Yazdanian Taravat, Azimi Parisa, Babu Suma
Sean M Healey & AMG Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Neurosurgery, Alborz University of Medical Sciences, Karaj, Iran; Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neuroimage Clin. 2025 Jun 26;47:103832. doi: 10.1016/j.nicl.2025.103832.
Disease tracking and prognostication of amyotrophic lateral sclerosis (ALS) can be quite challenging in people living with ALS, due to the complexity of central nervous system disease biology. This systematic review and meta-analysis aim to summarize cervical spinal cord quantitative MRI (qMRI) biomarker changes in individuals with ALS.
PubMed, Scopus, Cochrane Library, and Web of Science databases were searched up to August 2023. The terms used were "ALS", "cervical spinal cord", "MRI"," diffusion tensor imaging (DTI)", " fractional anisotropy (FA)", " mean diffusivity (MD) "," magnetization transfer ratio (MTR)", " cross-sectional area (CSA)", " radial diffusivity (RD) ", and " atrophy ". The Newcastle-Ottawa scale (NOS) was used to assess study quality. We calculated the pooled: 1) Standardized mean difference (SMD) and 95% CIs for comparative assessment of qMRI parameters in ALS individuals and the healthy population. 2) Estimate the mean of qMRI parameters for normative values in two groups by CMA software. Heterogeneity and publication bias were determined by the I-squared statistic and funnel plots.
Thirty studies, with 1817 participants (35.9 % female) were included in this review, and 29 had a NOS ≥ 5 which indicates high-quality of data overall. The SMD analysis showed (a) significant decrease in CSA along the whole length of cervical cord (C1-C7) (p value < 0.0001), with a preferential thinning of the cervical enlargement region (C4-C6 region) (p value < 0.0001) (b) significant decrease in FA (p value < 0.0001), particularly FA left lateral corticospinal tract (p value < 0.0001) and (c) a significant increase in MD (p value < 0.0001) in ALS individuals compared to controls. The pooled analysis reveals that the mean (SD) values for ALS individuals versus controls for (a) CSA (in mm) were C1 [73.4 (0.75), 78.5 (0.67), 6.9 % difference]; C2 [70.6 (3.1), 71.5 (3.5), 1.2 % difference]; C3 [69.8(1.5), 74.9 (1.9), 7.3 % difference]; C4 [71.9 (1.8), 77.6 (2.8), 7.9 % difference]; C5 [71.8 (2.5), 79.5 (3.3), 10.7 % difference]; C6 [66.8 (2.7), 73.7 (3.7), 10.3 % difference]; C7 [56.7 (F2.2), 62.1 (2.5), 9.5 % difference]; (b) FA [0.54 (0.03), 0.56 (0.03)]; (c) MD[1.11 (0.18), 0.88(0)]; and (d) FA LLCST [ 0.65 (0.04), 0.77 (0.04)], respectively. The mean (SD) value of the MTR and RD for ALS individuals was 40.3 (2.3), and 0.70 (0.0).
qMRI metrics of spinal cord show discriminatory potential between ALS and healthy controls. The selective atrophy of the cervical enlargement (C4-C6) is replicable across multiple studies as seen in this metanalysis and hence is a potential imaging marker for quantifying and tracking lower motor neuron degeneration in ALS.
由于中枢神经系统疾病生物学的复杂性，肌萎缩侧索硬化症（ALS）患者的疾病追踪和预后评估颇具挑战性。本系统评价和荟萃分析旨在总结ALS患者颈脊髓定量MRI（qMRI）生物标志物的变化。
检索截至2023年8月的PubMed、Scopus、Cochrane图书馆和Web of Science数据库。使用的检索词为“ALS”、“颈脊髓”、“MRI”、“扩散张量成像（DTI）”、“分数各向异性（FA）”、“平均扩散率（MD）”、“磁化传递率（MTR）”、“横截面积（CSA）”、“径向扩散率（RD）”和“萎缩”。采用纽卡斯尔-渥太华量表（NOS）评估研究质量。我们计算了汇总的：1）标准化均数差（SMD）和95%可信区间，用于比较评估ALS患者和健康人群的qMRI参数。2）通过CMA软件估计两组qMRI参数的规范值均值。通过I²统计量和漏斗图确定异质性和发表偏倚。
本评价纳入了30项研究，共1817名参与者（35.9%为女性），其中29项研究的NOS≥5，表明总体数据质量较高。SMD分析显示：（a）颈髓全长（C1-C7）的CSA显著降低（p值<0.0001），颈膨大区域（C4-C6区域）优先变薄（p值<0.0001）；（b）FA显著降低（p值<0.0001），尤其是左侧皮质脊髓束的FA（p值<0.0001）；（c）与对照组相比，ALS患者的MD显著增加（p值<0.0001）。汇总分析显示，ALS患者与对照组相比，（a）CSA（单位：mm）的均值（标准差）分别为：C1[73.4（0.75），78.5（0.67），差异6.9%]；C2[70.6（3.1），71.5（3.5），差异1.2%]；C3[69.8（1.5），74.9（1.9），差异7.3%]；C4[71.9（1.8），77.6（2.8），差异7.9%]；C5[71.8（2.5）,79.5（3.3），差异10.7%]；C6[66.8（2.7），73.7（3.7），差异10.3%]；C7[56.7（2.2），62.1（2.5），差异9.5%]；（b）FA[0.54（0.03），0.56（0.03）]；（c）MD[1.11（0.18），0.88（0）]；（d）左侧皮质脊髓束FA[0.65（0.04），0.77（0.04）]。ALS患者的MTR和RD的均值（标准差）分别为40.3（2.3）和0.70（0.0）。
脊髓qMRI指标在ALS患者和健康对照之间显示出鉴别潜力。如本荟萃分析所示，颈膨大（C4-C6）的选择性萎缩在多项研究中具有可重复性，因此是量化和追踪ALS患者下运动神经元变性的潜在影像学标志物。
