理学的研究中进一步证实。
