Disentangling Age-Related and Disease-Specific Effects on Upper Cervical Cord Area in Patients With Multiple Sclerosis

BACKGROUND AND OBJECTIVES: Cervical cord atrophy is a key predictor of disability and disease progression in multiple sclerosis (MS); however, age-related vs disease-related contributions remain unclear. Here, we investigated whether MS results in a disease-specific reduction in mean upper cervical cord area (MUCCA) beyond aging, and whether this deviation is modulated by sex and age at disease onset. Effects of sex and age at onset (pediatric onset <18, adult onset 18-49, and late onset ≥50 years) were evaluated, along with associations with disability, disease duration, T2 hyperintense lesion, and normalized brain volumes. DISCUSSION: In MS, upper cord atrophy exceeds age-related effects, especially in fifth-sixth decades, and attenuates later as aging effects increase. Disease-specific atrophy is independent of sex. Differences across onset groups largely reflect disease duration. Upper cord atrophy correlates with disability, supporting its role as a sensitive MS-related neurodegeneration biomarker beyond aging.