Spinelli Edoardo G, Riva Nilo, Rancoita Paola M V, Schito Paride, Doretti Alberto, Poletti Barbara, Di Serio Clelia, Silani Vincenzo, Filippi Massimo, Agosta Federica
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neuroimage Clin. 2020;27:102315. doi: 10.1016/j.nicl.2020.102315. Epub 2020 Jun 17.
Considering the great heterogeneity of amyotrophic lateral sclerosis (ALS), the identification of accurate prognostic predictors is fundamental for both the clinical practice and the design of treatment trials. This study aimed to explore the progression of clinical and structural brain changes in patients with ALS, and to assess magnetic resonance imaging (MRI) measures of brain damage as predictors of subsequent functional decline.
50 ALS patients underwent clinical evaluations and 3 T MRI scans at regular intervals for a maximum of 2 years (total MRI scans = 164). MRI measures of cortical thickness, as well as diffusion tensor (DT) metrics of microstructural damage along white matter (WM) tracts were obtained. Voxel-wise regression models and longitudinal mixed-effects models were used to test the relationship between clinical decline and baseline and longitudinal MRI features.
The rate of decline of the ALS Functional Rating Scale revised (ALSFRS-r) was significantly associated with the rate of fractional anisotropy (FA) decrease in the body of the corpus callosum (CC). Corticospinal tract (CST) and CC-body alterations had a faster progression in patients with higher baseline ALSFRS-r scores and greater CC-body disruption at baseline. Lower FA of the cerebral peduncle was associated with faster subsequent clinical progression.
In this longitudinal study, we identified a significant association between measures of WM damage of the motor tracts and functional decline in ALS patients. Our data suggest that a multiparametric approach including DT MRI measures of brain damage would provide an optimal method for an accurate stratification of ALS patients into prognostic classes.
鉴于肌萎缩侧索硬化症（ALS）具有高度异质性，确定准确的预后预测指标对于临床实践和治疗试验设计均至关重要。本研究旨在探讨ALS患者临床及脑结构变化的进展情况，并评估脑损伤的磁共振成像（MRI）指标作为后续功能衰退预测指标的价值。
50例ALS患者接受了临床评估，并定期进行3T MRI扫描，最长持续2年（MRI扫描总数=164次）。获取了皮质厚度的MRI测量值以及沿白质（WM）束的微观结构损伤的扩散张量（DT）指标。采用体素回归模型和纵向混合效应模型来检验临床衰退与基线及纵向MRI特征之间的关系。
修订的ALS功能评定量表（ALSFRS-r）的衰退率与胼胝体（CC）体部各向异性分数（FA）的降低率显著相关。皮质脊髓束（CST）和CC体部改变在基线ALSFRS-r评分较高且基线时CC体部破坏较大的患者中进展更快。大脑脚较低的FA与随后更快的临床进展相关。
在这项纵向研究中，我们发现运动束WM损伤指标与ALS患者的功能衰退之间存在显著关联。我们的数据表明，一种包括DT MRI脑损伤测量的多参数方法将为将ALS患者准确分层为预后类别提供一种最佳方法。
