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Abstract
Objective To characterize the distribution and regional evolution of cervical cord atrophy in patients with multiple sclerosis (MS) in a multicenter dataset.
Methods MRI and clinical evaluations were acquired from 179 controls and 435 patients (35 clinically isolated syndromes [CIS], 259 relapsing-remitting multiple sclerosis [RRMS], 99 secondary progressive multiple sclerosis [SPMS], and 42 primary progressive multiple sclerosis [PPMS]). Sixty-nine controls and 178 patients underwent a 1-year MRI and clinical follow-up. Patients were classified as clinically stable/worsened according to their disability change. Longitudinal changes of cord atrophy were investigated with linear mixed-effect models. Sample size calculations were performed using age-, sex- and site-adjusted annualized percentage normalized cord cross-sectional area (CSAn) changes.
Results Baseline CSAn was lower in patients with MS vs controls (p < 0.001), but not different between controls and patients with CIS or between patients with early RRMS (disease duration ≤5 years) and patients with CIS. Patients with late RRMS (disease duration >5 years) showed significant cord atrophy vs patients with early RRMS (p = 0.02). Patients with progressive MS had decreased CSAn (p < 0.001) vs patients with RRMS. Atrophy was located between C1/C2 and C5 in patients with RRMS vs patients with CIS, and widespread along the cord in patients with progressive MS vs patients with RRMS, with an additional C5/C6 involvement in patients with SPMS vs patients with PPMS. At follow-up, CSAn decreased in all phenotypes (p < 0.001), except CIS. Cord atrophy rates were highest in patients with early RRMS and clinically worsened patients, who had a more widespread cord involvement than stable patients. The sample size per arm required to detect a 50% treatment effect was 118 for patients with early RRMS.
Conclusions Cord atrophy increased in MS during 1 year, except for CIS. Faster atrophy contributed to explain clinical worsening.
Glossary
- AS=
- active surface;
- CIS=
- clinically isolated syndrome;
- CSA=
- cross-sectional area;
- CSAn=
- normalized cross-sectional area;
- DE=
- dual echo;
- DMT=
- disease-modifying treatments;
- EDSS=
- Expanded Disability Status Scale;
- FLAIR=
- fluid-attenuated inversion recovery;
- FSE=
- fast spin-echo;
- GM=
- gray matter;
- HC=
- healthy controls;
- ICC=
- intraclass correlation coefficient;
- LV=
- lesion volumes;
- MS=
- multiple sclerosis;
- NBV=
- normalized brain volume;
- NWMV=
- normalized white matter volume;
- PBVC=
- percentage brain volume change;
- PPMS=
- primary progressive multiple sclerosis;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis;
- STIR=
- short-tau inversion recovery
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed in the appendix 2 at the end of the article.
- Received November 7, 2018.
- Accepted in final form June 4, 2019.
- © 2019 American Academy of Neurology
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