Supplementary Material for: The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage

<b><i>Introduction:</i></b> Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. <b><i>Methods:</i></b> From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. <b><i>Results:</i></b> A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, <i>p</i> &lt; 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, <i>p</i> = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, <i>p</i> &lt; 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, <i>p</i> = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, <i>p</i> = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, <i>p</i> = 0.395). <b><i>Conclusion:</i></b> Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

<b><i>引言：</i></b> 脑内出血（Intracerebral hemorrhage, ICH）是一种毁灭性的出血性事件，常伴随高死亡率或严重神经后遗症。目前对于非脑叶型ICH的血肿部位与年龄相关的差异尚不清楚。本研究旨在阐明年龄与血肿部位之间的关联，并评估不同血肿部位间的小血管疾病（small-vessel disease, SVD）负荷差异，以此作为长期高血压的潜在替代标志物。
<b><i>方法：</i></b> 2014年9月至2019年7月，本研究从一项前瞻性登记库中回顾性纳入连续收治的急性自发性ICH患者。患者于住院期间接受磁共振成像检查，并计算总SVD负荷评分（涵盖微出血、腔隙性梗死、血管周围间隙扩大及脑白质高信号）。采用多因素logistic回归分析评估血肿部位与年龄增长及SVD负荷之间的关联。
<b><i>结果：</i></b> 本研究共纳入444例患者，其中女性156例（占35%）；中位年龄69岁[四分位间距59~79岁]；美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale, NIHSS）评分9[3~17]。多因素logistic回归分析显示，年龄增长与丘脑血肿（每10年年龄增量的比值比[OR]=1.48，95%置信区间[CI]：1.19~1.84，P<0.001）及脑叶血肿（OR=1.58，95%CI：1.19~2.09，P=0.002）独立相关，而与壳核血肿呈独立负相关（OR=0.55，95%CI：0.44~0.68，P<0.001）。即使在校正年龄后，总SVD负荷评分仍与丘脑血肿呈独立正相关（OR=1.27，95%CI：1.01~1.59，P=0.045），与脑叶血肿呈独立负相关（OR=0.74，95%CI：0.55~0.99，P=0.042），但与壳核血肿无显著关联（OR=0.91，95%CI：0.73~1.14，P=0.395）。
<b><i>结论：</i></b> 壳核血肿、丘脑血肿及脑叶血肿均好发于特定年龄及SVD负荷状态：壳核血肿多见于年轻患者，丘脑血肿多见于高龄且SVD负荷较高的患者，而脑叶血肿则多见于高龄且SVD负荷较低的患者。随着年龄增长或SVD负荷加重，不同脑部位的出血易感性存在显著差异。