Timing and Dose of Upper Limb Motor Intervention After Stroke: A Systematic Review.

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22-66) and study sample size remains small (median n=30, IQR 20-48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1-7 days), 176 early subacute (8-90 days), 34 late subacute (91-180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600-1430) min/session, 1 (IQR, 1-1) session/d, 5 (IQR, 5-5) d/wk for 4 (IQR, 3-5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629.

Determining Maximal Tolerable Aerobic Training Intensity in the Acute Phase after Stroke: a Novel Dose Ranging Trial Protocol.

INTRODUCTION: There is strong evidence that cardiorespiratory fitness (CRF) training improves fitness and mobility after stroke. Despite the large number of studies, the most efficacious dose is yet to be determined. Furthermore, the safety of early post-stroke training, while theoretically beneficial, remains uncertain. The aim of this study is to determine the maximum safe and tolerable intensity of CRF training early post-stroke. METHODS: This is a stratified (low to moderate exercise capacity), Phase I, 5+5 dose ranging trial protocol. Participants will be recruited within one month post-stroke and stratified by their exercise-capacity (i.e. low and moderate capacity). Cohorts of five participants will perform 12 interval-based training sessions for four-weeks at a pre-determined target-intensity. The intensity will increase in each consecutive cohort, in each stratum according to pre-defined rules until the maximum safe and tolerable intensity is reached, as determined by the occurrence of dose-limiting events and occurrence of adverse events. Dose-limiting events are defined as symptoms indicative of over-training including pain and inability to perform usual activities. STUDY OUTCOME: Maximum safe and tolerable intensity of CRF training in stroke survivors with low and moderate exercise capacity. DISCUSSION: This study is a first step in the systematic development of a CRF training intervention. We believe similar dose ranging designs may be useful for development of other rehabilitation interventions in different study populations.

Safety of Performing a Graded Exercise Test Early after Stroke and Transient Ischemic Attack.

BACKGROUND: Low cardiorespiratory fitness (CRF) is a predictor of stroke risk and poor outcome poststroke. Fitness levels are rarely assessed in the acute phase and it is unclear if it is safe for stroke survivors and people with transient ischemic attack (TIA) to perform a graded exercise test to assess fitness. OBJECTIVE: To determine if people within 14 days post stroke can safely perform a graded exercise test. DESIGN: Observational study. SETTING: Research institute. PARTICIPANTS: People with stroke or TIA admitted to an acute stroke unit. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Safety of performing a graded exercise test early post stroke. Safety outcomes were (1) occurrence of an adverse event or (2) <85% blood oxygen saturation (SpO2 ). Participants performed a graded exercise test on a recumbent stepper at a research institute <2 weeks postevent. CRF was determined by measuring peak volume of oxygen uptake (VO2peak ) using a metabolic cart. RESULTS: Twenty-nine participants were enrolled in the study (median age 69 years; interquartile range 58-75). Sixteen were diagnosed with TIA and 13 with a mild stroke. Twenty-eight participants completed the test; one participant was unable to perform the test due to back pain. The test was terminated due to standardized stopping criteria in 26 cases (5 = volitional fatigue, 6 = unable to keep required cadence, 15 = reaching 85% HRmax ), one due to safety (ie, SpO2 < 85%), and one was inadvertently terminated before stopping criteria were reached. Average CRF determined by the exercise test was low; mean VO2peak of 16.2 ± 4.5 mL/kg/min for men (n = 20) and 12.4 ± 3.6 mL/kg/min for women (n = 8). CONCLUSIONS: Determining exercise capacity early post stroke and TIA using a graded exercise test appears to be safe in patients with mild deficits. This information should be useful to plan tailored exercise programs. Further research should focus on determining safety of exercise testing in more severely affected stroke survivors.

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.

Early Mobilization After Stroke Is Not Associated With Cognitive Outcome.

Background and Purpose- We aimed to determine whether early mobilization after stroke affects subsequent cognitive function. Methods- AVERT (A Very Early Rehabilitation Trial) was an international, 56-site, phase 3 randomized controlled trial, conducted from 2006 to 2015. Participants were included if they were aged 18+, presented within 24 hours of stroke, and satisfied physiological limits for blood pressure, heart rate, and temperature. Participants were randomized to receive either usual stroke unit care or very early and more frequent mobilization in addition to usual stroke unit care. The Montreal Cognitive Assessment, scored 0 to 30, was introduced as a 3-month outcome during 2008. Results- Of the 2104 patients included in AVERT, 317 were assessed before the Montreal Cognitive Assessment's introduction. Of the remaining 1787, 1189 (66.5%) had complete Montreal Cognitive Assessment data, 456 (25.5%) had partially or completely missing data, 136 (7.6%) had died, and 6 (0.3%) were lost to follow-up. In surviving participants with complete data, adjusting for age and stroke severity, total Montreal Cognitive Assessment score was no different in the intervention (n=595; median, 23; interquartile range, 19-26; mean, 21.9; SD, 5.9) and usual care (n=594; median, 23; interquartile range, 19-26; mean, 21.8; SD, 5.9) groups ( P=0.68). Conclusions- Exposure to earlier and more frequent mobilization in the acute stage of stroke does not influence cognitive outcome at 3 months. This stands in contrast to the primary outcome from AVERT (modified Rankin Scale), where the intervention group had less favorable outcomes than controls. Clinical Trial Registration- URL: https://www.anzctr.org.au . Unique identifier: ACTRN12606000185561.

The prevalence of fatigue after stroke: A systematic review and meta-analysis.

BACKGROUND: Fatigue is a common and debilitating symptom after stroke. The last decade has seen rapid expansion of the research literature on post-stroke fatigue, but prevalence remains unclear. AIMS: To estimate post-stroke fatigue prevalence and to identify the contributing factors to fatigue, by conducting a systematic review and meta-analysis. SUMMARY OF REVIEW: We included all studies of adult stroke survivors that used a recognized assessment scale for fatigue (search date September 2014). Two reviewers independently reviewed all full texts for inclusion. Data were extracted by one reviewer and independently cross-checked by a second. Risk of bias was evaluated using a critical appraisal tool. From an overall yield of 921 studies, 101 full text papers were screened, and 49 of these met inclusion criteria. The most widely used measure of fatigue was the Fatigue Severity Scale (n = 24 studies). Prevalence estimates at a cut-off score of > or ≥ 4 were available for 22 of these 24 studies (total n = 3491), and ranged from 25 to 85%. In random effects meta-analysis, the pooled prevalence estimate was 50% (95% CI 43-57%), with substantial heterogeneity (I2 = 94%). Neither depression status nor time point post-stroke explained the heterogeneity between studies. In post-hoc analysis, fatigue prevalence was found to be lower in the four Asian studies (35%; 95% CI 20-50; I2 = 96%). CONCLUSIONS: Our results confirm that fatigue is a widespread issue for stroke survivors, although it may be less prevalent in Asia. Further research is needed to explain the wide variability in prevalence estimates between studies.

Measuring activity levels at an acute stroke ward: comparing observations to a device.

BACKGROUND: If a simple system of instrumented monitoring was possible early after stroke, therapists may be able to more readily gather information about activity and monitor progress over time. Our aim was to establish whether a device containing a dual-axis accelerometer provides similar information to behavioural mapping on physical activity patterns early after stroke. METHODS: Twenty participants with recent stroke ≤ 2 weeks and aged >18 were recruited and monitored at an acute stroke ward. The monitoring device (attached to the unaffected leg) and behavioural mapping (observation) were simultaneously applied from 8 a.m. to 5 p.m. Both methods recorded the time participants spent lying, sitting, and upright. RESULTS: The median percentage and interquartile range (IQR) of time spent lying, sitting, and upright recorded by the device were 36% (15-68), 51% (28-72), and 2% (1-5), respectively. Agreement between the methods was substantial: Intraclass Correlation Coefficient (95% CI): lying 0.74 (0.46-0.89), sitting 0.68 (0.36-0.86), and upright 0.72 (0.43-0.88). CONCLUSION: Patients are inactive in an acute stroke setting. In acute stroke, estimates of time spent lying, sitting, and upright measured by a device are valid.

Changes in activity levels in the first month after stroke.

[Purpose] To quantify the activity levels of individuals in an acute stroke ward, and to determine if their activity levels change within the first month after stroke. [Methods] In this pilot study, participant activity was monitored prospectively over a single day from 8 a.m. to 5 p.m. on two separate occasions. Individuals with confirmed stroke > 18 years of age and less than 15 days post-stroke at the time of recruitment were eligible for inclusion in this study. Activity was recorded using an electronic device. The first day was scheduled within 15 days and the second at four weeks post-stroke. We looked at the following activity categories: number of transitions, and the times spent lying, sitting and in dynamic activity. [Results] Sixteen individuals were included in this study with a median age of 79.5 years (interquartile range 62.5 to 85). Fifty-six % of the participants had mild, 31% had moderate and 13% had severe stroke, according to the NIHSS score. There were no significant changes in number of transitions, or times spent in dynamic activity and lying and sitting. [Conclusion] Activity levels were low at an acute stroke ward and did not significantly change within the first month.

Self-report fatigue questionnaires in multiple sclerosis, Parkinson's disease and stroke: a systematic review of measurement properties.

PURPOSE: To critically appraise, compare and summarize the measurement properties of self-report fatigue questionnaires validated in patients with multiple sclerosis (MS), Parkinson's disease (PD) or stroke. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL and SPORTdiscus were searched. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of studies. A qualitative data synthesis was performed to rate the measurement properties for each questionnaire. RESULTS: Thirty-eight studies out of 5,336 records met the inclusion criteria, evaluating 31 questionnaires. Moderate evidence was found for adequate internal consistency and structural validity of the Fatigue Scale for Motor and Cognitive functions (FSMC) and for adequate reliability and structural validity of the Unidimensional Fatigue Impact Scale (U-FIS) in MS. CONCLUSIONS: We recommend the FSMC and U-FIS in MS. The Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F) and Fatigue Severity Scale (FSS) show promise in PD, and the Profile of Mood States Fatigue subscale (POMS-F) for stroke. Future studies should focus on measurement error, responsiveness and interpretability. Studies should also put emphasis on providing input for the theoretical construct of fatigue, allowing the development of questionnaires that reflect generic and disease-specific symptoms of fatigue.