I-Score: Intensive Stroke Cycling for Optimal Recovery and Economic Value

Overview

Traditional rehabilitation approaches are time and personnel intensive and costly, and leave \~75% of stroke survivors with residual disability. We propose a clinical trial to determine effects of forced aerobic exercise (FE; i.e., mechanically supplemented) in facilitating upper and lower extremity motor recovery post-stroke in an outpatient rehabilitation setting, to elucidate neural and biochemical substrates of FE-induced motor recovery, and to evaluate cost effectiveness of a FE-centered intervention compared to traditional stroke rehabilitation. The global effect of FE has the potential to enhance recovery in a growing population of stroke survivors in a cost-effective manner, thus accelerating its clinical acceptance.

Traditional rehabilitation approaches following stroke involve 1:1 motor learning-based training to facilitate recovery of upper extremity (UE) and lower extremity (LE) function. These time- and personnel-intensive approaches are costly, yet leave \~75% of stroke survivors with residual disability. More effective alternative approaches to facilitate motor recovery following stroke have not been adopted clinically due to excessive time and cost. To advance clinical care, both effectiveness and cost of a candidate intervention must be considered simultaneously. Aerobic exercise (AE) is known to improve cardiovascular function following stroke and central nervous system (CNS) function in older adults and neurological populations. Strong theoretical arguments suggest that AE may facilitate motor recovery following stroke. A protocol that rigorously tests this theory in the subacute stroke population is warranted. Animal studies, coupled with our preliminary data, indicate a specific type of exercise - forced aerobic exercise (FE), where volitional movements are mechanically supplemented - improves motor recovery following stroke. The mechanical assistance provided by FE enables patients to achieve a more rapid and consistent exercise pattern beyond their volitional capabilities while maintaining their aerobic effort within a beneficial range. In our initial studies, persons completing FE cycling followed by a reduced dose of UE motor task practice exhibited greater recovery of UE motor function compared to those completing unassisted AE and motor task practice or extended sessions of motor task practice alone. Animal studies have shown that FE triggers the release of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), thought to be critical building blocks for neuroplasticity. Project Hypothesis: FE facilitates high-intensity AE, which triggers growth factors essential for neuroplasticity, thereby 'priming' the CNS to facilitate motor recovery associated with motor retraining therapies. We propose a prospective, pragmatic clinical trial to determine effects of FE in facilitating UE and LE motor recovery post-stroke in an outpatient rehabilitation setting, to elucidate neural and biochemical substrates of FE-induced motor recovery, and to evaluate cost effectiveness of a FE-centered intervention compared to traditional stroke rehabilitation. Aim 1: Determine effects of FE+rehab vs. time-matched rehab on the recovery of UE motor function. Aim 2: Determine effects of FE+rehab vs. time-matched rehab on recovery of lower extremity motor function. Aim 3: Determine effects of FE+rehab vs. rehab on electrophysiological and biochemical markers of neuroplasticity. Aim 4: Evaluate cost-effectiveness of FE+rehab vs. rehab. The global effect of FE has the potential to enhance recovery in a growing population of stroke survivors in a cost-effective manner, thus accelerating its clinical acceptance. Our mechanistic aim will elucidate the effects of each approach on substrates underlying neuroplasticity.