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

Abstract

Background:

Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective:

Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Methods:

In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCC_brain) was obtained. Impact of sex and menopause on UCC_brain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated.

Results:

UCC_brain 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), UCC_brain 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). UCC_brain 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).

Conclusion:

UCC_brain, 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.