Upper cervical spinal cord atrophy in MS: Sex, menopause, and neurodegeneration

Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women. Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS). In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCCbrain) was obtained. Impact of sex and menopause on UCCbrain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated. UCCbrain was smaller in pwMS (n = 118, 51.4 ± 5.3 mm2) than controls (n = 118, 54.2 ± 4.4 mm2, p < 0.001) and inversely correlated with older age in pwMS (r = -0.24, p = 0.010) but not in controls (r = -0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCCbrain was smaller in men (49.5 ± 5.9 mm2) than women (51.6 ± 5.5 mm2, p = 0.001), postmenopausal women (49.4 ± 5.6 mm2) than premenopausal women (52.9 ± 4.1 mm2, p < 0.001), and progressive (47.5 ± 5.6 mm2) than relapsing MS (52.1 ± 5.2 mm2, p < 0.001). UCCbrain also correlated with disease duration (r = -0.39, p < 0.001), 9-hole peg test (r = -0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) (r = -0.27, p < 0.001). UCCbrain, a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.