Association of the Cervical Canal Area With Disability and Progression in People With Multiple Sclerosis

Background and Objectives In multiple sclerosis (MS), brain reserve serves as a protective factor against cognitive impairment. Previous research has suggested a structural counterpart in the spine—spinal cord reserve—seemed to be associated with physical disability. This study aimed to investigate the potential of the cervical canal area (CCaA) as a proxy for spinal cord reserve in a multicentric cohort of people with MS (PwMS). Methods This retrospective, multicentric, longitudinal study included PwMS and healthy controls (HCs) from 9 European MAGNIMS sites. Baseline cervical 3D T1-weighted images were acquired, excluding poor-quality images. CCaA was estimated independently at the C2/C3 and C3/C4 levels. The Expanded Disability Status Scale (EDSS) score was assessed at baseline and 5-year follow-up. We analyzed mean CCaA differences between groups and the association of CCaA with baseline EDSS scores and disability progression using multivariable regression models adjusted for age, sex, spinal cord parenchymal fraction, and cervical cord lesions. Results After quality check, the cohort included 177 HCs (mean age 39.8 years, 57.6% women) and 428 PwMS (mean age 46.5 years, 60.8% women), comprising 289 people with relapsing MS (PwRMS) and 139 people with progressive MS (PwPMS). No significant differences in CCaA were found between HCs and PwRMS at C2/C3 or C3/C4 levels. Conversely, PwPMS showed a smaller CCaA at the C2/C3 level (210.51 mm2) than HCs (214.62 mm2, estimated mean difference [EMD] −4.11, 95% CI −6.28 to −1.00, p = 0.007) and PwRMS (213.68 mm2, EMD −3.17, 95% CI −5.22 to −0.34, p = 0.026). PwPMS also had a smaller CCaA at C3/C4 (165.16 mm2) than HCs (169.67 mm2, EMD −4.51, 95% CI −5.50 to −1.60, p < 0.001) and PwRMS (169.44 mm2, EMD −3.81, 95% CI −5.22 to −0.34, p < 0.001). At the C3/C4 level, CCaA and baseline EDSS scores were significantly associated (β = −0.13, p < 0.001); in addition, PwMS with clinical worsening at 5-year follow-up displayed a smaller baseline CCaA (worsened vs stable: 167.03 mm2 vs 169.13 mm2, EMD −2.10, 95% CI −3.98 to −023, p = 0.028). Discussion CCaA was associated with baseline EDSS scores and clinical worsening in a multicentric MS cohort, suggesting the existence of spinal cord reserve. PwPMS had a smaller CCaA, indicating that reduced spinal cord reserve might be characteristic of progressive MS. Therefore, spinal cord reserve may represent a novel radiologic marker for better understanding physical disability in MS.