Predicting Intervention Responsiveness to Improve Rehabilitation in People with Multiple Sclerosis

Principal Investigator: Kathleen Zackowski

Sponsored by the National Multiple Sclerosis Society -- RG 4668-A-1.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) distinguished pathologically by inflammatory demyelination and axonal injury. It is characterized by a progressive functional decline although the course and clinical manifestations of the disease vary considerably from one patient to another, depending in part on the location of plaques (e.g., motor or sensory tracts within the CNS). The presently available pharmacologic treatments offer protection from new attacks, but do not help with recovery; thus in many cases patients rely only on rehabilitation for improvement. Because MS is so heterogeneous, the details of how and why individuals are responsive (or not responsive) to rehabilitative interventions may be critical for identifying characteristics that are treatable.

Here we propose to determine whether measures of clinical impairments and tract specific MRI can improve our ability to predict who will be most responsive to a progressive resistance exercise intervention and improve functional movement. We will perform a 12-week progressive resistive training intervention. We will measure sensory and motor impairments, walking ability, and other functional tasks before and after the intervention. We will also use diffusion tensor imaging (DTI), an advanced tract specific MRI technique that quantifies axonal loss and demyelination. DTI will be done before treatment to assess the integrity of two of the major motor (Corticospinal, CST) and sensory (Dorsal column-medial lemniscus, DC-ML) tracts across the full extent of the cervical spinal cord and brain.

We hypothesize that a combination of impairment measures and MRI-based measures will predict improvement in functional movements following three months of progressive resistance training. To test these hypotheses, we are using a rigorous biologic approach that combines clinical evaluation, advanced neuroimaging methods, and measures of impairment and disability to provide a more precise prognosis in terms of physical disability and to predict who is likely to respond to a physical intervention. We think that studying the neurobiology of myelin and axon integrity in combination with clinical and impairment measures will lead to both theoretical insights for improving rehabilitation for individuals with MS and to novel treatment strategies based on biological rather than empirical principles.