Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T₂-FLAIR or T₂-weighted) and cervical (axial T₂- or T₂*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

中文翻译：

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从大脑到子宫颈脊髓的运动系统中的多发性硬化病变：空间分布及其与残疾的关系。

尽管为解决临床放射学悖论做出了巨大努力，但多发性硬化患者的病灶负荷与身体残疾之间的相关性仍然适中。一种假设可能是皮层脊髓束中的病变位置在解释运动障碍中起关键作用。在这项研究中，我们描述了具有各种疾病表型和残疾状态的患者从皮质到颈脊髓沿皮质脊髓束的病变分布。我们还评估了病变负荷和皮质脊髓束内位置与基线和2年随访期间的残疾之间的联系。我们回顾性分析了来自8个地点的290例患者（22例临床孤立综合征，198例复发缓解，39例继发进行性，31例进行性多发性硬化症）。病变在双脑上均被分割（T₂ -FLAIR或T ₂加权）和子宫颈（轴向T _2-或T ₂*加权）MRI扫描。数据是使用自动且公开可用的管道进行处理的。使用概率图谱来测量病变体积分数，从而确定皮质脊髓束的大脑，脑干和脊髓部分。产生每种表型的病变频率图，并用扩展残疾状况量表评分和锥体功能系统评分评估残疾评分。结果表明，病变沿皮质脊髓束分布不均匀，在电晕辐射中以及C2和C4椎骨水平之间的病变频率最高。在皮质脊髓束的损伤体积分数为在二级和初级渐进患者（平均值= 3.6±2.7％和2.9±2.4％）相比，复发-缓解型患者（1.6±2.1％，均高于P < 0.0001）。按体素分析证实，与复发缓解患者相比，进行性病变的频率更高，在脊髓皮质脊髓束中有明显的双侧丛集（P <  0.01）。基线扩展残疾状况量表评分与脑内病变体积分数（r =  0.31，P <  0.0001），脑干（r =  0.45，P <  0.0001）和脊髓（r =  0.57，P < 0.0001）皮质脊髓束。脊髓皮质脊髓束病变体积分数仍然是多元线性回归模型中最强的因素，与脊髓萎缩无关。基线脊髓皮质脊髓束病变体积分数也与2年随访中的残疾进展有关（P =  0.003）。我们的结果表明，沿大脑，脑干和脊髓部分的皮质脊髓束内病变的累积效应可解释多发性硬化症患者的身体残疾，其中髓内病变的影响最为显着。