Brain Advance Access published online on March 18, 2009
Brain, doi:10.1093/brain/awp032
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Sensorimotor dysfunction in multiple sclerosis and column-specific magnetization transfer-imaging abnormalities in the spinal cord
1 Department of Physical Medicine and Rehabilitation, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA 2 Department of Neurology, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA 3 Motion Analysis Laboratory, Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205, USA 4 Department of Radiology, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA 5 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway, Baltimore, MD 21205, USA 6 Department of Neuroscience, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA
Correspondence to:
Kathleen M. Zackowski, PhD, Motion Analysis Laboratory, Kennedy Krieger Institute, Johns Hopkins University, 707 N. Broadway, Baltimore, MD 21205, USA E-mail: zackowski{at}kennedykrieger.org
The human spinal cord contains segregated sensory and motor pathways that have been difficult to quantify using conventional magnetic resonance imaging (MRI) techniques. Multiple sclerosis is characterized by both focal and spatially diffuse spinal cord lesions with heterogeneous pathologies that have limited attempts at linking MRI and behaviour. We used a novel magnetization-transfer-weighted imaging approach to quantify damage to spinal white matter columns and tested its association with sensorimotor impairment. We studied 42 participants with multiple sclerosis who each underwent MRI at 3 Tesla and quantitative tests of sensorimotor function. We measured cerebrospinal-fluid-normalized magnetization-transfer signals in the dorsal and lateral columns and grey matter of the cervical cord. We also measured brain lesion volume, cervical spinal cord lesion number and cross-sectional area, vibration sensation, strength, walking velocity and standing balance. We used linear regression to assess the relationship between sensorimotor impairment and MRI abnormalities. We found that the dorsal column cerebrospinal-fluid-normalized magnetization-transfer signal specifically correlated with vibration sensation (R = 0.58, P < 0.001) and the lateral column signal with strength (R = –0.45, P = 0.003). Spinal cord signal measures also correlated with walking and balance dysfunction. A stepwise multiple regression showed that the dorsal column signal and diagnosis subtype alone explained a significant portion of the variance in sensation (R2 = 0.54, P < 0.001), whereas the lateral column signal and diagnosis subtype explained a significant portion of the variance in strength (R2 = 0.30, P < 0.001). These results help to understand the anatomic basis of sensorimotor disability in multiple sclerosis and have implications for testing the effects of neuroprotective and reparative interventions.
Key Words: strength; sensation; corticospinal tract; dorsal column medial lemniscal tract; magnetic resonance imaging
Abbreviations: EDSS, expanded disability status scale; FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging; MT, magnetization transfer; MTCSF, cerebrospinal-fluid-normalized magnetization-transfer
Received October 28, 2008. Revised January 22, 2009. Accepted January 26, 2009.