Cervical Spinal Cord Atrophy in Multiple Sclerosis: Age, Sex, and Hormonal Status
Nur Neyal1, jiye son1, Christopher Schwarz1, Elizabeth Atkinson2, Holly Morrison3, Nabeela Nathoo5, Kejal Kantarci1, Eoin Flanagan4, John Port1, Orhun Kantarci4, Burcu Zeydan1
1Radiology, 2Quantitative Sciences, 3Center for Multiple Sclerosis and Autoimmune Neurology, 4Neurology, Mayo Clinic, 5Neurology, University of Alberta
Objective:
Investigate the influence of age, sex, and menopause on upper cervical spinal cord (UCC) atrophy and its association with disability metrics in persons with multiple sclerosis (pwMS)
Background:
Men with MS often experience a more aggressive disease course earlier in life, whereas women demonstrate accelerated disability worsening after menopause. In parallel, men show a more prominent brain atrophy early on, while brain atrophy rates become similar between sexes after 50 years of age. However, sex and hormonal differences in spinal cord (SC) atrophy are understudied in MS.
Design/Methods:
UCC area was obtained from 3T brain MRIs using an established automated method in pwMS and controls. Clinical measures, including expanded disability status scale (EDSS) and MS Functional Composite (MSFC), were obtained in pwMS.
Results:
When controls (n=118) were age- and sex-matched to pwMS (n=118), pwMS (51.4±5.3 mm2) had a smaller UCC area than controls (54.2±4.4 mm2, p<0.001). UCC area inversely correlated with age in pwMS (r=–0.24, p=0.010) but not in controls (r=–0.03, p=0.786). In the entire pwMS cohort (n=173; 413 MRIs), UCC was smaller in; 1) men (49.5±5.9 mm2) than women (51.6±5.5 mm2, p<0.001), 2) postmenopausal (49.4±5.6 mm2) than premenopausal women (52.9±4.1 mm2, p<0.001), and 3) progressive (47.5±5.6 mm2) than relapsing MS (52.1±5.2 mm2, p<0.001). Using the mean age at menopause (47.0±5.9 years), men were classified as younger men (18–47 years) and older men (>47 years). Consequently, UCC was smaller in younger men (50.3±6.7 mm²) compared with premenopausal women (52.9±4.1 mm², p=0.001), but similar between older men (48.5±4.4 mm²) and postmenopausal women (49.4±5.6 mm², p=0.318). Smaller UCC also correlated with longer disease duration (r=-0.39, p<0.001), worse 9-hole peg test scores (r=-0.26, p=0.005), and higher frequency of EDSS≥6 (r=-0.27, p<0.001).
Conclusions:
Older age, male sex, and menopause correlate with greater SC atrophy, which is an important biomarker of progressive MS and disability in MS.
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