Prevalence, patterns, and predictors of patient-reported non-motor outcomes at 30 days after acute stroke: Prospective observational hospital cohort study.

BACKGROUND: Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains. AIMS: We aimed to identify the prevalence, patterns, and the factors associated with non-motor outcomes 30 days after stroke. METHODS: This prospective observational hospital cohort study-Stroke Investigation in North and Central London (SIGNAL)-identified patients with acute ischemic stroke or intracerebral hemorrhage (ICH) admitted to the Hyperacute Stroke Unit (HASU) at University College Hospital (UCH), London, between August 1, 2018 and August 31, 2019. We assessed non-motor outcomes (anxiety, depression, fatigue, sleep, participation in social roles and activities, pain, bowel function, and bladder function) at 30-day follow-up using the Patient-Reported Outcome Measurement Information System-Version 29 (PROMIS-29) scale and Barthel Index scale. RESULTS: We obtained follow-up data for 605/719 (84.1%) eligible patients (mean age 72.0 years; 48.3% female; 521 with ischemic stroke, 84 with ICH). Anxiety (57.0%), fatigue (52.7%), bladder dysfunction (50.2%), reduced social participation (49.2%), and pain (47.9%) were the commonest adverse non-motor outcomes. The rates of adverse non-motor outcomes in ⩾ 1, ⩾ 2 and ⩾ 3 domains were 89%, 66.3%, and 45.8%, respectively; in adjusted analyses, stroke due to ICH (compared to ischemic stroke) and admission stroke severity were the strongest and most consistent predictors. There were significant correlations between bowel dysfunction and bladder dysfunction (κ = 0.908); reduced social participation and bladder dysfunction (κ = 0.844); and anxiety and fatigue (κ = 0.613). We did not identify correlations for other pairs of non-motor domains. CONCLUSION: Adverse non-motor outcomes were very common at 30 days after stroke, affecting nearly 90% of evaluated patients in at least one health domain, about two-thirds in two or more domains, and almost 50% in three or more domains. Stroke due to ICH and admission stroke severity were the strongest and most consistent predictors. Adverse outcomes occurred in pairs of domains, such as with anxiety and fatigue. Our findings emphasize the importance of a multi-domain approach to effectively identify adverse non-motor outcomes after stroke to inform the development of more holistic patient care pathways after stroke.

The impact of brain lesions on tDCS-induced electric fields.

Transcranial direct current stimulation (tDCS) can enhance motor and language rehabilitation after stroke. Though brain lesions distort tDCS-induced electric field (E-field), systematic accounts remain limited. Using electric field modelling, we investigated the effect of 630 synthetic lesions on E-field magnitude in the region of interest (ROI). Models were conducted for two tDCS montages targeting either primary motor cortex (M1) or Broca's area (BA44). Absolute E-field magnitude in the ROI differed by up to 42% compared to the non-lesioned brain depending on lesion size, lesion-ROI distance, and lesion conductivity value. Lesion location determined the sign of this difference: lesions in-line with the predominant direction of current increased E-field magnitude in the ROI, whereas lesions located in the opposite direction decreased E-field magnitude. We further explored how individualised tDCS can control lesion-induced effects on E-field. Lesions affected the individualised electrode configuration needed to maximise E-field magnitude in the ROI, but this effect was negligible when prioritising the maximisation of radial inward current. Lesions distorting tDCS-induced E-field, is likely to exacerbate inter-individual variability in E-field magnitude. Individualising electrode configuration and stimulator output can minimise lesion-induced variability but requires improved estimates of lesion conductivity. Individualised tDCS is critical to overcome E-field variability in lesioned brains.

Spatiotemporal organisation of human sensorimotor beta burst activity.

Beta oscillations in human sensorimotor cortex are hallmark signatures of healthy and pathological movement. In single trials, beta oscillations include bursts of intermittent, transient periods of high-power activity. These burst events have been linked to a range of sensory and motor processes, but their precise spatial, spectral, and temporal structure remains unclear. Specifically, a role for beta burst activity in information coding and communication suggests spatiotemporal patterns, or travelling wave activity, along specific anatomical gradients. We here show in human magnetoencephalography recordings that burst activity in sensorimotor cortex occurs in planar spatiotemporal wave-like patterns that dominate along two axes either parallel or perpendicular to the central sulcus. Moreover, we find that the two propagation directions are characterised by distinct anatomical and physiological features. Finally, our results suggest that sensorimotor beta bursts occurring before and after a movement can be distinguished by their anatomical, spectral, and spatiotemporal characteristics, indicating distinct functional roles.

Real-time auditory feedback may reduce abnormal movements in patients with chronic stroke.

PURPOSE: The current pilot study assesses the use of real-time auditory feedback to help reduce abnormal movements during an active reaching task in patients with chronic stroke. MATERIALS AND METHODS: 20 patients with chronic stroke completed the study with full datasets (age: M = 53 SD = 14; sex: male = 75%; time since stroke in months: M = 34, SD = 33). Patients undertook 100 repetitions of an active reaching task while listening to self-selected music which automatically muted when abnormal movement was detected, determined by thresholds set by clinical therapists. A within-subject design with two conditions (with auditory feedback vs. without auditory feedback) presented in a randomised counterbalanced order was used. The dependent variable was the duration of abnormal movement as a proportion of trial duration. RESULTS: A significant reduction in the duration of abnormal movement was observed when patients received auditory feedback, F(1,18) = 9.424, p = 0.007, with a large effect size (partial η2 = 0.344). CONCLUSIONS: Patients with chronic stroke can make use of real-time auditory feedback to increase the proportion of time they spend in optimal movement patterns. The approach provides a motivating framework that encourages high dose with a key focus on quality of movement. Trial Registration: ISRCTN12969079 https://www.isrctn.com/ISRCTN12969079 ISRTCN trial registration REF: ISRCTN12969079IMPLICATIONS FOR REHABILITATIONMovement quality during upper limb rehabilitation should be targeted as part of a well-balanced rehabilitation programme.Auditory feedback is a useful tool to help patients with chronic stroke reduce compensatory movements.

Optimising rehabilitation and recovery after a stroke.

Stroke can cause significant disability and impact quality of life. Multidisciplinary neurorehabilitation that meets individual needs can help to optimise recovery. Rehabilitation is essential for best quality care but should start early, be ongoing and involve effective teamwork. We describe current stroke rehabilitation processes, from the hyperacute setting through to inpatient and community rehabilitation, to long-term care and report on which UK quality care standards are (or are not) being met. We also examine the gap between what stroke rehabilitation is recommended and what is being delivered, and suggest areas for further improvement.

Biomarkers of plasticity for stroke recovery.

Stroke is the commonest cause of physical disability in the world. Our understanding of the biologic mechanisms involved in recovery and repair has advanced to the point that therapeutic opportunities to promote recovery through manipulation of post-stroke plasticity have never been greater. This work has almost exclusively been carried out in rodent models of stroke with little translation into human studies. The challenge ahead is to develop a mechanistic understanding of recovery from stroke in humans. Advances in neuroimaging techniques can now provide the appropriate intermediate level of description to bridge the gap between a molecular and cellular account of recovery and a behavioral one. Clinical trials can then be designed in a stratified manner taking into account when an intervention should be delivered and who is most likely to benefit. This approach is most likely to lead to the step-change in how restorative therapeutic strategies are delivered in human stroke patients.

EEG Fractal Analysis Reflects Brain Impairment after Stroke.

Stroke is the commonest cause of disability. Novel treatments require an improved understanding of the underlying mechanisms of recovery. Fractal approaches have demonstrated that a single metric can describe the complexity of seemingly random fluctuations of physiological signals. We hypothesize that fractal algorithms applied to electroencephalographic (EEG) signals may track brain impairment after stroke. Sixteen stroke survivors were studied in the hyperacute (<48 h) and in the acute phase (∼1 week after stroke), and 35 stroke survivors during the early subacute phase (from 8 days to 32 days and after ∼2 months after stroke): We compared resting-state EEG fractal changes using fractal measures (i.e., Higuchi Index, Tortuosity) with 11 healthy controls. Both Higuchi index and Tortuosity values were significantly lower after a stroke throughout the acute and early subacute stage compared to healthy subjects, reflecting a brain activity which is significantly less complex. These indices may be promising metrics to track behavioral changes in the very early stage after stroke. Our findings might contribute to the neurorehabilitation quest in identifying reliable biomarkers for a better tailoring of rehabilitation pathways.

Brain Plasticity Mechanisms Underlying Motor Control Reorganization: Pilot Longitudinal Study on Post-Stroke Subjects.

Functional Electrical Stimulation (FES) has demonstrated to improve walking ability and to induce the carryover effect, long-lasting persisting improvement. Functional magnetic resonance imaging has been used to investigate effective connectivity differences and longitudinal changes in a group of chronic stroke patients that attended a FES-based rehabilitation program for foot-drop correction, distinguishing between carryover effect responders and non-responders, and in comparison with a healthy control group. Bayesian hierarchical procedures were employed, involving nonlinear models at within-subject level-dynamic causal models-and linear models at between-subjects level. Selected regions of interest were primary sensorimotor cortices (M1, S1), supplementary motor area (SMA), and angular gyrus. Our results suggest the following: (i) The ability to correctly plan the movement and integrate proprioception information might be the features to update the motor control loop, towards the carryover effect, as indicated by the reduced sensitivity to proprioception input to S1 of FES non-responders; (ii) FES-related neural plasticity supports the active inference account for motor control, as indicated by the modulation of SMA and M1 connections to S1 area; (iii) SMA has a dual role of higher order motor processing unit responsible for complex movements, and a superintendence role in suppressing standard motor plans as external conditions changes.

Sensorimotor cortex beta oscillations reflect motor skill learning ability after stroke.

Recovery of skilled movement after stroke is assumed to depend on motor learning. However, the capacity for motor learning and factors that influence motor learning after stroke have received little attention. In this study, we first compared motor skill acquisition and retention between well-recovered stroke patients and age- and performance-matched healthy controls. We then tested whether beta oscillations (15-30 Hz) from sensorimotor cortices contribute to predicting training-related motor performance. Eighteen well-recovered chronic stroke survivors (mean age 64 ± 8 years, range: 50-74 years) and 20 age- and sex-matched healthy controls were trained on a continuous tracking task and subsequently retested after initial training (45-60 min and 24 h later). Scalp electroencephalography was recorded during the performance of a simple motor task before each training and retest session. Stroke patients demonstrated capacity for motor skill learning, but it was diminished compared to age- and performance-matched healthy controls. Furthermore, although the properties of beta oscillations prior to training were comparable between stroke patients and healthy controls, stroke patients did show less change in beta measures with motor learning. Lastly, although beta oscillations did not help to predict motor performance immediately after training, contralateral (ipsilesional) sensorimotor cortex post-movement beta rebound measured after training helped predict future motor performance, 24 h after training. This finding suggests that neurophysiological measures such as beta oscillations can help predict response to motor training in chronic stroke patients and may offer novel targets for therapeutic interventions.

Blowing up Neural Repair for Stroke Recovery: Preclinical and Clinical Trial Considerations.

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points.

Welcoming back my arm: affective touch increases body ownership following right-hemisphere stroke.

Right-hemisphere stroke can impair the ability to recognize one's contralesional body parts as belonging to one's self. The study of this so-called 'disturbed sense of limb ownership' can provide unique insights into the neurocognitive mechanisms of body ownership. In this study, we address a hypothesis built upon experimental studies on body ownership in healthy volunteers. These studies have shown that affective (pleasant) touch, an interoceptive modality associated with unmyelinated, slow-conducting C-tactile afferents, has a unique role in the sense of body ownership. In this study, we systematically investigated whether affective touch stimulation could increase body ownership in patients with a disturbed sense of limb ownership following right-hemisphere stroke. An initial feasibility study in 16 adult patients with acute stroke enabled us to optimize and calibrate an affective touch protocol to be administered by the bedside. The main experiment, conducted with a different sample of 26 right hemisphere patients, assessed changes in limb ownership elicited following self- (patient) versus other- (experimenter) generated tactile stimulation, using a velocity known to optimally activate C-tactile fibres (i.e. 3 cm/s), and a second velocity that is suboptimal for C-tactile activation (i.e. 18 cm/s). We further examined the specificity and mechanism of observed changes in limb ownership in secondary analyses looking at (i) the influence of perceived intensity and pleasantness of touch, (ii) touch laterality and (iii) level of disturbed sense of limb ownership on ownership change and (iv) changes in unilateral neglect arising from touch. Findings indicated a significant increase in limb ownership following experimenter-administered, C-tactile-optimal touch. Voxel-based lesion-symptom mapping identified damage to the right insula and, more substantially, the right corpus callosum, associated with a failure to increase body ownership following experimenter-administered, affective touch. Our findings suggest that affective touch can increase the sense of body-part ownership following right-hemisphere stroke, potentially due to its unique role in the multisensory integration processes that underlie the sense of body ownership.

Dissecting Transient Burst Events.

Increasing efforts are being made to understand the role of intermittent, transient, high-power burst events of neural activity. These events have a temporal, spectral, and spatial domain. Here, we argue that considering all three domains is crucial to fully reveal the functional relevance of these events in health and disease.

The key features and role of peer support within group self-management interventions for stroke? A systematic review.

Purpose: To assess the key features of group self-management interventions for stroke and explore the role of peer support in this setting.Method: A segregated mixed research synthesis was conducted. A literature search was performed in OvidSP, EMBASE, AMED and EBSCO (up to January 2018). Studies were included if they delivered group interventions containing self-management principles to stroke survivors on more than two consecutive occasions. The bias of included studies was assessed using NICE guidelines. Quantitative data were analyzed using frequency counts and qualitative data were analyzed thematically.Results: Twelve studies were included in the review including a total of 3298 participants (age range 56-89) and eight different self-management interventions. Key features of group self-management interventions were identified as increasing knowledge, collaboration and/or communication, accessing resources, goal setting, and problem solving. Peer support facilitated the sharing of experiences, social comparison, vicarious learning, and increased motivation.Conclusion: Future self-management interventions should be designed to maximize peer support and incorporate techniques which facilitate, knowledge building, goal setting, access to resources, problem solving, and communication.Implications for rehabilitationGroup self-management interventions offer a way to provide peer support to stroke survivors and should be utilized in practice.Peer support is seen by stroke survivors as valuable because it can facilitate the sharing of experiences, social comparison, vicarious learning, and increase motivation.Knowledge building, goal setting, problem solving, collaborative skills, and the ability to access resources should be incorporated into interventions aiming to enhance self-management behaviors in the stroke population.

A Stroke Recovery Trial Development Framework: Consensus-Based Core Recommendations from the Second Stroke Recovery and Rehabilitation Roundtable.

A major goal of the Stroke Recovery and Rehabilitation Roundtable (SRRR) is to accelerate development of effective treatments to enhance stroke recovery beyond that expected to occur spontaneously or with current approaches. In this paper, we describe key issues for the next generation of stroke recovery treatment trials and present the Stroke Recovery and Rehabilitation Roundtable Trials Development Framework (SRRR-TDF). An exemplar (an upper limb recovery trial) is presented to demonstrate the utility of this framework to guide the GO, NO-GO decision-making process in trial development.

A stroke recovery trial development framework: Consensus-based core recommendations from the Second Stroke Recovery and Rehabilitation Roundtable.

A major goal of the Stroke Recovery and Rehabilitation Roundtable (SRRR) is to accelerate development of effective treatments to enhance stroke recovery beyond that expected to occur spontaneously or with current approaches. In this paper, we describe key issues for the next generation of stroke recovery treatment trials and present the Stroke Recovery and Rehabilitation Roundtable Trials Development Framework (SRRR-TDF). An exemplar (an upper limb recovery trial) is presented to demonstrate the utility of this framework to guide the GO, NO-GO decision-making process in trial development.

A systematic review protocol of timing, efficacy and cost effectiveness of upper limb therapy for motor recovery post-stroke.

BACKGROUND: Improving upper limb (UL) motor recovery after stroke represents a major clinical and scientific goal. We aim to complete three systematic reviews to estimate the (1) association between time to start of UL therapy and motor recovery, (2) relative efficacy of different UL therapy approaches post-stroke and (3) cost-effectiveness of UL therapy interventions. METHODS: We have designed a systematic review protocol to address three systematic review questions that were each registered with PROSPERO. The search will be conducted in MEDLINE, EMBASE, and Cochrane Controlled Register of Trials. We will include randomised controlled trials, non-randomised clinical trials, before-after studies and observational studies of adult stroke survivors with an average stroke onset < 6 months, undergoing hospital-based therapy to improve UL function. Eligible interventions will aim to promote UL functional recovery. Two reviewers will independently screen, select and extract data. Study risk of bias will be appraised using appropriate tools. Clinical measures of motor recovery will be investigated (primary measure Fugl Meyer UL assessment), as well as measures of health-related quality of life (primary measure EQ-5D) and all cost-effectiveness analyses completed. Secondary outcomes include therapy dose (minutes, weeks, repetitions as available) and safety (i.e. adverse events, serious adverse events). A narrative synthesis will describe quality and content of the evidence. If feasible, we will conduct random effects meta-analyses where appropriate. DISCUSSION: We anticipate the findings of this review will increase our understanding of UL therapy and inform the generation of novel, data-driven hypotheses for future UL therapy research post-stroke. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018019367, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111629, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111628.

Cortical beta oscillations are associated with motor performance following visuomotor learning.

People vary in their capacity to learn and retain new motor skills. Although the relationship between neuronal oscillations in the beta frequency range (15-30 Hz) and motor behaviour is well established, the electrophysiological mechanisms underlying individual differences in motor learning are incompletely understood. Here, we investigated the degree to which measures of resting and movement-related beta power from sensorimotor cortex account for inter-individual differences in motor learning behaviour in the young and elderly. Twenty young (18-30 years) and twenty elderly (62-77 years) healthy adults were trained on a novel wrist flexion/extension tracking task and subsequently retested at two different time points (45-60 min and 24 h after initial training). Scalp EEG was recorded during a separate simple motor task before each training and retest session. Although short-term motor learning was comparable between young and elderly individuals, there was considerable variability within groups with subsequent analysis aiming to find the predictors of this variability. As expected, performance during the training phase was the best predictor of performance at later time points. However, regression analysis revealed that movement-related beta activity significantly explained additional variance in individual performance levels 45-60 min, but not 24 h after initial training. In the context of disease, these findings suggest that measurements of beta-band activity may offer novel targets for therapeutic interventions designed to promote rehabilitative outcomes.

Intensive upper limb neurorehabilitation in chronic stroke: outcomes from the Queen Square programme.

OBJECTIVE: Persistent difficulty in using the upper limb remains a major contributor to physical disability post-stroke. There is a nihilistic view about what clinically relevant changes are possible after the early post-stroke phase. The Queen Square Upper Limb Neurorehabilitation programme delivers high-quality, high-dose, high-intensity upper limb neurorehabilitation during a 3-week (90 hours) programme. Here, we report clinical changes made by the chronic stroke patients treated on the programme, factors that might predict responsiveness to therapy and the relationship between changes in impairment and activity. METHODS: Upper limb impairment and activity were assessed on admission, discharge, 6 weeks and 6 months after treatment, with modified upper limb Fugl-Meyer (FM-UL, max-54), Action Research Arm Test (ARAT, max-57) and Chedoke Arm and Hand Activity Inventory (CAHAI, max-91). Patient-reported outcome measures were recorded with the Arm Activity Measure (ArmA) parts A (0-32) and B (0-52), where lower scores are better. RESULTS: 224 patients (median time post-stroke 18 months) completed the 6-month programme. Median scores on admission were as follows: FM-UL = 26 (IQR 16-37), ARAT=18 (IQR 7-33), CAHAI=40 (28-55), ArmA-A=8 (IQR 4.5-12) and ArmA-B=38 (IQR 24-46). The median scores 6 months after the programme were as follows: FM-UL=37 (IQR 24-48), ARAT=27 (IQR 12-45), CAHAI=52 (IQR 35-77), ArmA-A=3 (IQR 1-6.5) and ArmA-B=19 (IQR 8.5-32). We found no predictors of treatment response beyond admission scores. CONCLUSION: With intensive upper limb rehabilitation, chronic stroke patients can change by clinically important differences in measures of impairment and activity. Crucially, clinical gains continued during the 6-month follow-up period.