Sponsors: NIH NICHD, Dana Foundation, Montel Williams MS Foundation

Multiple sclerosis (MS) affects approximately 300,000 adults in the United States and up to 2 million worldwide 1. It is a chronic recurrent inflammatory disorder that typically results in injury to the myelin sheaths, the oligodendrocytes, the axons and the nerve cells themselves in both the brain and spinal cord 2,3. The CNS lesions that occur in multiple sclerosis can cause many clinical deficits, depending on their location and extent, often affecting locomotion to a great extent. Conventional magnetic resonance imaging techniques provide a means for diagnosing and identifying new lesions in individuals with MS. However, the correlation between conventional MRI and clinical symptoms of MS is poor, possibly because conventional imaging modalities do not produce a quantitative evaluation of tissue and are relatively insensitive to specific underlying pathology such as demyelination and axonal damage 4,5. Therefore, it may be valuable to use alternative imaging techniques, such as magnetization transfer (MT) and diffusion tensor imaging (DTI) to quantify the extent of demyelination and axonal damage (and recovery), and track white matter pathways in the brain and spinal cord. These studies will incorporate measures of MT and DTI for the evaluation of white matter integrity; in addition we will evaluate sensorimotor impairments of sensation, strength, spasticity, and ataxia, and relate these to locomotor function. These studies will test the general hypothesis that, in MS and following an acute exacerbation the pattern of white matter damage is predictive of locomotor recovery. These studies will investigate: 1) whether specific white matter tract abnormalities that occur following an acute exacerbation of MS correlate with specific sensorimotor impairments and features of their walking patterns, and 2) whether damage to specific white matter tracts (i.e., the corticospinal, dorsal column medial lemniscal and tracts to and from the cerebellum) can predict the recovery of locomotion after a relapse of MS. Results will, for the first time, provide important new insights into how sensorimotor impairments relate to mechanisms of locomotion as well as the role of white matter fiber tract changes during exacerbation and subsequent recovery of locomotion in people with MS. We think that studying the neurobiology of these changes (i.e., myelin and axon integrity) will lead to both theoretical insights into rehabilitation of individuals with MS and to novel treatment strategies based on biological rather than empirical principles.