title: Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis.
abstract: At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology. Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0-6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging. Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p < 0.04) and magnetization transfer ratio (r > 0.29; p < 0.03) measures. Although the Expanded Disability Status Scale was highly correlated with walking measures, it was not significantly related to either corticospinal tract fractional anisotropy or magnetization transfer ratio (p > 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information. Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.
authors.affiliation: Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD, USA; Johns Hopkins School of Medicine, Department of Physical Medicine and Rehabilitation, Baltimore, MD, USA; Wayne State University, Program in Physical Therapy, Department of Neurology, Detroit, MI, USA.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Fritz
authors.affiliation: Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keller
authors.affiliation: Johns Hopkins School of Medicine, Department of Neurology, Baltimore, MD, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.affiliation: Motion Analysis Laboratory, Kennedy Krieger Institute, Baltimore, MD, USA; Johns Hopkins School of Medicine, Department of Physical Medicine and Rehabilitation, Baltimore, MD, USA; Johns Hopkins School of Medicine, Department of Neurology, Baltimore, MD, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Zackowski
mesh_terms: D000328:Adult; D016880:Anisotropy; D016022:Case-Control Studies; D038524:Diffusion Magnetic Resonance Imaging; D004185:Disability Evaluation; D005260:Female; D020233:Gait Disorders, Neurologic / Q000175:diagnosis* / Q000209:etiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology*; D053580:Muscle Strength / Q000502:physiology; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging*; D016138:Walking / Q000502:physiology*
keywords: Diffusion tensor imaging; Magnetization transfer imaging; Multiple sclerosis; Strength; Walking