Upper Cervical Cord Area as a Biomarker of Conversion to Secondary Progressive Multiple Sclerosis

OBJECTIVE: This study assessed whether upper cervical cord area (UCCA) measured on routine brain MRI can serve as a biomarker of conversion to SPMS. METHODS: This is a single-center retrospective cohort study of RRMS patients with cross-sectional and longitudinal analyses of clinical and MRI data. Future SPMS converters were matched by age, sex, and disease duration with non-converters. UCCA at C1-C3 was measured at a pre-conversion visit in converters and at the first available visit in non-converters. Analysis was performed using Pearson's correlation and multivariable logistic regression. Longitudinal analyses included patients with ≥ 6 months MRI interval (mean follow-up 3.38 ± 1.88 years). RESULTS: 97 patients (32 converters, 65 non-converters) were included. Cross-sectionally, reduced C2 and C3 area was associated with conversion (C2: OR 1.09, p = 0.01; C3: OR 1.09, p = 0.014). Lower UCCA correlated with higher EDSS (C2: r = -0.496, p < 0.001), worse T25-FWT (C2: r = -0.388, p < 0.001) and 9-HPT (C2: r = -0.312, p = 0.003), and reduced white matter and thalamic volumes (p ≤ 0.006). Longitudinal analysis (n = 50; 16 converters, 34 non-converters) demonstrated atrophy in converters at C1, C2 and C3 (C1: OR 1.70, p = 0.014; C2: OR 1.74, p = 0.003; C3: OR 1.75, p = 0.002), with mean annual percent reductions of 5.0%, 5.2%, and 6.0%, respectively. INTERPRETATION: Reduced UCCA and accelerated upper cervical cord atrophy were associated with conversion to SPMS and worsening disability, supporting UCCA as an accessible imaging biomarker of MS progression.