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Abstract Stroke is not only associated with muscle weakness, but also associated with reduced muscle fatigue resistance and reduced desaturation during exercise that may be caused by a reduced oxidative capacity and/or microvasculature. Therefore, the objective of the present study was to determine the effects of stroke on muscle mass, fiber size and shape, capillarization and oxidative capacity of the rat m. extensor carpi radialis (ECR) and m. flexor carpi ulnaris (FCU) after a photothrombotic stroke in the forelimb region of the primary sensorimotor cortex. The main observation of the present study was that 4 weeks after induction of stroke there were no significant changes in muscle fiber size and shape. Although there was no significant capillary rarefaction, there was some evidence for remodeling of the capillary bed as reflected by a reduced heterogeneity of capillary spacing (p = 0.006) that may result in improved muscle oxygenation. In the ECR, but not in the FCU, this was accompanied by reduction in muscle fiber oxidative capacity as reflected by reduced optical density of sections stained for succinate dehydrogenase (p = 0.013). The reduced oxidative capacity and absence of significant capillary rarefaction resulted in a capillary to fiber ratio per unit of oxidative capacity that was higher after stroke in the ECR (p = 0.01), but not in the FCU. This suggests that at least during the early stages, stroke is not necessarily accompanied by muscle fiber atrophy, and that stroke‐induced reductions in oxidative capacity resulting in relative excess of capillarization are muscle specific.

BackgroundLower limb motor recovery, including abnormal muscle synergies, occurs mainly within the first 5–8 weeks after a stroke. This suggests the importance of delivering impairment-focused therapies, such as therapeutic robots that promote symmetric gait, during this time-sensitive period, following the principle of “the earlier, the better.”ObjectiveFirst, to compare early robotic training (ERT) with usual care (UC) against UC alone on restoring intralimb muscle synergies and interlimb symmetry during functional tasks; Second, to investigate whether ERT is superior to delayed robotic training (DRT) starting after the proposed time-sensitive period.MethodsThis observer-blinded, randomized pilot trial with crossover design involved 19 nonambulatory adults included within 14 days poststroke. Those allocated to ERT (N = 10) received immediately 4 weeks of training (16 sessions, 4× /week) with the Ekso GT® above UC and were compared with the DRT group (N = 9) who received UC alone at this point. Thereafter a 3-week UC period followed to investigate sustainability of ERT and the interventional roles were exchanged; at about week 8 poststroke DRT subjects started the same experimental robotic protocol and ERT subjects continued UC as controls. Outcomes included changes in Fugl-Meyer lower extremity scores (FM-LE) reflecting muscle synergies, weight-bearing asymmetry (WBA), and dynamic control asymmetry (DCA) during quiet standing. Functional ambulation category (FAC) was used to classify walking independence (cut-off ≥4).ResultsA trend toward earlier reacquisition of walking independence favoring ERT with UC over UC was not accompanied by differences in FM-LE, WBA, or DCA (first objective). Thereafter, DRT with UC did not yield any significant changes relative to UC, such that no between-group differences were found favoring restorative effects of ERT over DRT (second objective).ConclusionThis pilot trial shows the feasibility of investigating a wearable exoskeleton as an adjunct therapy in subacute stroke. Nevertheless, our preliminary findings suggest that motor recovery of lower limb muscle synergies was not enhanced by 4 weeks of robotic training to reduce compensations with the less-affected side, irrespective of the timing of application.Trial registrationClinicalTrials.gov, identifier: NCT03727919.

BackgroundSixty percent of people have non-functional arms 6 months after stroke. More effective treatments are needed. Cochrane Reviews show low-quality evidence that task-specific training improves upper limb function. Our feasibility trial showed 56 h of task-specific training over 6 weeks resulted in an increase of a median 6 points on the Action Research Arm test (ARAT), demonstrating the need for more definitive evidence from a larger randomised controlled trial. Task-AT Home is a two-arm, assessor-blinded, multicentre randomised, controlled study, conducted in the home setting.AimThe objective is to determine whether task-specific training is a more effective treatment than usual care, for improving upper limb function, amount of upper limb use, and health related quality of life at 6 weeks and 6 months after intervention commencement. Our primary hypothesis is that upper limb function will achieve a ≥ 5 point improvement on the ARAT in the task-specific training group compared to the usual care group, after 6 weeks of intervention.MethodsParticipants living at home, with remaining upper limb deficit, are recruited at 3 months after stroke from sites in NSW and Victoria, Australia. Following baseline assessment, participants are randomised to 6 weeks of either task-specific or usual care intervention, stratified for upper limb function based on the ARAT score. The task-specific group receive 14 h of therapist-led task-specific training plus 42 h of guided self-practice. The primary outcome measure is the ARAT at 6 weeks. Secondary measures include the Motor Activity Log (MAL) at 6 weeks and the ARAT, MAL and EQ5D-5 L at 6 months. Assessments occur at baseline, after 6 weeks of intervention, and at 6 months after intervention commencement. Analysis will be intention to treat using a generalised linear mixed model to report estimated mean differences in scores between the two groups at each timepoint with 95% confidence interval and value of p.DiscussionIf the task-specific home-based training programme is more effective than usual care in improving arm function, implementation of the programme into clinical practice would potentially lead to improvements in upper limb function and quality of life for people with stroke.Clinical Trial RegistrationANZCTR.org.au/ACTRN12617001631392p.aspx

Abstract Background Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. Methods The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. Results The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, − 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). Conclusions No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. Trial registration http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013.

Abstract Background Recovery of walking ability is an important goal for patients poststroke, and a basic level of mobility is critical for an early discharge home. Caregiver-mediated exercises could be a resource-efficient strategy to augment exercise therapy and improve mobility in the first months poststroke. A combination of telerehabilitation and face-to-face support, blended care, may empower patient-caregiver dyads and smoothen the transition from professional support to self-management. The Armed4Stroke study aims to investigate the effects of a caregiver-mediated exercise program using a blended care approach in addition to usual care, on recovery of mobility in the first 6 months poststroke. Methods A multicentre, observer-blinded randomized clinical trial in which 74 patient-caregiver dyads will be enrolled in the first 3 months poststroke. Dyads are randomly allocated to a caregiver-mediated exercises intervention or to a control group. The primary endpoint is the self-reported mobility domain of the Stroke Impact Scale. Secondary endpoints include care transition preparedness and psychological functioning of dyads, length of inpatient stay, gait-related measures and extended ADL of patients, and caregiver burden. Outcomes are assessed at enrolment, end of treatment and 6 months follow-up. Results During 8 weeks, caregivers are trained to become an exercise coach using a blended care approach. Dyads will receive a tailor-made, progressive training program containing task-specific exercises focusing on gait, balance, physical activity and outdoor activities. Dyads are asked to perform the training program a minimum of 5 times a week for 30 min per session, supported by a web-based telerehabilitation system with instruction videos and a messaging environment to communicate with their physiotherapist. Conclusions We hypothesize that the Armed4Stroke program will increase self-reported mobility and independence in ADL, facilitating an early discharge poststroke. In addition, we hypothesize that active involvement of caregivers and providing support using blended care, will improve the care transition when professional support tapers off. Therefore, the Armed4Stroke program may complement early supported discharge services. Trial registration Netherlands Trial Register, NL7422 . Registered 11 December 2018.

Abstract Background Smoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a ‘valid’ metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile. Methods The systematic review was performed by screening electronic databases using combined keyword groups Stroke, Reaching and Smoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid. Results The systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, only Spectral Arc Length (SPARC) was found to be a valid metric. Conclusions Based on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.

Abstract Background The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke. Methods Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores. Results SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20], P

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values – an approach that arises in many scientific domains but has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery.

Abstract Background Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting. Design A systematic review using PRISMA and COSMIN guidelines. Methods MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson’s disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires. Results Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population. Conclusion The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.

Fatigue is a common complaint and a disabling symptom among patients following transient ischemic attack (TIA) or minor stroke. In patients with stroke, decreased cardiorespiratory fitness (CRF) is believed to be related to increased severity of post-stroke fatigue (PSF). However, this association between PSF and CRF in patients with TIA or minor stroke has been less investigated, and currently there is no proven treatment for PSF. We aimed to determine the association between PSF and CRF in patients with TIA or minor stroke and to find out whether this association was distorted by confounders. A cross-sectional association study was conducted among a total of 119 patients with TIA or minor stroke. PSF was measured by the Fatigue Severity Scale (FSS) and CRF was quantified by maximal exercise capacity (V̇O2max). The FSS showed a significant association with V̇O2max (ß = −0.061, SE: 0.022; p = 0.007). This association was confounded by anxiety (ß = −0.044, SE: 0.020; p = 0.028) and depression (ß = −0.030, SE: 0.022; p = 0.177) as measured by the subscales of the Hospital Anxiety and Depression Scale (HADS). After controlling for HADS scores on depression and anxiety, the univariate relationship between V̇O2max and FSS was no longer significant. These results suggest that the association between PSF and CRF in patients with TIA or minor stroke is weak and significantly confounded by the factors of depression and anxiety.

IntroductionAlthough most stroke survivors show some spontaneous neurological recovery from motor impairments of the most-affected leg, the contribution of this leg to standing balance control remains often poor. Consequently, it is unclear how spontaneous processes of neurological recovery contributes to early improvements in standing balance.ObjectiveWe aim to investigate (1) the time course of recovery of quiet stance balance control in the first 12 weeks poststroke and (2) how clinically observed improvements of lower limb motor impairments longitudinally relate to this limb's relative contribution to balance control.Methods and AnalysisIn this prospective longitudinal study, a cohort of 60 adults will be recruited within the first 3 weeks after a first-ever hemispheric stroke and mild-to-severe motor impairments. Individual recovery trajectories will be investigated by means of repeated measurements scheduled at 3, 5, 8, and 12 weeks poststroke. The Fugl-Meyer Motor Assessment and Motricity Index of the lower limb serve as clinical measures of motor impairments at the hemiplegic side. As soon as subjects are able to stand independently, bilateral posturography during quietly standing will be measured. First, the obtained center-of-pressure (COP) trajectories at each foot will be used for synchronization and contribution measures that establish (a-)symmetries between lower limbs. Second, the COP underneath both feet combined will be used to estimate overall stability. Random coefficient analyses will be used to model time-dependent changes in these measures and, subsequently, a hybrid model will be used to investigate longitudinal associations with improved motor impairments.DiscussionThe current study aims to investigate how stroke survivors “re-learn” to maintain standing balance as an integral part of daily life activities. The knowledge gained through this study may contribute to recommending treatment strategies for early stroke rehabilitation targeting behavioral restitution of the most-affected leg or learning to compensate with the less-affected leg.

Background The evidence for rehabilitation interventions poststroke lack sufficient robustness. However, variation in treatment effects across countries have been given little attention. Objective To compare two identically protocolized trials conducted in different western countries in order to identify factors that may have caused variation in secondary trial outcomes. Methods Comparative study based on individual patient data (N = 129) from two randomized controlled trials, conducted in hospitals and rehabilitation facilities in the Netherlands (N = 66) and Australia (N = 63). Patients with stroke and their caregivers were randomly allocated to an 8-week caregiver-mediated exercises intervention (N = 63; 31 Australian and 32 Dutch) or to a control group (N = 66; 32 Australian and 34 Dutch). Patient characteristics, compliance, usual care and process measures were compared across countries. We examined if study setting significantly moderated the trial outcomes: Hospital Anxiety and Depression Scale, Fatigue Severity Scale and General Self-Efficacy Scale, measured at 8- and 12 weeks follow-up. In addition, we explored if factors that were significantly different across countries caused variation in these trial outcomes. Results Most patients suffered an ischemic stroke, were in the subacute phase and participated with their partner. Dutch patients were younger (P = 0.005) and had a lower functional status (P = 0.001). Australian patients were recruited earlier poststroke (PConclusions The present study highlighted important clinical differences across countries whilst using an identical study protocol. The observed differences could result in a different potential for recovery and variation in treatment effects across trials. We argue that we can proceed faster to evaluating interventions within international pragmatic trials.

Secondary white matter degeneration is a common occurrence after ischemic stroke, as identified by Diffusion Tensor Imaging (DTI). However, despite recent advances, the time course of the process is not completely understood. The primary aim of this study was to assess secondary degeneration using an approach whereby we create a patient-specific model of damaged fibers based on the volumetric characteristics of lesions. We also examined the effects of secondary degeneration along the modelled streamlines at different distances from the primary infarction using DTI. Eleven patients who presented with upper limb motor deficits at the time of a first-ever ischemic stroke were included. They underwent scanning at weeks 6 and 29 post-stroke. The fractional anisotropy (FA), mean diffusivity (MD), primary eigenvalue (λ1), and transverse eigenvalue (λ23) were measured. Using regions of interest based on the simulation output, the differences between the modelled fibers and matched contralateral areas were analyzed. The longitudinal change between the two time points and across five distances from the primary lesion was also assessed using the ratios of diffusion quantities (rFA, rMD, rλ1, and rλ23) between the ipsilesional and contralesional hemisphere. At week 6 post-stroke, significantly decreased λ1 was found along the ipsilesional corticospinal tract (CST) with a trend towards lower FA, reduced MD and λ23. At week 29 post-stroke, significantly decreased FA was shown relative to the non-lesioned side, with a trend towards lower λ1, unchanged MD, and higher λ23. Along the ipsilesional tract, the rFA diminished, whereas the rMD, rλ1, and rλ23 significantly increased over time. No significant variations in the time progressive effect with distance were demonstrated. The findings support previously described mechanisms of secondary degeneration and suggest that it spreads along the entire length of a damaged tract. Future investigations using higher-order tractography techniques can further explain the intravoxel alterations caused by ischemic injury.

Transcranial direct current stimulation (tDCS) is a promising tool to improve and speed up motor rehabilitation after stroke, but inconsistent clinical effects refrain tDCS from clinical implementation. Therefore, this study aimed to assess the need for individualized tDCS configurations in stroke, considering interindividual variability in brain anatomy and motor function representation.We simulated tDCS in individualized MRI-based finite element head models of 21 chronic stroke subjects and 10 healthy age-matched controls. An anatomy-based stimulation target, i.e. the motor hand knob, was identified with MRI, whereas a motor function-based stimulation target was identified with EEG. For each subject, we simulated conventional anodal tDCS electrode configurations and optimized electrode configurations to maximize stimulation strength within the anatomical and functional target. The normal component of the electric field was extracted and compared between subjects with stroke and healthy, age-matched controls, for both targets, during conventional and optimized tDCS.Electrical field strength was significantly lower, more variable and more frequently in opposite polarity for subjects with stroke compared to healthy age-matched subjects, both for the anatomical and functional target with conventional, i.e. non-individualized, electrode configurations. Optimized, i.e. individualized, electrode configurations increased the electrical field strength in the anatomical and functional target for subjects with stroke but did not reach the same levels as in healthy subjects.Considering individual brain structure and motor function is crucial for applying tDCS in subjects with stroke. Lack of individualized tDCS configurations in subjects with stroke results in lower electric fields in stimulation targets, which may partially explain the inconsistent clinical effects of tDCS in stroke trials.

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception.Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke.Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke.Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke.Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.

Objective: To evaluate the validity of a script concordance test to assess guideline-consistent clinical reasoning by physical therapists in stroke rehabilitation, and to identify critical features of physical therapists specializing in stroke rehabilitation. Methods: A script concordance test was developed according to current standards. Four subgroups of physical therapists (those specializing in neurology, those focusing on neurology or geriatrics, other, and non-specialized undergraduate students) were asked to complete the test. The construct validity of the script concordance test was evaluated with 1-way analysis of variance (ANOVA) to estimate differences between subgroups. Associations between physical therapist characteristics, and script concordance test scores were analysed with bivariate regression analysis followed by multivariate analyses. Results: The script concordance test, with 59 items, was completed by 211 physical therapists. ANOVA analysis showed statistically significant differences between the script concordance test scores of the 4 groups (p

Introduction: Outcome measures are key to tailor rehabilitation goals to the stroke patient's individual needs and to monitor poststroke recovery. The large number of available outcome measures leads to high variability in clinical use. Currently, an internationally agreed core set of motor outcome measures for clinical application is lacking. Therefore, the goal was to develop such a set to serve as a quality standard in clinical motor rehabilitation poststroke.Methods: Outcome measures for the upper and lower extremities, and activities of daily living (ADL)/stroke-specific outcomes were identified and presented to stroke rehabilitation experts in an electronic Delphi study. In round 1, clinical feasibility and relevance of the outcome measures were rated on a 7-point Likert scale. In round 2, those rated at least as “relevant” and “feasible” were ranked within the body functions, activities, and participation domains of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, measurement time points poststroke were indicated. In round 3, answers were reviewed in reference to overall results to reach final consensus.Results: In total, 119 outcome measures were presented to 33 experts from 18 countries. The recommended core set includes the Fugl–Meyer Motor Assessment and Action Research Arm Test for the upper extremity section; the Fugl–Meyer Motor Assessment, 10-m Walk Test, Timed-Up-and-Go, and Berg Balance Scale for the lower extremity section; and the National Institutes of Health Stroke Scale, and Barthel Index or Functional Independence Measure for the ADL/stroke-specific section. The Stroke Impact Scale was recommended spanning all ICF domains. Recommended measurement time points are days 2 ± 1 and 7; weeks 2, 4, and 12; 6 months poststroke and every following 6th month.Discussion and Conclusion: Agreement was found upon a set of nine outcome measures for application in clinical motor rehabilitation poststroke, with seven measurement time points following the stages of poststroke recovery. This core set was specifically developed for clinical practice and distinguishes itself from initiatives for stroke rehabilitation research. The next challenge is to implement this clinical core set across the full stroke care continuum with the aim to improve the transparency, comparability, and quality of stroke rehabilitation at a regional, national, and international level.

Objective: Recovery of the paretic arm post-stroke can be assessed using observational and self-reported measures. The aim of this study was to determine whether the correspondence (match) or non-correspondence (mismatch) between observational and self-reported improvements in upper limb capacity are significantly different at 0–3 months compared with 3–6 months post-stroke. Methods: A total of 159 patients with ischaemic stroke with upper limb paresis were included in the study. Recovery of arm capacity was measured with observational (Action Research Arm Test; ARAT) and self-reported measures (Motor Activity Log Quality of Movement; MAL-QOM and Stroke Impact Scale Hand; SIS-Hand) at 0–3 and 3–6 months post-stroke. The proportion of matches was defined (contingency tables and Fisher’s exact test) and compared across the different time-windows using McNemar’s test. Results: The proportion of matches was not significantly different at 0–3 months compared with 3–6 months post-stroke for the ARAT vs MAL-QOM and SIS-Hand (all p > 0.05). In case of mismatches, patients’ self-reports were more often pessimistic (86%) in the first 3 months post-stroke compared with the subsequent 3 months (39%). Conclusion: The match between observational and self-reported measures of upper limb capacity is not dependent on the timing of assessment post-stroke. Assessment of both observational and self-reported measures may help to recognize possible over- or under-estimation of improvement in upper limb capacity post-stroke.

Abstract Background Transcranial Direct Current Stimulation (tDCS) is an emerging approach for improving capacity in activities of daily living (ADL) and upper limb function after stroke. However, it remains unclear what type of tDCS stimulation is most effective. Our aim was to give an overview of the evidence network regarding the efficacy and safety of tDCS and to estimate the effectiveness of the different stimulation types. Methods We performed a systematic review of randomised trials using network meta-analysis (NMA), searching the following databases until 5 July 2016: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, and four other databases. We included studies with adult people with stroke. We compared any kind of active tDCS (anodal, cathodal, or dual, that is applying anodal and cathodal tDCS concurrently) regarding improvement of our primary outcome of ADL capacity, versus control, after stroke. PROSPERO ID: CRD42016042055. Results We included 26 studies with 754 participants. Our NMA showed evidence of an effect of cathodal tDCS in improving our primary outcome, that of ADL capacity (standardized mean difference, SMD = 0.42; 95% CI 0.14 to 0.70). tDCS did not improve our secondary outcome, that of arm function, measured by the Fugl-Meyer upper extremity assessment (FM-UE). There was no difference in safety between tDCS and its control interventions, measured by the number of dropouts and adverse events. Conclusion Comparing different forms of tDCS shows that cathodal tDCS is the most promising treatment option to improve ADL capacity in people with stroke.

Abstract Background Cortical damage after stroke can drastically impair sensory and motor function of the upper limb, affecting the execution of activities of daily living and quality of life. Motor impairment after stroke has been thoroughly studied, however sensory impairment and its relation to movement control has received less attention. Integrity of the somatosensory system is essential for feedback control of human movement, and compromised integrity due to stroke has been linked to sensory impairment. Methods The goal of this study is to assess the integrity of the somatosensory system in individuals with chronic hemiparetic stroke with different levels of sensory impairment, through a combination of robotic joint manipulation and high-density electroencephalogram (EEG). A robotic wrist manipulator applied continuous periodic disturbances to the affected limb, providing somatosensory (proprioceptive and tactile) stimulation while challenging task execution. The integrity of the somatosensory system was evaluated during passive and active tasks, defined as ‘relaxed wrist’ and ‘maintaining 20% maximum wrist flexion’, respectively. The evoked cortical responses in the EEG were quantified using the power in the averaged responses and their signal-to-noise ratio. Results Thirty individuals with chronic hemiparetic stroke and ten unimpaired individuals without stroke participated in this study. Participants with stroke were classified as having severe, mild, or no sensory impairment, based on the Erasmus modification of the Nottingham Sensory Assessment. Under passive conditions, wrist manipulation resulted in contralateral cortical responses in unimpaired and chronic stroke participants with mild and no sensory impairment. In participants with severe sensory impairment the cortical responses were strongly reduced in amplitude, which related to anatomical damage. Under active conditions, participants with mild sensory impairment showed reduced responses compared to the passive condition, whereas unimpaired and chronic stroke participants without sensory impairment did not show this reduction. Conclusions Robotic continuous joint manipulation allows studying somatosensory cortical evoked responses during the execution of meaningful upper limb control tasks. Using such an approach it is possible to quantitatively assess the integrity of sensory pathways; in the context of movement control this provides additional information required to develop more effective neurorehabilitation therapies.

Introduction: Differentiating between the components of wrist hyper-resistance post stroke, i.e., pathological neuromuscular activation (“spasticity”) and non-neural biomechanical changes, is important for treatment decisions. This study aimed to assess the reliability and construct validity of an innovative measurement device that quantifies these neural and non-neural components by biomechanical modeling.Methods: Forty-six patients with chronic stroke and 30 healthy age-matched subjects were assessed with the NeuroFlexor, a motor-driven device that imposes isokinetic wrist extensions at two controlled velocities (5 and 236°/s). Test-retest reliability was evaluated using intraclass correlation coefficients (ICC) and smallest detectable changes (SDC), and construct validity by testing the difference between patients and healthy subjects and between subgroups of patients stratified by modified Ashworth scale (MAS), and the association with clinical scales.Results: Test-retest reliability was excellent for the neural (NC) and non-neural elastic (EC) components (ICC 0.93 and 0.95, respectively), and good for the viscous component (VC) (ICC 0.84), with SDCs of 10.3, 3.1, and 0.5 N, respectively. NC and EC were significantly higher in patients compared to healthy subjects (p < 0.001). Components gradually increased with MAS category. NC and EC were positively associated with the MAS (rs 0.60 and 0.52, respectively; p < 0.01), and NC with the Tardieu scale (rs 0.36, p < 0.05). NC and EC were negatively associated with the Fugl-Meyer Assessment of the upper extremity and action research arm test (rs ≤ −0.38, p < 0.05).Conclusions: The NeuroFlexor reliably quantifies neural and non-neural components of wrist hyper-resistance in chronic stroke, but is less suitable for clinical evaluation at individual level due to high SDC values. Although construct validity has been demonstrated, further investigation at component level is needed.

Background and purposeWe designed an 8-week caregiver-mediated exercise program with e-health support after stroke (CARE4STROKE) in addition to usual care with the aim to improve functional outcome and to facilitate early supported discharge by increasing the intensity of task specific training.MethodsAn observer-blinded randomized controlled trial in which 66 stroke patient-caregiver couples were included during inpatient rehabilitation. Patients allocated to the CARE4STROKE program trained an additional amount of 150 minutes a week with a caregiver and were compared to a control group that received usual care alone. Primary outcomes: self-reported mobility domain of the Stroke Impact Scale 3.0 (SIS) and length of stay (LOS). Secondary outcomes: motor impairment, strength, walking ability, balance, mobility and (Extended) Activities of Daily Living of patients, caregiver strain of caregivers, and mood, self-efficacy, fatigue and quality of life of both patients and caregivers. Outcomes were assessed at baseline, 8 and 12 weeks after randomization.ResultsNo significant between-group differences were found regarding SIS-mobility after 8 (β 6.21, SD 5.16; P = 0.229) and 12 weeks (β 0.14, SD 2.87; P = 0.961), and LOS (P = 0.818). Significant effects in favor of the intervention group were found for patient's anxiety (β 2.01, SD 0.88; P = 0.023) and caregiver's depression (β 2.33, SD 0.77; P = 0.003) post intervention. Decreased anxiety in patients remained significant at the 12-week follow-up (β 1.01, SD 0.40; P = 0.009).ConclusionsThis proof-of concept trial did not find significant effects on both primary outcomes mobility and LOS as well as the secondary functional outcomes. Treatment contrast in terms of total exercise time may have been insufficient to achieve these effects. However, caregiver-mediated exercises showed a favorable impact on secondary outcome measures of mood for both patient and caregiver.Clinical trial registrationNTR4300, URL- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4300.

Background: Stroke affects the neuronal networks of the non-infarcted hemisphere. The central motor conduction time (CMCT) induced by transcranial magnetic stimulation (TMS) could be used to determine the conduction time of the corticospinal tract of the non-infarcted hemisphere after a stroke. Objectives: Our primary aim was to demonstrate the existence of prolonged CMCT in the non-infarcted hemisphere, measured within the first 48 h when compared to normative data, and secondly, if the severity of motor impairment of the affected upper limb was significantly associated with prolonged CMCTs in the non-infarcted hemisphere when measured within the first 2 weeks post stroke. Methods: CMCT in the non-infarcted hemisphere was measured in 50 patients within 48 h and at 11 days after a first-ever ischemic stroke. Patients lacking significant spontaneous motor recovery, so-called non-recoverers, were defined as those who started below 18 points on the FM-UE and showed less than 6 points (10%) improvement within 6 months. Results: CMCT in the non-infarcted hemisphere was prolonged in 30/50 (60%) patients within 48 h and still in 24/49 (49%) patients at 11 days. Sustained prolonged CMCT in the non-infarcted hemisphere was significantly more frequent in non-recoverers following FM-UE. Conclusions: The current study suggests that CMCT in the non-infarcted hemisphere is significantly prolonged in 60% of severely affected, ischemic stroke patients when measured within the first 48 h post stroke. The likelihood of CMCT is significantly higher in non-recoverers when compared to those that show spontaneous motor recovery early post stroke.

In hemiparetic stroke, functional recovery of paretic limb may occur with the reorganization of neural networks in the brain. Neuroimaging techniques, such as magnetic resonance imaging (MRI), have a high spatial resolution which can be used to reveal anatomical changes in the brain following a stroke. However, low temporal resolution of MRI provides less insight of dynamic changes of brain activity. In contrast, electro-neurophysiological techniques, such as electroencephalography (EEG), have an excellent temporal resolution to measure such transient events, however are hindered by its low spatial resolution. This proof-of-principle study assessed a novel multimodal brain imaging technique namely Variational Bayesian Multimodal Encephalography (VBMEG), which aims to improve the spatial resolution of EEG for tracking the information flow inside the brain and its changes following a stroke. The limitations of EEG are complemented by constraints derived from anatomical MRI and diffusion weighted imaging (DWI). EEG data were acquired from individuals suffering from a stroke as well as able-bodied participants while electrical stimuli were delivered sequentially at their index finger in the left and right hand, respectively. The locations of active sources related to this stimulus were precisely identified, resulting in high Variance Accounted For (VAF above 80%). An accurate estimation of dynamic information flow between sources was achieved in this study, showing a high VAF (above 90%) in the cross-validation test. The estimated dynamic information flow was compared between chronic hemiparetic stroke and able-bodied individuals. The results demonstrate the feasibility of VBMEG method in revealing the changes of information flow in the brain after stroke. This study verified the VBMEG method as an advanced computational approach to track the dynamic information flow in the brain following a stroke. This may lead to the development of a quantitative tool for monitoring functional changes of the cortical neural networks after a unilateral brain injury and therefore facilitate the research into, and the practice of stroke rehabilitation.

Better insight into white matter (WM) alterations after stroke onset could help to understand the underlying recovery mechanisms and improve future interventions. MR diffusion imaging enables to assess such changes. Our goal was to investigate the relation of WM diffusion characteristics derived from diffusion models of increasing complexity with the motor function of the upper limb. Moreover, we aimed to evaluate the variation of such characteristics across different WM structures of chronic stroke patients in comparison to healthy subjects. Subjects were scanned with a two b-value diffusion-weighted MRI protocol to exploit multiple diffusion models: single tensor, single tensor with isotropic compartment, bi-tensor model, bi-tensor with isotropic compartment. From each model we derived the mean tract fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivities outside the lesion site based on a WM tracts atlas. Asymmetry of these measures was correlated with the Fugl-Meyer upper extremity assessment (FMA) score and compared between patient and control groups. Eighteen chronic stroke patients and eight age-matched healthy individuals participated in the study. Significant correlation of the outcome measures with the clinical scores of stroke recovery was found. The lowest correlation of the corticospinal tract FAasymmetry and FMA was with the single tensor model (r = −0.3, p = 0.2) whereas the other models reported results in the range of r = −0.79 ÷ −0.81 and p = 4E-5 ÷ 8E-5. The corticospinal tract and superior longitudinal fasciculus showed most alterations in our patient group relative to controls. Multiple compartment models yielded superior correlation of the diffusion measures and FMA compared to the single tensor model.

To investigate (a) the applicability of the proportional recovery rule of spontaneous neurobiological recovery to motor function of the paretic lower extremity (LE); and (b) the presence of fitters and non-fitters of this prognostic rule poststroke. When present, the clinical threshold for fitting nor non-fitting would be determined, as well as within-subject generalizability to the paretic upper extremity (UE).Prospective cohort study in which the Fugl-Meyer Assessment (FMA)-LE and FMA-UE were measured

BACKGROUND AND PURPOSE:There is growing evidence that visuospatial neglect (VSN) is associated with lower functional performance in other modalities and is not restricted to the lesioned hemisphere alone, and may also affect the non-lesioned hemisphere in severe first-ever strokes. We aimed to investigate the longitudinal association between the severity of VSN, as reflected by the extent of ipsilesional and contralesional spatial attention deficit, and clinical severity of stroke. METHODS:This is a secondary data analysis with merged data from two prospective cohort studies. Resulting in 90 patients and 8 longitudinal measurements at 1, 2, 3, 4, 5, 8, 12, and 26 weeks post-stroke onset. A letter cancellation test (LCT) was used as the primary outcome measure to demonstrate presence and severity of VSN. The clinical severity of stroke was classified using the Bamford Classification. RESULTS:No significant association between clinical severity and the number of ipsilesional, as well as contralesional, omissions on the LCT was observed. Recovery of VSN at the contralesional hemiplegic, as well as ipsilesional non-hemiplegic side, was only dependent on 'time' as a reflection of spontaneous neurobiological recovery post-stroke. The recovery of the ipsilesional extension of VSN was significantly slower for the total anterior circulation infarct (TACI) group compared to the non-TACI group. CONCLUSIONS:Larger strokes have a significant negative impact on recovery of visual attention at the non-hemiplegic side. No clinical determinants that regulate spontaneous time-dependent recovery of VSN were found. While early 'stroke severity' has been regarded as a strong predictor of functional outcome at a group level, other prognostic factors (demographic, stroke related) need to be determined. CLINICAL TRIAL REGISTRATION:EXPLICIT-stroke Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1424 Stroke Intensity Trial: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1665.

Spontaneous motor recovery after stroke appears to be associated with structural and functional changes in the motor network. The aim of the current study was to explore time-dependent changes in resting-state (rs) functional connectivity in motor-impaired stroke patients, using rs-functional MRI at 5 weeks and 26 weeks post-stroke onset. For this aim, 13 stroke patients from the EXPLICIT-stroke Trial and age and gender-matched healthy control subjects were included. Patients' synergistic motor control of the paretic upper-limb was assessed with the upper extremity section of the Fugl-Meyer Assessment (FMA-UE) within 2 weeks, and at 5 and 26 weeks post-stroke onset. Results showed that the ipsilesional rs-functional connectivity between motor areas was lower compared to the contralesional rs-functional connectivity, but this difference did not change significantly over time. No relations were observed between changes in rs-functional connectivity and upper-limb motor recovery, despite changes in upper-limb function as measured with the FMA-UE. Last, overall rs-functional connectivity was comparable for patients and healthy control subjects. To conclude, the current findings did not provide evidence that in moderately impaired stroke patients the lower rs-functional connectivity of the ipsilesional hemisphere changed over time.

OBJECTIVES:Patients without voluntary finger extension early post-stroke are suggested to have a poor prognosis for regaining upper limb capacity at 6 months. Despite this poor prognosis, a number of patients do regain upper limb capacity. We aimed to determine the time window for return of voluntary finger extension during motor recovery and identify clinical characteristics of patients who, despite an initially poor prognosis, show upper limb capacity at 6 months post-stroke. METHODS:Survival analysis was used to assess the time window for return of voluntary finger extension (Fugl-Meyer Assessment hand sub item finger extension≥1). A cut-off of ≥10 points on the Action Research Arm Test was used to define return of some upper limb capacity (i.e. ability to pick up a small object). Probabilities for regaining upper limb capacity at 6 months post-stroke were determined with multivariable logistic regression analysis using patient characteristics. RESULTS:45 of the 100 patients without voluntary finger extension at 8 ± 4 days post-stroke achieved an Action Research Arm Test score of ≥10 points at 6 months. The median time for regaining voluntary finger extension for these recoverers was 4 weeks (lower and upper percentile respectively 2 and 8 weeks). The median time to return of VFE was not reached for the whole group (N = 100). Patients who had moderate to good lower limb function (Motricity Index leg≥35 points), no visuospatial neglect (single-letter cancellation test asymmetry between the contralesional and ipsilesional sides of