Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability

Abstract

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.

Axonal loss in major sensorimotor tracts is associated with impaired motor performance in minimally disabled multiple sclerosis patients

“…We observed moderate correlations (not significant at an FDR corrected level) between CST FC and whole-brain lesion load, S1 atrophy and thalamic atrophy, but no correlation with cervical cord lesion load or cross-sectional area where most CST tracts terminate 29 and lesions are commonly located. 30 Consistent with recent reports, 31 we observed relatively little primary lesion activity was present within CST, so axonal loss within these tracts could be attributable to spinal cord lesions or trans-synaptic degeneration due to lesions in second-order tracts. While we did not see a correlation with cervical cord lesion volume, these results must be interpreted with caution as we could only identify lesions within the rostral segments (C1–C4) due to a lack of dedicated spinal cord imaging consistently acquired during routine monitoring scans.…”

Prognostic Accuracy of NEDA-3 in Long-term Outcomes of Multiple Sclerosis

“… 39 Our finding is in line with this latter evidence because the damage of long neural pathways, representing functional “bottlenecks” (including the efferent corticospinal tracts for movement), resulted to be associated with neurologic impairment and long-term disability. 40 …”

The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage

“…An additional ROI was drawn on the cerebrospinal fluid as reference. Signal intensity measurements (SI) were focused on structures frequently involved in MS, such as the medial longitudinal fasciculus, the trigeminal tract, as well as corticospinal pyramids [22][23][24][25][26][27].…”