Role of Alternate Sensorimotor Pathway Degeneration in Motor Function in Acute Stroke

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Stroke is a growing cardiovascular concern in the United States, with approximately 7 million individuals reporting a stroke event. Stroke is a particular concern in the South Texas Rio Grande Valley, where incidence is approximately 3.8% (compared to 0.27% in the general population). Common limitations after a stroke include: gait instability, upper limb paralysis, sensory deficits, pain, depression and cognitive impairments. Of all impairments, paresis of the upper and lower limb remains the most common. Rehabilitation strategies can improve upper and lower limb mobility in stroke survivors. Unfortunately, though, the majority of rehabilitation strategies employ a ‘one-size-fits-all’ approach, thereby limiting efficacy in the heterogenous stroke population. To address this limitation, the use of biomarkers has emerged as a means to inform patient selection for the differing rehabilitation approaches. In general, biomarkers have focused on how changes in corticospinal tract structure or function influence recovery. Overall, published work has suggested that changes to the corticospinal tract pathways in the brain may influence functional recovery in patients with stroke. However, current rehabilitation approaches targeting spared corticospinal pathways have had limited efficacy in patient populations, particularly those with severe impairments. Therefore, it is vital to understand what other pathways beyond the corticospinal tract may influence functional recovery as to better inform clinical treatment of patients with stroke. Here, we propose to evaluate the progression of alternate sensorimotor pathway degeneration in patients with stroke by imaging the brainstem and spinal cord, where the sensorimotor pathways diverge. To evaluate our premise, we will perform a longitudinal, repeated-measures clinical study in 30 subjects with acute ischemic stroke. We will evaluate sensorimotor pathway neurodegeneration in the cervical, thoracic and lumbar spinal cord and in the brainstem by collecting magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) at two-, twelve- and twenty-four weeks post-stroke. Neuroimaging will also be collected in 10 age-matched healthy controls. Our aims will: (1) evaluate alternate sensorimotor pathway neurodegeneration in the brain stem and (2) spinal cord and (3) determine how neurodegeneration affects motor function and impairment in acute stroke patients. Our central hypothesis is that degeneration of the alternate sensorimotor pathways is progressive after a first-time stroke and will affect both the lesioned and non-lesioned hemisphere pathways to significantly impact motor function. The results from our study will provide the basis for larger-scale clinical trials evaluating alternate sensorimotor pathway degeneration. Further, our work will provide the framework for whether treatment options targeting alternate sensorimotor pathways should be considered in populations with acute stroke.