With increasing rates of survival throughout the past several years, stroke remains one of the leading causes of adult disability. Following the onset of stroke, spontaneous mechanisms of recovery at the cellular, molecular, and systems levels ensue. The degree of spontaneous recovery is generally incomplete and variable among individuals. Typically, the best recovery outcomes entail the restitution of function in injured but surviving neural matter. An assortment of restorative therapies exists or is under development with the goal of potentiating restitution of function in damaged areas or in nearby ipsilesional regions by fostering neuroplastic changes, which often rely on mechanisms similar to those observed during spontaneous recovery. Advancements in stroke rehabilitation depend on the elucidation of both spontaneous and therapeutic-driven mechanisms of recovery. Further, the implementation of neural biomarkers in research and clinical settings will enable a multimodal approach to probing brain state and predicting the extent of post-stroke functional recovery. This review will discuss spontaneous and therapeutic-induced mechanisms driving post-stroke functional recovery while underscoring several potential restorative therapies and biomarkers.

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Spontaneous and Therapeutic-Induced Mechanisms of Functional Recovery After Stroke

Purpose of reviewPrescribing 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 neurorehabilitati

Dose and timing in neurorehabilitation: prescribing motor therapy after stroke.

Background
In people who have had a stroke, upper limb paresis affects many activities of daily life. Reducing disability is therefore a major aim of rehabilitative interventions. Despite preserving or recovering movement ability after stroke, sometimes people do not fully realise this ability in their everyday activities. Constraint-induced movement therapy (CIMT) is an approach to stroke rehabilitation that involves the forced use and massed practice of the affected arm by restraining the unaffected arm. This has been proposed as a useful tool for recovering abilities in everyday activities.

Objectives
To assess the efficacy of CIMT, modified CIMT (mCIMT), or forced use (FU) for arm management in people with hemiparesis after stroke.

Search methods
We searched the Cochrane Stroke Group trials register (last searched June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library Issue 1, 2015), MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (1982 to January 2015), and the Physiotherapy Evidence Database (PEDro; January 2015).

Selection criteria
Randomised control trials (RCTs) and quasi-RCTs comparing CIMT, mCIMT or FU with other rehabilitative techniques, or none.

Data collection and analysis
One author identified trials from the results of the electronic searches according to the inclusion and exclusion criteria, three review authors independently assessed methodological quality and risk of bias, and extracted data. The primary outcome was disability.

Main results
We included 42 studies involving 1453 participants. The trials included participants who had some residual motor power of the paretic arm, the potential for further motor recovery and with limited pain or spasticity, but tended to use the limb little, if at all. The majority of studies were underpowered (median number of included participants was 29) and we cannot rule out small-trial bias. Eleven trials (344 participants) assessed disability immediately after the intervention, indicating a non-significant standard mean difference (SMD) 0.24 (95% confidence interval (CI) -0.05 to 0.52) favouring CIMT compared with conventional treatment. For the most frequently reported outcome, arm motor function (28 studies involving 858 participants), the SMD was 0.34 (95% CI 0.12 to 0.55) showing a significant effect (P value 0.004) in favour of CIMT. Three studies involving 125 participants explored disability after a few months of follow-up and found no significant difference, SMD -0.20 (95% CI -0.57 to 0.16) in favour of conventional treatment.

Authors' conclusions
CIMT is a multi-faceted intervention where restriction of the less affected limb is accompanied by increased exercise tailored to the person’s capacity. We found that CIMT was associated with limited improvements in motor impairment and motor function, but that these benefits did not convincingly reduce disability. This differs from the result of our previous meta-analysis where there was a suggestion that CIMT might be superior to traditional rehabilitation. Information about the long-term effects of CIMT is scarce. Further trials studying the relationship between participant characteristics and improved outcomes are required.

Constraint‐induced movement therapy for upper extremities in people with stroke

TMS measures of motor cortex function after stroke: A meta-analysis

Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP.

https://journals.sagepub.com/doi/pdf/10.1177/1545968315625838

Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy.

OBJECTIVE
Constraint-induced movement therapy (CIMT) leads to improvement in upper extremity movement and cortical reorganization after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke).

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Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study.

Yusif Mohammad

Papers

Differential patterns of cortical reorganization following constraint-induced movement therapy during early and late period after stroke: A preliminary study.