The Specific Requirements of Neural Repair Trials for Stroke

Abstract

Novel molecular, cellular and pharmacological therapies to stimulate repair of sensorimotor circuits after stroke are entering clinical trials. Compared to acute neuroprotection and thrombolysis studies, clinical trials for repair in subacute and chronic hemiplegic participants have a different time course for delivery of an intervention, different mechanisms of action within the milieu of the injury, distinct relationships to the amount of physical activity and skills practice of participants, and need to include more refined outcome measures. This review examines the biological interaction of targeted rehabilitation with neural repair strategies to optimize outcomes. We suggest practical guidelines for the incorporation of inexpensive skills training and exercise at home. In addition, we describe some novel outcome measurement tools, including wearable sensors, to obtain the more detailed outcomes that may identify at least some minimal level of success from cellular and regeneration interventions. Thus, proceeding in the shadow of acute stroke trial designs may unnecessarily limit the mechanisms of action of new repair strategies, reduce their impact on participants, and risk missing important behavioral outcomes.

Agreed Definitions and a Shared Vision for New Standards in Stroke Recovery Research: The Stroke Recovery and Rehabilitation Roundtable Taskforce

“…6,29 These terms are often used in recovery research without adequate definition. Building on previous work by Dobkin and Carmichael, 28 we developed the framework shown in Figure 1. The framework is strongly informed by pre-clinical research in animal models of stroke, [30][31][32][33] as well as individuals with stroke, 18,27,34 particularly from studies of the motor system.…”

Behavioral self-management strategies for practice and exercise should be included in neurologic rehabilitation trials and care

“…1,2,3 Aerobic and resistance exercise also induce neuroplasticity by modulation of similar molecular, cellular, synaptic and genetic adaptations. Thus, efforts to increase walking and affected upper extremity practice, as well as exercise for fitness and strengthening during and beyond the time of formal rehabilitation have a compelling theoretical basis.…”

A Rehabilitation-Internet-of-Things in the Home to Augment Motor Skills and Exercise Training

“…35 Perhaps the motor learning theory works best within the most intrinsically adaptive period after stroke, the first three months. 36 Motor gains for selective arm and leg movements, particularly what is measured by the Fugl-Meyer Motor Assessment, tend to reach a so-called proportional recovery plateau in the first few months after stroke, 37,38 with adaptive strategies increasingly incorporated over time when trying to accomplish any given task. Thus, efforts are needed to provide as much rehabilitation as feasible immediately after discharge from inpatient care, because this period may be critical to the maximum success of a fully scaled mantra training strategy.…”