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Abstract
Objectives Gay matter (GM) involvement is clinically relevant in multiple sclerosis (MS). Using source-based morphometry (SBM), we characterized GM atrophy and its 1-year evolution across different MS phenotypes.
Methods Clinical and MRI data were obtained at 8 European sites from 170 healthy controls (HCs) and 398 patients with MS (34 with clinically isolated syndrome [CIS], 226 with relapsing-remitting MS [RRMS], 95 with secondary progressive MS [SPMS], and 43 with primary progressive MS [PPMS]). Fifty-seven HCs and 144 with MS underwent 1-year follow-up. Baseline GM loss, atrophy progression, and correlations with disability and 1-year clinical worsening were assessed.
Results SBM identified 26 cerebellar, subcortical, sensory, motor, and cognitive GM components. GM atrophy was found in patients with MS vs HCs in almost all components (p range <0.001–0.04). Compared to HCs, patients with CIS showed circumscribed subcortical, cerebellar, temporal, and salience GM atrophy, while patients with RRMS exhibited widespread GM atrophy. Cerebellar, subcortical, sensorimotor, salience, and frontoparietal GM atrophy was found in patients with PPMS vs HCs and in patients with SPMS vs those with RRMS. At 1 year, 21 (15%) patients had clinically worsened. GM atrophy progressed in MS in subcortical, cerebellar, sensorimotor, and fronto-temporo-parietal components. Baseline higher disability was associated (R2 = 0.65) with baseline lower normalized brain volume (β = −0.13, p = 0.001), greater sensorimotor GM atrophy (β = −0.12, p = 0.002), and longer disease duration (β = 0.09, p = 0.04). Baseline normalized GM volume (odds ratio 0.98, p = 0.008) and cerebellar GM atrophy (odds ratio 0.40, p = 0.01) independently predicted clinical worsening (area under the curve 0.83).
Conclusion GM atrophy differed across disease phenotypes and progressed at 1 year in MS. In addition to global atrophy measures, sensorimotor and cerebellar GM atrophy explained baseline disability and clinical worsening.
Glossary
- CI=
- confidence interval;
- CIS=
- clinically isolated syndrome;
- DMN=
- default mode network;
- DMT=
- disease-modifying treatment;
- EDSS=
- Expanded Disability Status Scale;
- FA=
- flip angle;
- GM=
- gray matter;
- HC=
- healthy control;
- IC=
- independent component;
- ICA=
- IC analysis;
- LV=
- lesion volume;
- MAGNIMS=
- Magnetic Resonance Imaging in Multiple Sclerosis;
- MS=
- multiple sclerosis;
- NBV=
- normalized brain volume;
- NGMV=
- normalized GM volume;
- NWMV=
- normalized WM volume;
- OR=
- odds ratio;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing-remitting MS;
- SBM=
- source-based morphometry;
- SPMS=
- secondary progressive MS;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- WM=
- white matter
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.
The link for the list of MAGNIMS Study Group coinvestigators is provided in the appendix 2 at the end of the article.
- Received April 29, 2020.
- Accepted in final form December 3, 2020.
- © 2021 American Academy of Neurology
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