Ryu Wi-Sun, Woo Sung-Ho, Schellingerhout Dawid, Jang Min Uk, Park Kyoung-Jong, Hong Keun-Sik, Jeong Sang-Wuk, Na Jeong-Yong, Cho Ki-Hyun, Kim Joon-Tae, Kim Beom Joon, Han Moon-Ku, Lee Jun, Cha Jae-Kwan, Kim Dae-Hyun, Lee Soo Joo, Ko Youngchai, Cho Yong-Jin, Lee Byung-Chul, Yu Kyung-Ho, Oh Mi Sun, Park Jong-Moo, Kang Kyusik, Lee Kyung Bok, Park Tai Hwan, Lee Juneyoung, Choi Heung-Kook, Lee Kiwon, Bae Hee-Joon, Kim Dong-Eog
1 Stroke Centre and Korean Brain MRI Data Centre, Dongguk University Ilsan Hospital, Korea.
2 Departments of Radiology and Cancer Systems Imaging, University of Texas M. D. Anderson Cancer Centre, USA.
Brain. 2017 Jan;140(1):158-170. doi: 10.1093/brain/aww259. Epub 2016 Dec 22.
Leukoaraiosis or white matter hyperintensities are frequently observed on magnetic resonance imaging of stroke patients. We investigated how white matter hyperintensity volumes affect stroke outcomes, generally and by subtype. In total, 5035 acute ischaemic stroke patients were enrolled. Strokes were classified as large artery atherosclerosis, small vessel occlusion, or cardioembolism. White matter hyperintensity volumes were stratified into quintiles. Mean age (± standard deviation) was 66.3 ± 12.8, 59.6% male. Median (interquartile range) modified Rankin Scale score was 2 (1-3) at discharge and 1 (0-3) at 3 months; 16.5% experienced early neurological deterioration, and 3.3% recurrent stroke. The Cochran-Mantel-Haenszel test with adjustment for age, stroke severity, sex, and thrombolysis status showed that the distributions of 3-month modified Rankin Scale scores differed across white matter hyperintensity quintiles (P < 0.001). Multiple ordinal logistic regression analysis showed that higher white matter hyperintensity quintiles were independently associated with worse 3-month modified Rankin Scale scores; adjusted odds ratios (95% confidence interval) for the second to fifth quintiles versus the first quintile were 1.29 (1.10-1.52), 1.40 (1.18-1.66), 1.69 (1.42-2.02) and 2.03 (1.69-2.43), respectively. For large artery atherosclerosis (39.0%), outcomes varied by white matter hyperintensity volume (P = 0.01, Cochran-Mantel-Haenszel test), and the upper three white matter hyperintensity quintiles (versus the first quintile) had worse 3-month modified Rankin Scale scores; adjusted odds ratios were 1.45 (1.10-1.90), 1.86 (1.41-2.47), and 1.89 (1.41-2.54), respectively. Patients with large artery atherosclerosis were vulnerable to early neurological deterioration (19.4%), and the top two white matter hyperintensity quintiles were more vulnerable still: 23.5% and 22.3%. Moreover, higher white matter hyperintensities were associated with poor modified Rankin Scale improvement: adjusted odds ratios for the upper two quintiles versus the first quintile were 0.66 (0.47-0.94) and 0.62 (0.43-0.89), respectively. For small vessel occlusion (17.8%), outcomes tended to vary by white matter hyperintensitiy volume (P = 0.10, Cochran-Mantel-Haenszel test), and the highest quintile was associated with worse 3-month modified Rankin Scale scores: adjusted odds ratio for the fifth quintile versus first quintile, 1.98 (1.23-3.18). In this subtype, worse white matter hyperintensities were associated with worse National Institute of Health Stroke Scale scores at presentation. For cardioembolism (20.6%), outcomes did not vary significantly by white matter hyperintensity volume (P = 0.19, Cochran-Mantel-Haenszel test); however, the adjusted odds ratio for the highest versus lowest quintiles was 1.62 (1.09-2.40). Regardless of stroke subtype, white matter hyperintensities were not associated with stroke recurrence within 3 months of follow-up. In conclusion, white matter hyperintensity volume independently correlates with stroke outcomes in acute ischaemic stroke. There are some suggestions that stroke outcomes may be affected by leukoaraiosis differentially depending on stroke subtypes, to be confirmed in future investigations.
脑白质疏松症或白质高信号在中风患者的磁共振成像中经常被观察到。我们研究了白质高信号体积如何总体上以及按亚型影响中风预后。总共纳入了5035例急性缺血性中风患者。中风被分类为大动脉粥样硬化、小血管闭塞或心源性栓塞。白质高信号体积被分为五个五分位数。平均年龄（±标准差）为66.3±12.8岁，男性占59.6%。出院时改良Rankin量表评分的中位数（四分位间距）为2（1 - 3），3个月时为1（0 - 3）；16.5%的患者经历了早期神经功能恶化，3.3%的患者发生了复发性中风。经年龄、中风严重程度、性别和溶栓状态调整后的Cochran - Mantel - Haenszel检验显示，3个月改良Rankin量表评分的分布在白质高信号五分位数之间存在差异（P < 0.001）。多序贯逻辑回归分析表明，较高的白质高信号五分位数与3个月时较差的改良Rankin量表评分独立相关；第二至第五五分位数与第一五分位数相比的调整优势比（95%置信区间）分别为1.29（1.10 - 1.52）、1.40（1.18 - 1.66）、1.69（1.42 - 2.02）和2.03（1.69 - 2.43）。对于大动脉粥样硬化（39.0%），预后因白质高信号体积而异（P = 0.01，Cochran - Mantel - Haenszel检验），白质高信号最高的三个五分位数（与第一五分位数相比）3个月时改良Rankin量表评分更差；调整后的优势比分别为1.45（1.10 - 1.90）、1.86（1.41 - 2.47）和1.89（1.41 - 2.54）。大动脉粥样硬化患者易发生早期神经功能恶化（19.4%），白质高信号最高的两个五分位数患者更易发生：分别为23.5%和22.3%。此外，较高的白质高信号与改良Rankin量表改善不佳相关：最高的两个五分位数与第一五分位数相比的调整优势比分别为0.66（0.47 - 0.94）和0.62（0.43 - 0.89）。对于小血管闭塞（17.8%），预后倾向于因白质高信号体积而异（P = 0.10，Cochran - Mantel - Haenszel检验），最高五分位数与3个月时较差的改良Rankin量表评分相关：第五五分位数与第一五分位数相比的调整优势比为1.98（1.23 - 3.18）。在该亚型中，更严重的白质高信号与发病时较差的美国国立卫生研究院卒中量表评分相关。对于心源性栓塞（20.6%），预后在白质高信号体积方面无显著差异（P = 0.19，Cochran - Mantel - Haenszel检验）；然而，最高五分位数与最低五分位数相比的调整优势比为1.62（1.09 - 2.40）。无论中风亚型如何，白质高信号与随访3个月内的中风复发均无关。总之，白质高信号体积与急性缺血性中风的预后独立相关。有一些迹象表明，中风预后可能因脑白质疏松症而根据中风亚型受到不同影响，有待未来研究证实。
