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

Burcu Zeydan; Jiye Son; Nur Neyal; Christopher G Schwarz; Elizabeth J Atkinson; Holly A Morrison; Nabeela Nathoo; Kejal Kantarci; Eoin P Flanagan; John D Port; Orhun H Kantarci

doi:10.1177/13524585241311441

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

Mult Scler. 2025 Jan 18:13524585241311441. doi: 10.1177/13524585241311441. Online ahead of print.

Authors

Burcu Zeydan^{1

2

3}, Jiye Son¹, Nur Neyal¹, Christopher G Schwarz¹, Elizabeth J Atkinson⁴, Holly A Morrison², Nabeela Nathoo⁵, Kejal Kantarci¹, Eoin P Flanagan^{2

6}, John D Port^{1

2}, Orhun H Kantarci^{2

6}

Affiliations

¹ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
² Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
³ Women's Health Research Center, Mayo Clinic, Rochester, MN, USA.
⁴ Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
⁵ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
⁶ Department of Neurology, Mayo Clinic, Rochester, MN, USA.

PMID: 39825669
DOI: 10.1177/13524585241311441

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.

Keywords: Multiple sclerosis; age; menopause; progression; sex; upper cervical spinal cord.