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Abstract
Objective: To find the strongest neuroimaging predictors for motor dysfunction using conventional and quantitative imaging measures focusing on the corticospinal tract (CST) in a large cohort of patients with long-standing multiple sclerosis (MS).
Methods: In this cross-sectional study, a wide spectrum of neuroimaging measures at the whole-brain, cervical, and CST level were analyzed in 195 patients with MS and 54 healthy controls. Motor function was assessed using the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test, Timed 25-Foot Walk Test, and Multiple Sclerosis Walking Scale. Associations between damage in different parts of the motor system and motor functioning were assessed using stepwise linear regression.
Results: Patients had an average disease duration of 19.98 (±6.99) years and a median EDSS score of 4 (range: 1.0–8.0). EDSS score was associated with number of infratentorial and cervical cord lesions, lesion volume in the CST, and mean upper cervical cord area (adjusted R2 = 0.403). Timed 25-Foot Walk Test score was associated with number of infratentorial lesions and cerebellar volume (adjusted R2 = 0.150), 9-Hole Peg Test score with number of infratentorial lesions and thickness of the cortex connected to the CST (adjusted R2 = 0.245), and Multiple Sclerosis Walking Scale with number of infratentorial and cervical lesions, thickness of the cortex connected to the CST, and mean upper cervical cord area (adjusted R2 = 0.354).
Conclusions: Motor dysfunction in MS has a complex substrate that cannot be ascribed to a single neuroimaging finding, but is the consequence of infratentorial and spinal cord damage, as well as damage in the CST.
GLOSSARY
- AD=
- axial diffusivity;
- CST=
- corticospinal tract;
- CTCST=
- cortical thickness of cortical area connected to corticospinal tract;
- DIR=
- double inversion recovery;
- DTI=
- diffusion tensor imaging;
- EDSS=
- Expanded Disability Status Scale;
- FA=
- fractional anisotropy;
- FLAIR=
- fluid-attenuated inversion recovery;
- FSL=
- FMRIB's Software Library;
- IFS=
- infratentorial functional system;
- JHU=
- Johns Hopkins University;
- MD=
- mean diffusivity;
- MS=
- multiple sclerosis;
- MSWS=
- Multiple Sclerosis Walking Scale;
- MUCCA=
- mean upper cervical cord area;
- NAWM=
- normal-appearing white matter;
- NBLV=
- normalized brain lesion volume;
- NBV=
- normalized brain volume;
- 9-HPT=
- 9-Hole Peg Test;
- NLVCST=
- normalized corticospinal tract lesion volume;
- PFS=
- pyramidal functional system;
- PPMS=
- primary progressive multiple sclerosis;
- RD=
- radial diffusivity;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis;
- TWT=
- Timed 25-Foot Walk Test;
- WM=
- white matter
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Supplemental data at Neurology.org
- Received October 14, 2014.
- Accepted in final form March 24, 2015.
- © 2015 American Academy of Neurology
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