Cervical and thoracic cord atrophy in multiple sclerosis phenotypes: Quantification and correlation with clinical disability

Yair Mina; Shila Azodi; Tsemacha Dubuche; Frances Andrada; Ikesinachi Osuorah; Joan Ohayon; Irene Cortese; Tianxia Wu; Kory R Johnson; Daniel S Reich; Govind Nair; Steven Jacobson

doi:10.1016/j.nicl.2021.102680

Cervical and thoracic cord atrophy in multiple sclerosis phenotypes: Quantification and correlation with clinical disability

Neuroimage Clin. 2021:30:102680. doi: 10.1016/j.nicl.2021.102680. Epub 2021 Apr 28.

Authors

Yair Mina¹, Shila Azodi², Tsemacha Dubuche³, Frances Andrada⁴, Ikesinachi Osuorah⁴, Joan Ohayon⁴, Irene Cortese⁴, Tianxia Wu⁵, Kory R Johnson⁶, Daniel S Reich⁷, Govind Nair⁸, Steven Jacobson⁹

Affiliations

¹ Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
² Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Neuroimmunology Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
³ Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁴ Neuroimmunology Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁵ Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁶ Bioinformatics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁷ Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁸ Neuroimmunology Clinic, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States; Quantitative MRI Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
⁹ Viral Immunology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States. Electronic address: jacobsons@nih.gov.

Abstract

Objective: We sought to characterize spinal cord atrophy along the entire spinal cord in the major multiple sclerosis (MS) phenotypes, and evaluate its correlation with clinical disability.

Methods: Axial T₁-weighted images were automatically reformatted at each point along the cord. Spinal cord cross-sectional area (SCCSA) were calculated from C1-T10 vertebral body levels and profile plots were compared across phenotypes. Average values from C2-3, C4-5, and T4-9 regions were compared across phenotypes and correlated with clinical scores, and then categorized as atrophic/normal based on z-scores derived from controls, to compare clinical scores between subgroups. In a subset of relapsing-remitting cases with longitudinal scans these regions were compared to change in clinical scores.

Results: The cross-sectional study consisted of 149 adults diagnosed with relapsing-remitting MS (RRMS), 49 with secondary-progressive MS (SPMS), 58 with primary-progressive MS (PPMS) and 48 controls. The longitudinal study included 78 RRMS cases. Compared to controls, all MS groups had smaller average regions except RRMS in T4-9 region. In all MS groups, SCCSA from all regions, particularly the cervical cord, correlated with most clinical measures. In the RRMS cohort, 22% of cases had at least one atrophic region, whereas in progressive MS the rate was almost 70%. Longitudinal analysis showed correlation between clinical disability and cervical cord thinning.

Conclusions: Spinal cord atrophy was prevalent across MS phenotypes, with regional measures from the RRMS cohort and the progressive cohort, including SPMS and PPMS, being correlated with disability. Longitudinal changes in the spinal cord were documented in RRMS cases, making it a potential marker for disease progression. While cervical SCCSA correlated with most disability and progression measures, inclusion of thoracic measurements improved this correlation and allowed for better subgrouping of spinal cord phenotypes. Cord atrophy is an important and easily obtainable imaging marker of clinical and sub-clinical progression in all MS phenotypes, and such measures can play a key role in patient selection for clinical trials.

Keywords: MRI; Multiple Sclerosis; Spine.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adult
Atrophy / pathology
Cervical Cord* / diagnostic imaging
Cervical Cord* / pathology
Cross-Sectional Studies
Disability Evaluation
Disease Progression
Humans
Longitudinal Studies
Magnetic Resonance Imaging
Multiple Sclerosis* / diagnostic imaging
Multiple Sclerosis* / pathology
Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting* / pathology
Phenotype
Spinal Cord / pathology