Goeldlin Martina B, Fandler-Höfler Simon, Pezzini Alessandro, Manikantan Anusha, Rauch Janis, Hald Stine Munk, Kristensen Mona Løgtholt, Obergottsberger Lena, Sembill Jochen A, Haupenthal David, Larsen Kristin Tveitan, Avramiotis Nikolaos S, Polymeris Alexandros A, Periole Charlotte, Thiankhaw Kitti, Rangus Ida, Puy Laurent, Pasi Marco, Morotti Andrea, Silvestrelli Giorgio, Giacalone Giacomo, Paciaroni Maurizio, Zedde Marialuisa, Giorli Elisa, Tassi Rossana, Delgado-Romeu Marc, Fischer Urs, Volbers Bastian, Hakim Arsany, Z'Graggen Werner J, Nolte Christian H, Werring David J, Raposo Nicolas, Engelter Stefan T, Kristoffersen Espen S, Kuramatsu Joji, Gattringer Thomas, Gaist David, Seiffge David J
Department of Neurology, Inselspital Bern University Hospital and University of Bern, Bern, Switzerland.
Department of Neurology, Medical University of Graz, Graz, Austria.
JAMA Neurol. 2025 Mar 3;82(4):355-63. doi: 10.1001/jamaneurol.2025.0026.
: The spatial and temporal distribution of intracerebral hemorrhage (ICH) recurrence are largely unknown.
To assess timing and location of recurrent ICH events in relation to the index ICH event (adjacent ICH [adjICH] vs remote ICH [remICH]).
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a pooled analysis of individual cohort studies from 2002 to 2021 among hospital-based European cohorts. Patients with 2 or more clinically distinguishable (≥1 recurrent) small vessel disease-related ICH events were included. Data analysis was performed from December 2023 to December 2024.
ICH location and underlying small vessel disease type.
The primary outcome was adjICH, defined by anatomical ICH location and side, and the secondary outcome was time to recurrence. Multivariable regression analyses were conducted adjusting for ICH location, cerebral amyloid angiopathy according to Boston 2.0 or simplified Edinburgh criteria, convexity subarachnoid hemorrhage extension, hypertension, and antihypertensive treatment, including an interaction term for hypertension and antihypertensive treatment.
Among 733 patients (median [IQR] age, 72.4 [65.2 to 79.0] years; 346 female [47.2%]), there were 1616 ICH events, including 733 index and 883 recurrent ICH events (range, 1 to 6 recurrences) over a median (IQR) follow-up of 2.53 (0.66 to 4.92) years. There were 340 patients (46.4%) with adjICH and 393 patients (53.6%) with remICH. Among recurrent ICH events, there were 476 adjICH events and 407 remICH events. In multivariable regression analyses, lobar index ICH (adjusted odds ratio [aOR], 2.08; 95% CI, 1.32 to 3.27) and cerebral amyloid angiopathy at index ICH (aOR, 2.21; 95% CI, 1.57 to 3.11) were associated with higher odds of adjICH, while cerebellar index ICH was associated with lower odds of adjICH (aOR, 0.25; 95% CI, 0.07 to 0.89). The median (IQR) time to recurrence was 1.25 (0.36 to 3.38) years for adjICH and 2.21 (0.66 to 4.85) years for remICH. Previous lobar or convexity subarachnoid hemorrhage (coefficient, -0.75; 95% CI, -1.25 to -0.25; P = .003 ), adjICH (coefficient, -0.60; 95% CI, -1.02 to -0.18; P = .005), and the number of previous ICH events (coefficient per 1-event increase, -0.62; 95% CI, -0.93 to -0.32; P < .001) were independently associated with a shorter time to recurrence.
This study found that early recurrence and cerebral amyloid angiopathy were associated with adjICH. These findings suggest that regional, tissue-based factors may facilitate recurrence and that identifying and targeting local vasculopathic changes may represent potential novel treatment targets.
脑出血（ICH）复发的时空分布在很大程度上尚不清楚。
评估复发性ICH事件相对于首次ICH事件的时间和位置（相邻ICH [adjICH]与远处ICH [remICH]）。
设计、设置和参与者：这项队列研究是对2002年至2021年欧洲医院队列中的个体队列研究进行的汇总分析。纳入了有2次或更多次临床可区分（≥1次复发）的与小血管疾病相关的ICH事件的患者。数据分析于2023年12月至2024年12月进行。
ICH位置和潜在的小血管疾病类型。
主要结局是adjICH，根据ICH的解剖位置和侧别定义，次要结局是复发时间。进行多变量回归分析，对ICH位置、根据波士顿2.0或简化爱丁堡标准的脑淀粉样血管病、脑凸面蛛网膜下腔出血扩展、高血压和降压治疗进行调整，包括高血压和降压治疗的交互项。
在733例患者（中位年龄[四分位间距]，72.4[65.2至79.0]岁；346例女性[47.2%]）中，有1616次ICH事件，包括733次首次ICH事件和883次复发性ICH事件（范围为1至6次复发），中位（四分位间距）随访时间为2.53（0.66至4.92）年。有340例患者（46.4%）发生adjICH，393例患者（53.6%）发生remICH。在复发性ICH事件中，有476次adjICH事件和407次remICH事件。在多变量回归分析中，叶性首次ICH（调整后的优势比[aOR]，2.08；95%置信区间，1.32至3.27）和首次ICH时的脑淀粉样血管病（aOR，2.21；95%置信区间，1.57至3.11）与adjICH的较高几率相关，而小脑首次ICH与adjICH的较低几率相关（aOR，0.25；95%置信区间，0.07至0.89）。adjICH的复发中位（四分位间距）时间为1.25（0.36至3.38）年；remICH为2.21（0.66至4.85）年。既往叶性或脑凸面蛛网膜下腔出血（系数，-0.75；95%置信区间，-1.25至-0.25；P = 0.003）、adjICH（系数，-0.60；95%置信区间，-1.02至-0.18；P = 0.005）以及既往ICH事件的数量（每增加1次事件的系数，-0.62；95%置信区间，-0.93至-0.32；P < 0.001）与较短的复发时间独立相关。
本研究发现早期复发和脑淀粉样血管病与adjICH相关。这些发现表明，基于区域和组织的因素可能促进复发，识别并针对局部血管病变变化可能代表潜在的新治疗靶点。
