Effect of Exercise on Brain-Derived Neurotrophic Factor in Stroke Survivors: A Systematic Review and Meta-Analysis.

BACKGROUND: BDNF (brain-derived neurotrophic factor) is a biomarker of neuroplasticity linked with better functional outcomes after stroke. Early evidence suggests that increased concentrations after exercise may be possible for people with stroke, however it is unclear how exercise parameters influence BDNF concentration. METHODS: This systematic review and meta-analysis searched 7 electronic databases. Experimental or observational studies measuring changes in BDNF concentration after exercise in people poststroke were included. Data were extracted including characteristics of the study, participants, interventions, and outcomes. Several fixed and random effects meta-analyses were completed. RESULTS: Seventeen studies including a total of 687 participants met the eligibility criteria (6 randomized trials). Significant improvements were observed in BDNF concentration following a single session (mean difference, 2.49 ng/mL; [95% CI, 1.10-3.88]) and program of high intensity aerobic exercise (mean difference, 3.42 ng/mL; [95% CI, 1.92-4.92]). CONCLUSIONS: High intensity aerobic exercise can increase circulating BDNF concentrations, which may contribute to increased neuroplasticity. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42021251083.

Revisiting Poststroke Upper Limb Stratification: Resilience in a Larger Cohort.

BACKGROUND: Upper limb (UL) impairment in stroke survivors is both multifactorial and heterogeneous. Stratification of motor function helps identify the most sensitive and appropriate assessments, which in turn aids the design of effective and individualized rehabilitation strategies. We previously developed a stratification method combining the Grooved Pegboard Test (GPT) and Box and Block Test (BBT) to stratify poststroke UL motor function. OBJECTIVE: To investigate the resilience of the stratification method in a larger cohort and establish its appropriateness for clinical practice by investigating limitations of the GPT completion time. METHODS: Post hoc analysis of motor function for 96 community-dwelling participants with stroke (n = 68 male, 28 female, age 60.8 ± 14 years, 24.4 ± 36.6 months poststroke) was performed using the Wolf Motor Function Test (WMFT), Fugl-Meyer Assessment (F-M), BBT, and GPT. Hypothesis-free and hypothesis-based hierarchical cluster analyses were conducted to determine the resilience of the stratification method. RESULTS: The hypothesis-based analysis identified the same functional groupings as the hypothesis-free analysis: low (n = 32), moderate (n = 26), and high motor function (n = 38), with 3 exceptions. Thirty-three of the 38 participants with fine manual dexterity completed the GPT in ≤5 minutes. The remaining 5 participants took 6 to 25 minutes to place all 25 pegs but used alternative movement strategies to complete the test. The GPT time restriction changed the functional profile of the moderate and high motor function groups leading to more misclassifications. CONCLUSION: The stratification method unambiguously classifies participants by UL motor function. While the inclusion of a 5-minute cutoff time for the GPT is preferred for clinical practice, it is not recommended for stratification purposes.

Improved Kinematics and Motor Control in a Longitudinal Study of a Complex Therapy Movement in Chronic Stroke.

Impaired motor control post-stroke is typically measured using clinical assessments employing categorical and subjective scoring. We investigated quantitative kinematic parameters of a complex movement with therapy in chronic stroke. Tri-axial accelerometry of the more-affected arm of 24 patients was recorded during early- (day 2-3) and late- (days 12-14) therapy, and for 13 patients at 6-month follow-up. Clinical assessments included the classification of motor-function as low, moderate, or high. Kinematic parameters were measured during Wii-baseball swings to assess the effect of time and the level of motor-function. Clinical tests improved over time (all p < 0.01). Increased acceleration magnitude over time was significant only at proximal sensors (p < 0.05), and there was an effect of motor-function at distal sensors (p < 0.05). Normalized velocity decreased (p < 0.05) at all sensors over time. Peak acceleration and peak deceleration increased over time, predominately at proximal sensors. Kinematic parameters provide an objective and quantitative measure of change in motor-function that is not possible with clinical assessments. The complex patterns of change were not consistent between and within levels of motor-function but reflected improved motor control that was sustained over time. These data emphasize the potential for ongoing improvements in motor capacity in chronic stroke with additional rehabilitation.

The Role of Personalized Virtual Reality in Education for Patients Post Stroke-A Qualitative Case Series.

BACKGROUND: Education is essential to promote prevention of recurrent stroke and maximize rehabilitation; however, current techniques are limited and many patients remain dissatisfied. Virtual reality (VR) may provide an alternative way of conveying complex information through a more universal language. AIM: To develop and conduct preliminary assessments on the use of a guided and personalized 3D visualization education session via VR, for stroke survivors and primary caregivers. METHODS: Four poststroke patients and their 4 primary caregivers completed the 3D visualization education session as well as pre- and postintervention interviews. Each patient had a different stroke etiology (i.e., ischemic thrombotic stroke, ischemic embolic stroke, hemorrhagic stroke, and transient ischemic attack followed by ischemic stroke, respectively). This new approach uses preintervention interview responses, patient MRI and CT datasets, VR head mounted displays, 3D computer modeling, and game development software to develop the visualization. Pre- and postintervention interview responses were analyzed using a qualitative phenomenological methodology approach. RESULTS: All participants safely completed the study and were highly satisfied with the education session. In this subset of participants, prior formal stroke education provision was limited. All participants demonstrated varied improvements in knowledge areas including brain anatomy and physiology, brain damage and repair, and stroke-specific information such as individual stroke risk factors and acute treatment benefits. These improvements were accompanied by feelings of closure, acceptance, and a greater motivation to manage their stroke risk. CONCLUSIONS: Preliminary results suggest this approach provides a safe and promising educational tool to promote understanding of individualized stroke experiences.

Who teaches medical billing? A national cross-sectional survey of Australian medical education stakeholders.

IMPORTANCE: Billing errors and healthcare fraud have been described by the WHO as 'the last great unreduced health-care cost'. Estimates suggest that 7% of global health expenditure (US$487 billion) is wasted from this phenomenon. Irrespective of different payment models, challenges exist at the interface of medical billing and medical practice across the globe. Medical billing education has been cited as an effective preventative strategy, with targeted education saving $A250 million in Australia in 1 year from an estimated $A1-3 billion of waste. OBJECTIVE: This study attempts to systematically map all avenues of medical practitioner education on medical billing in Australia and explores the perceptions of medical education stakeholders on this topic. DESIGN: National cross-sectional survey between April 2014 and June 2015. No patient or public involvement. Data analysis-descriptive statistics via frequency distributions. PARTICIPANTS: All stakeholders who educate medical practitioners regarding clinical practice (n=66). 86% responded. RESULTS: There is little medical billing education occurring in Australia. The majority of stakeholders (70%, n=40) did not offer/have never offered a medical billing course. 89% thought medical billing should be taught, including 30% (n=17) who were already teaching it. There was no consensus on when medical billing education should occur. CONCLUSIONS: To our knowledge, this is the first attempt of any country to map the ways doctors learn the complex legal and administrative infrastructure in which they work. Consistent with US findings, Australian doctors may not have expected legal and administrative literacy. Rather than reliance on ad hoc training, development of an Australian medical billing curriculum should be encouraged to improve compliance, expedite judicial processes and reduce waste. In the absence of adequate education, disciplinary bodies in all countries must consider pleas of ignorance by doctors under investigation, where appropriate, for incorrect medical billing.

Rehabilitation and education are underutilized for mild stroke and TIA sufferers.

PURPOSE: Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. METHODS: Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. RESULTS: A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.

A Longitudinal Electromyography Study of Complex Movements in Poststroke Therapy. 2: Changes in Coordinated Muscle Activation.

Fine motor control is achieved through the coordinated activation of groups of muscles, or "muscle synergies." Muscle synergies change after stroke as a consequence of the motor deficit. We investigated the pattern and longitudinal changes in upper limb muscle synergies during therapy in a largely unconstrained movement in patients with a broad spectrum of poststroke residual voluntary motor capacity. Electromyography (EMG) was recorded using wireless telemetry from 6 muscles acting on the more-affected upper body in 24 stroke patients at early and late therapy during formal Wii-based Movement Therapy (WMT) sessions, and in a subset of 13 patients at 6-month follow-up. Patients were classified with low, moderate, or high motor-function. The Wii-baseball swing was analyzed using a non-negative matrix factorization (NMF) algorithm to extract muscle synergies from EMG recordings based on the temporal activation of each synergy and the contribution of each muscle to a synergy. Motor-function was clinically assessed immediately pre- and post-therapy and at 6-month follow-up using the Wolf Motor Function Test, upper limb motor Fugl-Meyer Assessment, and Motor Activity Log Quality of Movement scale. Clinical assessments and game performance demonstrated improved motor-function for all patients at post-therapy (p < 0.01), and these improvements were sustained at 6-month follow-up (p > 0.05). NMF analysis revealed fewer muscle synergies (mean ± SE) for patients with low motor-function (3.38 ± 0.2) than those with high motor-function (4.00 ± 0.3) at early therapy (p = 0.036) with an association trend between the number of synergies and the level of motor-function. By late therapy, there was no significant change between groups, although there was a pattern of increase for those with low motor-function over time. The variability accounted for demonstrated differences with motor-function level (p < 0.05) but not time. Cluster analysis of the pooled synergies highlighted the therapy-induced change in muscle activation. Muscle synergies could be identified for all patients during therapy activities. These results show less complexity and more co-activation in the muscle activation for patients with low motor-function as a higher number of muscle synergies reflects greater movement complexity and task-related phasic muscle activation. The increased number of synergies and changes within synergies by late-therapy suggests improved motor control and movement quality with more distinct phases of movement.

A Longitudinal Electromyography Study of Complex Movements in Poststroke Therapy. 1: Heterogeneous Changes Despite Consistent Improvements in Clinical Assessments.

Poststroke weakness on the more-affected side may arise from reduced corticospinal drive, disuse muscle atrophy, spasticity, and abnormal coordination. This study investigated changes in muscle activation patterns to understand therapy-induced improvements in motor-function in chronic stroke compared to clinical assessments and to identify the effect of motor-function level on muscle activation changes. Electromyography (EMG) was recorded from five upper limb muscles on the more-affected side of 24 patients during early and late therapy sessions of an intensive 14-day program of Wii-based Movement Therapy (WMT) and for a subset of 13 patients at 6-month follow-up. Patients were classified according to residual voluntary motor capacity with low, moderate, or high motor-function levels. The area under the curve was calculated from EMG amplitude and movement duration. Clinical assessments of upper limb motor-function pre- and post-therapy included the Wolf Motor Function Test, Fugl-Meyer Assessment and Motor Activity Log Quality of Movement scale. Clinical assessments improved over time (p < 0.01) with an effect of motor-function level (p < 0.001). The pattern of EMG change by late therapy was complex and variable, with differences between patients with low compared to moderate or high motor-function levels. The area under the curve (p = 0.028) and peak amplitude (p = 0.043) during Wii-tennis backhand increased for patients with low motor-function, whereas EMG decreased for patients with moderate and high motor-function levels. The reductions included movement duration during Wii-golf (p = 0.048, moderate; p = 0.026, high) and Wii-tennis backhand (p = 0.046, moderate; p = 0.023, high) and forehand (p = 0.009, high) and the area under the curve during Wii-golf (p = 0.018, moderate) and Wii-baseball (p = 0.036, moderate). For the pooled data over time, there was an effect of motor-function (p = 0.016) and an interaction between time and motor-function (p = 0.009) for Wii-golf movement duration. Wii-baseball movement duration decreased as a function of time (p = 0.022). There was an effect on Wii-tennis forehand duration for time (p = 0.002), an interaction of time and motor-function (p = 0.005) and an effect of motor-function level on the area under the curve (p = 0.034) for Wii-golf. This study demonstrated different patterns of EMG changes according to residual voluntary motor-function levels, despite heterogeneity within each level that was not evident following clinical assessments alone. Thus, rehabilitation efficacy might be underestimated by analyses of pooled data.

Targeted upper-limb Wii-based Movement Therapy also improves lower-limb muscle activation and functional movement in chronic stroke.

PURPOSE: Post-stroke hemiparesis may manifest as asymmetric gait, poor balance, and inefficient movement patterns. We investigated improvements in lower-limb muscle activation and function during Wii-based Movement Therapy (WMT), a rehabilitation program specifically targeting upper-limb motor-function. METHODS: Electromyography (EMG) was recorded bilaterally from tibialis anterior (TA) in 20 stroke patients during a 14-day WMT program. EMG amplitude and burst duration were analyzed during stereotypical movement sequences of WMT activities. Functional movement ability was assessed pre- and post-therapy including 6-min walk test (6MWT), stair-climbing speed, and Wolf Motor Function Test timed-tasks. RESULTS: TA EMG burst duration during Wii-golf increased by 30% on the more-affected side (p = 0.04) and decreased by 28% on the less-affected side. Patients who did not step during Wii-tennis had a 16% decrease in more-affected TA burst sum (p = 0.047) resulting in more symmetrical activation ratio at late-therapy, with the ratio changing from 3.24 ± 2.25 to 0.99 ± 0.11 (p = 0.047). Six-minute walk and stair-climbing speed improved (p = 0.005 and 0.03, respectively), as did upper-limb movement (p ≤ 0.001). CONCLUSION: This study provides physiological evidence for lower-limb improvements with WMT. Different patterns of muscle activation changes were evident across the WMT activities. Despite the relatively good pre-therapy lower-limb function, muscle activation and symmetry improved significantly with upper-limb WMT. Implications for rehabilitation WMT is an upper-limb neurorehabilitation program that also improves lower-limb motor-function. We report a shift towards more symmetrical muscle activation of tibialis anterior on the more- and less-affected sides that were reflected in increased distance walked during the 6MWT. The use of standing during therapy not only improves lower-limb function but also permits larger and more powerful upper-limb movements. Targeted upper-limb rehabilitation can also significantly improve mobility and balance, whether dynamic or static, that should reduce the risk of falls post-stroke.

BDNF Genotype Interacts with Motor Function to Influence Rehabilitation Responsiveness Poststroke.

BACKGROUND: Persistent motor impairment is common but highly heterogeneous poststroke. Genetic polymorphisms, including those identified on the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes, may contribute to this variability by limiting the capacity for use-dependent neuroplasticity, and hence rehabilitation responsiveness. OBJECTIVE: To determine whether BDNF and APOE genotypes influence motor improvement facilitated by poststroke upper-limb rehabilitation. METHODS: BDNF-Val66Met and APOE isoform genotypes were determined using leukocyte DNA for 55 community-dwelling patients 2-123 months poststroke. All patients completed a dose-matched upper-limb rehabilitation program of either Wii-based Movement Therapy or Constraint-induced Movement Therapy. Upper-limb motor function was assessed pre- and post-therapy using a suite of functional measures. RESULTS: Motor function improved for all patients post-therapy, with no difference between therapy groups. In the pooled data, there was no significant effect of BDNF or APOE genotype on motor function at baseline, or following the intervention. However, a significant interaction between the level of residual motor function and BDNF genotype was identified (p = 0.029), whereby post-therapy improvement was significantly less for Met allele carriers with moderate and high, but not low motor function. There was no significant association between APOE genotype and therapy outcomes. CONCLUSION: This study identified a novel interaction between the BDNF-Val66Met polymorphism, motor-function status, and the magnitude of improvement with rehabilitation in chronic stroke. This polymorphism does not preclude, but may reduce, the magnitude of motor improvement with therapy, particularly for patients with higher, but not lower residual motor function. BDNF genotype should be considered in the design and interpretation of clinical trials.

Cardiovascular fitness is improved post-stroke with upper-limb Wii-based Movement Therapy but not dose-matched constraint therapy.

INTRODUCTION: Post-stroke cardiovascular fitness is typically half that of healthy age-matched people. Cardiovascular deconditioning is a risk factor for recurrent stroke that may be overlooked during routine rehabilitation. This study investigated the cardiovascular responses of two upper limb rehabilitation protocols. METHODS: Forty-six stroke patients completed a dose-matched program of Wii-based Movement Therapy (WMT) or modified Constraint-induced Movement Therapy (mCIMT). Heart rate and stepping were recorded during early (day 2)- and late (day 12-14)-therapy. Pre- and post-therapy motor assessments included the Wolf Motor Function Test and 6-min walk. RESULTS: Upper limb motor function improved for both groups after therapy (WMT p = 0.003, mCIMT p = 0.04). Relative peak heart rate increased from early- to late-therapy WMT by 33% (p < 0.001) and heart rate recovery (HRR) time was 40% faster (p = 0.04). Peak heart rate was higher and HRR faster during mCIMT than WMT, but neither measure changed during mCIMT. Stepping increased by 88% during Wii-tennis (p < 0.001) and 21% during Wii-boxing (p = 0.045) while mCIMT activities were predominantly sedentary. Six-min walk distances increased by 8% (p = 0.001) and 4% (p = 0.02) for WMT and mCIMT, respectively. DISCUSSION: Cardiovascular benefits were evident after WMT as both a cardiovascular challenge and improved cardiovascular fitness. The peak heart rate gradient across WMT activities suggests this therapy can be further individualized to address cardiovascular needs. The mCIMT data suggest a cardiovascular stress response. CONCLUSIONS: This is the first study to demonstrate a cardiovascular benefit during specifically targeted upper limb rehabilitation. Thus, WMT not only improves upper limb motor function but also improves cardiovascular fitness.

The efficacy of Wii-based Movement Therapy for upper limb rehabilitation in the chronic poststroke period: a randomized controlled trial.

BACKGROUND: More effective and efficient rehabilitation is urgently needed to address the prevalence of unmet rehabilitation needs after stroke. This study compared the efficacy of two poststroke upper limb therapy protocols. AIMS AND/OR HYPOTHESIS: We tested the hypothesis that Wii-based movement therapy would be as effective as modified constraint-induced movement therapy for post-stroke upper-limb motor rehabilitation. METHODS: Forty-one patients, 2-46 months poststroke, completed a 14-day program of Wii-based Movement Therapy or modified Constraint-induced Movement Therapy in a dose-matched, assessor-blinded randomized controlled trial, conducted in a research institute or patient's homes. Primary outcome measures were the Wolf Motor Function Test timed-tasks and Motor Activity Log Quality of Movement scale. Patients were assessed at prebaseline (14 days pretherapy), baseline, post-therapy, and six-month follow-up. Data were analyzed using linear mixed models and repeated measures analysis of variance. RESULTS: There were no differences between groups for either primary outcome at any time point. Motor function was stable between prebaseline and baseline (P > 0·05), improved with therapy (P < 0·001); and improvements were maintained at six-months (P > 0·05). Wolf Motor Function Test timed-tasks log times improved from 2·1 ± 0·22 to 1·7 ± 0·22 s after Wii-based Movement Therapy, and 2·6 ± 0·23 to 2·3 ± 0·24 s after modified Constraint-induced Movement Therapy. Motor Activity Log Quality of Movement scale scores improved from 67·7 ± 6·07 to 102·4 ± 6·48 after Wii-based Movement Therapy and 64·1 ± 7·30 to 93·0 ± 5·95 after modified Constraint-induced Movement Therapy (mean ± standard error of the mean). Patient preference, acceptance, and continued engagement were higher for Wii-based Movement Therapy than modified Constraint-induced Movement Therapy. CONCLUSIONS: This study demonstrates that Wii-based Movement Therapy is an effective upper limb rehabilitation poststroke with high patient compliance. It is as effective as modified Constraint-induced Movement Therapy for improving more affected upper limb movement and increased independence in activities of daily living.

Comparison of three tools to measure improvements in upper-limb function with poststroke therapy.

BACKGROUND: Functional ability is regularly monitored poststroke to assess improvement and the efficacy of clinical trials. The balance between implementation times and sensitivity has led to multidomain tools that aim to assess upper-limb function comprehensively. OBJECTIVE: This study implemented 3 common multidomain tools to investigate their suitability across a broad spectrum of movement ability after stroke. METHODS: Forty-nine hemiparetic patients (18 females), aged 22 to 83 years and 24.7 ± 39.2 months poststroke, were assessed before and after a 14-day upper-limb rehabilitation program of Wii-based Movement Therapy. Assessments included the upper-limb motor subscale of the Fugl-Meyer Assessment (F-M), the Wolf Motor Function Test (WMFT), and the Motor Assessment Scale (MAS) upper-limb sections 6 to 8. The MAS was analyzed both with and without the hierarchical system. Patients were stratified with low, moderate, or high motor-function. RESULTS: Upper-limb function improved significantly for the pooled cohort for all assessments (P < .001), although ceiling effects were evident for the F-M, floor effects for the WMFT, and both floor and ceiling effects for MAS. When analyzed by stratified subgroup these improvements were significant for all groups with the F-M, for the moderate and high motor-function groups with both the WMFT and the MAS scored without hierarchical system, but only for the high motor-function group with the hierarchically scored MAS. CONCLUSION: These results suggest that no single test is suitable for measuring function and improvement across the spectrum of poststroke upper-limb dysfunction and that assessment tool selection should be based on the level of residual motor-function of individual patients.

Two common tests of dexterity can stratify upper limb motor function after stroke.

BACKGROUND: Neurological deficits after a stroke are commonly classified according to motor function for clinical decision making regarding discharge and rehabilitation. Participants in clinical stroke studies are also stratified by motor function to avoid a sampling bias. OBJECTIVE: This post hoc analysis examined a suite of upper limb functional assessment tools to test the hypothesis that motor function of survivors of stroke can be stratified using 2 simple tests of manual dexterity despite the heterogeneity of the population. METHODS: The functional ability of the more affected hand and arm was assessed for 67 hemiparetic patients, aged 18 to 83 years (mean ± standard deviation, 59.8 ± 14.0 years), at 1 to 264 months after a stroke (23.6 ± 39.6 months) using the Wolf Motor Function Test (WMFT), upper limb motor Fugl-Meyer Assessment (F-M), Box and Block Test (BBT), grooved pegboard test, and wrist range of motion. We tested the strength of our proposed stratification scheme with a hypothesis-driven hierarchical cluster analysis using standardized raw scores and dichotomous BBT and grooved pegboard test values. RESULTS: The most salient discriminator between low and higher motor function was the ability to move >1 block on the BBT. Within the higher function group, the ability to place all 25 pegs on the grooved pegboard test discriminated between moderate and high motor function. The derived scheme was congruent with clinical observations. The WMFT timed tasks, F-M scores, and range of motion did not discriminate functional groups. CONCLUSIONS: Two simple unambiguous and objective tests of gross (BBT) and fine (grooved pegboard test) manual dexterity discriminated 3 groups of motor function ability for a heterogeneous group of patients after stroke.