Dose and timing in neurorehabilitation

Abstract

Purpose of the review Prescribing the most appropriate dose of motor therapy for individual patients is a challenge because minimal data are available and a large number of factors are unknown. This review explores the concept of dose and reviews the most recent findings in the field of neurorehabilitation, with a focus on relearning motor skills post stroke. Recent findings Appropriate dosing involves the prescription of a specific amount of an active ingredient, at a specific frequency and duration. Dosing parameters, particularly amount, are not well-defined or quantified in most studies. Compiling data across studies indicates a positive, moderate dose-response relationship, indicating that more movement practice results in better outcomes. This relationship is confounded by time post stroke however, where longer durations of scheduled therapy may not be beneficial in the first few hours, days, and/or weeks. Summary These findings suggest that substantially more movement practice may be necessary to achieve better outcomes for people living with the disabling consequences of stroke. Preclinical investigations are needed to elucidate many of the unknowns and allow for a more biologically-driven rehabilitation prescription process. Likewise, clinical investigations are needed to determine the dose-response relationships and examine the potential dose-timing interaction in humans.

Critique of Home Constraint-Induced Movement Therapy Trial

“…However, the authors did not comment on the lower than intended dosage or explicitly consider how this may have impacted their findings. Given our emerging understanding of the relation between dose of therapy and functional gains, 8,9 this may be a key limitation of the present work. The venue for therapy was at home for Home CIMT but the authors do not state whether the majority of sessions took place in a clinic setting for the standard care group.…”

A rule-based, dose-finding design for use in stroke rehabilitation research: methodological development

“…Recommendations for higher doses of physiotherapy in stroke rehabilitation, based on findings from meta-analyses [1], are questioned by findings that higher doses may not always produce better recovery [2][3][4][5]. This could be because clinical recommendations based on metaanalyses of dose [6] may be insufficiently nuanced in respect of potential influential factors on dose response.…”

Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury

“…Human and animal studies suggest that motor rehabilitative practice can improve motor function and drive brain remodeling following stroke (Dimyan and Cohen, 2011; Dobkin, 2004; Johansson, 2000; Jones and Adkins, 2010, 2015; Lang et al, 2015). Motor “relearning” and task-specific practice are considered essential in driving this neural plasticity (Johansson, 2000; Jones and Adkins, 2010; Kleim and Jones, 2008; Lang et al, 2015).…”

“…Motor “relearning” and task-specific practice are considered essential in driving this neural plasticity (Johansson, 2000; Jones and Adkins, 2010; Kleim and Jones, 2008; Lang et al, 2015). Following an experimental stroke, animals that repeatedly practice with their impaired limb on a reach-to-grasp task, a skilled learning task, demonstrate enhanced forelimb motor recovery compared to non-trained controls (Castro-Alamancos and Borrel, 1995; Maldonado et al, 2008; Nudo et al, 1996; Tennant et al, 2014).…”

“…In squirrel monkeys, rats and mice impaired forelimb reaching practice has also been shown to spare motor cortical tissue around the lesion and prevent the loss of movement representation in the remaining motor cortex, measured with intracortical microstimulation mapping (Nudo et al, 1996) and results in enlarged forelimb motor representative maps compared to untrained controls (Conner et al, 2005; Tennant et al, 2014). Clinically, several studies also indicate that the more a movement is practiced the better people recover function; however, the duration and intensity of therapy may need to be titrated depending on time after stroke (Lang et al, 2015). …”