Ta Daniel, Ishaque Abdullah H, Elamy Adam, Anand Tanushka, Wu Andrew, Eurich Dean T, Luk Collin, Yang Yee Hong, Kalra Sanjay
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.
Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Eur J Neurol. 2023 May;30(5):1220-1231. doi: 10.1111/ene.15686. Epub 2023 Feb 28.
This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS).
Forty-one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4-month intervals. Texture analysis was performed on T1-weighted magnetic resonance imaging scans and the texture feature 'autocorrelation' was quantified. Whole-brain group-level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region-of-interest and 3D voxel-wise Cox proportional-hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation.
Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional-hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow-up (hazard ratio 1.28, p = 0.005). Similarly, voxel-wise whole-brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan-Meier curve and log-rank tests (χ = 7.402, p = 0.007).
Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials.
本研究旨在评估进行性皮质脊髓束（CST）退变与肌萎缩侧索硬化症（ALS）患者生存率之间的关系。
从加拿大ALS神经影像联盟前瞻性招募了41例ALS患者和42名健康对照者。对参与者进行了间隔4个月的三次连续磁共振成像扫描和临床评估。对T1加权磁共振成像扫描进行纹理分析，并对纹理特征“自相关”进行量化。在患者亚组之间进行全脑组水平比较。使用线性混合模型评估纵向进展。构建感兴趣区域和三维体素的Cox比例风险回归模型用于生存预测。对于所有生存分析，使用第二个独立队列进行模型验证。
双侧CST的自相关在基线时增加，并且在ALS短期存活者中随时间以更快的速度逐渐增加。Cox比例风险回归分析显示，CST的自相关是5年随访生存率的显著预测指标（风险比1.28，p = 0.005）。同样，体素水平的全脑生存分析显示，CST自相关增加与生存期缩短相关。使用CST中位数自相关分层的ALS患者，通过Kaplan-Meier曲线和对数秩检验显示生存时间有显著差异（χ = 7.402，p = 0.007）。
脑退变的严重程度与ALS患者的生存率相关。生存期较短的患者亚组中CST退变进展更快。神经影像有望成为改善患者管理和促进临床试验的工具。
