A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke.

The aim of this prospective observational longitudinal study was to explore and decipher the predictive value of prospective MRI biomarkers in the brain and lower limb muscles for 3-month lower limb motor recovery following stroke. In the brain, we measured the integrity of the corticospinal tract (fractional anisotropy/"FA"). In the muscles, we measured volume, fatty replacement (fat fraction analysis and proton spectroscopy) and oedema. Measurements were taken at two time points: (1) within 4 weeks of stroke (baseline measurement, clinical and imaging) and (2) 3 months following stroke (follow up measurement, clinical only). Clinical measurements consisted of assessments of functional ability and strength (Fugl-Meyer score, motor NIHSS, Functional Ambulation Category/"FAC", and muscle dynamometry). Twenty-three patients completed imaging and clinical assessments at baseline and follow-up; five patients had partial imaging assessment. The results provided some evidence that damage to the corticospinal tract would result in less motor recovery: recovery of the Fugl-Meyer score and dynamometric ankle plantarflexion, ankle dorsiflexion, and knee extension correlated positively and significantly with fractional anisotropy (0.406-0.457; p = 0.034-p = 0.016). However, fractional anisotropy demonstrated a negative correlation with recovery of the Functional Ambulation Category (-0.359, p = 0.046). For the muscle imaging, significant inverse correlation was observed between vastus lateralis fat fraction vs. NIHSS recovery (-0.401, p = 0.04), and a strong positive correlation was observed between ratio of intra- to extra-myocellular lipid concentrations and the recovery of knee flexion (0.709, p = 0.007). This study supports previous literature indicating a positive correlation between the integrity of the corticospinal tract and motor recovery post-stroke, expanding the limited available literature describing this relationship specifically for the lower limb. However, recovery of functional ambulation behaved differently to other clinical recovery markers by demonstrating an inverse relationship with corticospinal tract integrity. The study also introduces some muscle imaging biomarkers as potentially valuable in the prediction of 3-month lower limb motor recovery following stroke.

Auditory rhythmical cueing to improve gait in community-dwelling stroke survivors (ACTIVATE): a pilot randomised controlled trial.

BACKGROUND: Gait impairment limiting mobility and restricting activities is common after stroke. Auditory rhythmical cueing (ARC) uses a metronome beat delivered during exercise to train stepping and early work reports gait improvements. This study aimed to establish the feasibility of a full scale multicentre randomised controlled trial to evaluate an ARC gait and balance training programme for use by stroke survivors in the home and outdoors. METHODS: A parallel-group observer-blind pilot randomised controlled trial was conducted. Adults within 2 years of stroke with a gait-related mobility impairment were recruited from four NHS stroke services and randomised to an ARC gait and balance training programme (intervention) or the training programme without ARC (control). Both programmes consisted of 3x30 min sessions per week for 6 weeks undertaken at home/nearby outdoor community. One session per week was supervised and the remainder self-managed. Gait and balance performance assessments were undertaken at baseline, 6 and 10 weeks. Key trial outcomes included recruitment and retention rates, programme adherence, assessment data completeness and safety. RESULTS: Between November 2018 and February 2020, 59 participants were randomised (intervention n=30, control n=29), mean recruitment rate 4/month. At baseline, 6 weeks and 10 weeks, research assessments were conducted for 59/59 (100%), 47/59 (80%) and 42/59 (71%) participants, respectively. Missing assessments were largely due to discontinuation of data collection from mid-March 2020 because of the UK COVID-19 pandemic lockdown. The proportion of participants with complete data for each individual performance assessment ranged from 100% at baseline to 68% at 10 weeks. In the intervention group, 433/540 (80%) total programme exercise sessions were undertaken, in the control group, 390/522 (75%). Falls were reported by five participants in the intervention group, six in the control group. Three serious adverse events occurred, all unrelated to the study. CONCLUSION: We believe that a definitive multicentre RCT to evaluate the ARC gait and balance training programme is feasible. Recruitment, programme adherence and safety were all acceptable. Although we consider that the retention rate and assessment data completeness were not sufficient for a future trial, this was largely due to the UK COVID-19 pandemic lockdown. TRIAL REGISTRATION: ISRCTN, ISRCTN10874601 , Registered on 05/03/2018.

Feasibility, acceptability, and fidelity of Physical Activity Routines After Stroke (PARAS): a multifaceted behaviour change intervention targeting free-living physical activity and sedentary behaviour in community-dwelling adult stroke survivors.

BACKGROUND: Low levels of habitual physical activity and high levels of sedentary behaviour are commonly observed post-stroke. We aimed to assess the feasibility, acceptability and fidelity of a multifaceted, theory- and evidence-informed supported self-management intervention targeting physical activity and sedentary behaviour after stroke: Physical Activity Routines After Stroke (PARAS). METHODS: Adult stroke survivors and healthcare professionals were recruited from North East England stroke services. Stroke survivor physical activity and sedentary behaviour were targeted by a self-management behavioural intervention supported by healthcare professionals trained in intervention delivery. The main outcomes were protocol and intervention acceptability and feasibility and fidelity of intervention delivery. RESULTS: Eleven healthcare professionals (9 physiotherapists; 2 occupational therapists) participated in the study. Stroke survivor recruitment was lower than anticipated (19 versus target of up to 35). The healthcare professional training programme was feasible, with fidelity assessment of delivery supporting this finding. Data completeness was acceptable according to a priori criteria (>60%), except for stroke survivor questionnaire return rate (59%) and interview uptake (52%). No serious adverse events occurred. Healthcare professionals and stroke survivors perceived intervention delivery to be feasible and acceptable with minor modifications highlighted including the potential for earlier delivery in the stroke pathway. CONCLUSIONS: The study protocol and intervention delivery were feasible and acceptable to stroke survivors and healthcare professionals with modifications required before large-scale evaluation. TRIAL REGISTRATION: ISRCTN35516780 . Registered on October 24, 2018.

Using intervention mapping to develop and facilitate implementation of a multifaceted behavioural intervention targeting physical activity and sedentary behaviour in stroke survivors: Physical Activity Routines After Stroke (PARAS): intervention development study.

Objectives: The benefits of increased physical activity for stroke survivors include improved function and mental health and wellbeing. However, less than 30% achieve recommended physical activity levels, and high levels of sedentary behaviour are reported. We developed a multifaceted behavioural intervention (and accompanying implementation plan) targeting physical activity and sedentary behaviour of stroke survivors. Design: Intervention Mapping facilitated intervention development. Step 1 involved a systematic review, focus group discussions and a review of care pathways. Step 2 identified social cognitive determinants of behavioural change and behavioural outcomes. Step 3 linked determinants of behavioural outcomes with specific behaviour change techniques (BCTs) to target behaviours of interest. Step 4 involved intervention development informed by steps 1-3. Subsequently, an implementation plan was developed (Step 5) followed by an evaluation plan (Step 6). Setting: Community and secondary care settings, North East England. Participants: Stroke survivors and healthcare professionals (HCPs) working in stroke services. Results: Systematic review findings informed selection of nine 'promising' BCTs (e.g. problem-solving). Focus groups with stroke survivors (n = 18) and HCPs (n = 24) identified the need for an intervention delivered throughout the rehabilitation pathway, tailored to individual needs with training for HCPs delivering the intervention. Intervention delivery was considered feasible within local stroke services. The target behaviours for the intervention were levels of physical activity and sedentary behaviour in adult stroke survivors. Assessment of acceptability and usability with 11 HCPs and 21 stroke survivors/relatives identified issues with self-monitoring tools and the need for a physical activity repository of local services' and training for HCPs with feedback on intervention delivery. A feasibility study protocol was designed to evaluate the intervention. Conclusions: A systematic development process using intervention mapping resulted in a multi-faceted evidence- and theory-informed intervention (Physical Activity Routines After Stroke - PARAS) for delivery by community stroke rehabilitation teams.

Acceptability and deliverability of an auditory rhythmical cueing (ARC) training programme for use at home and outdoors to improve gait and physical activity post-stroke.

BACKGROUND: Although laboratory studies demonstrate that training programmes using auditory rhythmical cueing (ARC) may improve gait post-stroke, few studies have evaluated this intervention in the home and outdoors where deployment may be more appropriate. This manuscript reports stakeholder refinement of an ARC gait and balance training programme for use at home and outdoors, and a study which assessed acceptability and deliverability of this programme. METHODS: Programme design and content were refined during stakeholder workshops involving physiotherapists and stroke survivors. A two-group acceptability and deliverability study was then undertaken. Twelve patients post-stroke with a gait related mobility impairment received either the ARC gait and balance training programme or the gait and balance training programme without ARC. Programme provider written notes, participant exercise and fall diaries, adverse event monitoring and feedback questionnaires captured data about deliverability, safety and acceptability of the programmes. RESULTS: The training programme consisted of 18 sessions (six supervised, 12 self-managed) of exercises and ARC delivered by a low-cost commercially available metronome. All 12 participants completed the six supervised sessions and 10/12 completed the 12 self-managed sessions. Provider and participant session written records and feedback questionnaires confirmed programme deliverability and acceptability. CONCLUSION: An ARC gait and balance training programme refined by key stakeholders was feasible to deliver and acceptable to participants and providers. TRIAL REGISTRATION: ISCTRN 12/03/2018.

Auditory rhythmical cueing to improve gait and physical activity in community-dwelling stroke survivors (ACTIVATE): study protocol for a pilot randomised controlled trial.

BACKGROUND: Mobility problems are present in 70-80% of stroke survivors and can result in impaired gait and reduced physical activity limiting independent living. Auditory rhythmic cueing (ARC) has been used to provide auditory feedback and shows promise in improving a variety of walking parameters following stroke. The aim of this pilot study is to assess the feasibility of conducting a multi-centre, observer blind, randomised controlled trial of auditory rhythmical cueing (ARC) intervention in home and community settings in North East England. METHODS: This pilot observer blind randomised controlled feasibility trial aims to recruit 60 participants over 15 months from community stroke services in the North East of England. Participants will be within 24 months of stroke onset causing new problems with mobility. Each participant will be randomised to the study intervention or control group. Intervention treatment participants will undertake 18 auditory rhythmical cueing (ARC) treatment sessions over 6 weeks (3 × 30 min per week, 6 supervised (physiotherapist/research associate)/12 self-managed) in a home/community setting. A metronome will be used to provide ARC during a series of balance and gait exercises, which will be gradually progressed. The control treatment participants will undertake the same duration balance and gait exercise training programme as the intervention group but without the ARC. Feasibility will be determined in terms of recruitment, retention, adverse events, adherence, collection of descriptive clinical and accelerometer motor performance data at baseline, 6 weeks and 10 weeks and description of participant, provider and clinical therapists' experiences. As well as using questionnaires to collate participant views, qualitative interviews will be undertaken to further understand how the intervention is delivered in practice in a community setting and to identify aspects perceived important by participants. DISCUSSION: The ACTIVATE study will address an important gap in the evidence base by reporting whether it is feasible to deliver auditory rhythmical cueing in the home and community to improve gait and balance parameters following stroke. The feasibility of the study protocol will be established and results will inform the design of a future multi-centre randomised controlled trial. TRIAL REGISTRATION: Trial register: ISRCTN, Trial identifier: ISRCTN10874601: Date of registration: 12/03/2018.

A feasibility, acceptability and fidelity study of a multifaceted behaviour change intervention targeting free-living physical activity and sedentary behaviour in community dwelling adult stroke survivors.

BACKGROUND: Despite the benefits of physical activity for walking ability, balance, and mood, less than 30% of stroke survivors engage in recommended levels of physical activity with high levels of sedentary behaviour observed. This study aims to assess the feasibility, acceptability and fidelity of a theory- and evidence-based multifaceted behaviour change intervention targeting free-living physical activity and sedentary behaviour after stroke. METHODS: This study will be set in community stroke services in the North East of England and will assess the feasibility of a behaviour change intervention targeting free-living physical activity and sedentary behaviour of stroke survivors and consultation behaviour of the healthcare professionals to support stroke survivors to make these lifestyle changes. Up to 35 stroke survivors currently receiving stroke rehabilitation within the study catchment area with capacity and no contraindications to increasing physical activity/reducing sedentary behaviour will be recruited. Stroke survivors will receive a supported self-management physical activity/sedentary behaviour programme incorporating provision of information, goal setting, action planning, barrier identification, coping planning, self-monitoring and feedback on physical activity and sedentary behaviour. The programme will be supported by up to 12 healthcare professionals (HCPs) recruited from the community stroke services taking part in the study. The HCPs will deliver at least two face-to-face sessions (baseline, review and subsequent reviews if necessary) and provide a range of personalised tools to support each individual stroke survivor (e.g. workbook, self-monitoring tools, information on local resources). The consultation behaviour of the HCPs will be targeted via a training programme incorporating face-to-face training, a training manual and individual feedback on intervention programme delivery from the study research team. The feasibility, acceptability and fidelity of the study protocol will be assessed. DISCUSSION: The most effective methods of supporting stroke survivors to alter physical activity and sedentary behaviour have yet to be established. This study will establish the feasibility of delivering a complex theory- and evidence-based intervention targeting the behaviour of both stroke survivors and HCPs and assess whether it is acceptable to the target populations. Findings will inform the iterative development of the intervention before a larger scale evaluation. TRIAL REGISTRATION: Trial register: Trial identifier: ISRCTN35516780, date of registration: 24/10/2018.

Evaluation of an Extended Stroke Rehabilitation Service (EXTRAS): A Randomized Controlled Trial and Economic Analysis.

Background and Purpose- There is limited evidence to guide rehabilitation to meet the longer term needs of stroke survivors. The clinical effectiveness and cost-effectiveness of an extended stroke rehabilitation service (EXTRAS) provided following early supported discharge were determined. Methods- EXTRAS was a pragmatic parallel-group observer-blind randomized controlled trial involving 19 UK centers. Patients with stroke were individually randomized to receive EXTRAS or usual care at discharge from early supported discharge. Five EXTRAS reviews were provided by an early supported discharge team member between one and 18 months, usually by telephone. Reviews consisted of a semi-structured interview assessing progress, rehabilitation needs, and service provision, with goal setting and action planning. The primary outcome was performance in extended activities of daily living (Nottingham EADL Scale) at 24 months post-randomization. The Nottingham EADL Scale is scored 0 to 66, with higher scores indicating better performance in these activities. Cost-effectiveness was estimated using resource utilization costs and Quality Adjusted Life Years. Analyses were intention to treat. Results- Between January 9, 2013 and October 26, 2015, 573 participants were randomized (EXTRAS, n=285; usual care, n=288). Mean 24 month Nottingham EADL Scale scores were EXTRAS (n=219) 40.0 (SD 18.1) and usual care (n=231) 37.2 (SD 18.5) giving an adjusted mean difference of 1.8 (95% CI, -0.7 to 4.2). 1155/1338 (86%) of expected EXTRAS reviews were undertaken. Over 24 months, the mean cost of resource utilization was lower in the intervention group: -£311 (-$450 [95% CI, -£3292 to £2787; -$4764 to $4033]). EXTRAS provided more Quality Adjusted Life Years (0.07 [95% CI, 0.01 to 0.12]). At current conventional thresholds of willingness to pay (£20 000 [$28 940] per Quality Adjusted Life Years), there was a 90% chance that EXTRAS could be considered cost-effective. Conclusions- EXTRAS did not significantly improve stroke survivors' performance in extended activities of daily living. However, given the impact on costs and Quality Adjusted Life Years, EXTRAS may be an affordable addition to improve stroke care. Clinical Trial Registration- URL: www.isrctn.com. Unique identifier: ISRCTN45203373.

Botulinum Toxin for the Upper Limb after Stroke (BoTULS) Trial: effect on impairment, activity limitation, and pain.

BACKGROUND AND PURPOSE: Botulinum toxin is increasingly used to treat upper limb spasticity due to stroke, but its impact on arm function is unclear. We evaluated botulinum toxin for upper limb spasticity and function poststroke. METHODS: Three hundred thirty-three patients with stroke with upper limb spasticity and reduced arm function participated in a multicenter randomized controlled trial. The intervention group received botulinum toxin type A injection(s) plus a 4-week therapy program. The control group received the therapy program alone. Repeat injection(s) and therapy were available at 3, 6, and 9 months. The primary outcome was upper limb function at 1 month (Action Research Arm Test). Secondary outcomes included measures of impairment, activity limitation, and pain at 1, 3, and 12 months. Outcome assessments were blinded and analysis was by intention to treat. RESULTS: There was no significant difference in achievement of improved arm function (Action Research Arm Test) at 1 month (intervention group: 42 of 167 [25.1%], control group 30 of 154 [19.5%]; P=0.232). Significant differences in favor of the intervention group were seen in muscle tone at 1 month; upper limb strength at 3 months; basic arm functional tasks (hand hygiene, facilitation of dressing) at 1, 3, and 12 months; and pain at 12 months. CONCLUSIONS: Botulinum toxin type A is unlikely to be useful for improving active upper limb function (eg, reaching and grasping) in the majority of patients with spasticity after stroke, but it may improve basic upper limb tasks (hand hygiene, facilitation of dressing) and pain.

A biomechanical investigation into the validity of the modified Ashworth Scale as a measure of elbow spasticity.

OBJECTIVE: To investigate the criterion validity of the modified Ashworth Scale. POPULATION: Volunteers from a stroke population admitted to a district general hospital stroke unit diagnosed with a first ever stroke less than 26 weeks previously. OUTCOME MEASURES: Resistance to passive movement about the elbow was simultaneously quantified (biomechanically) and graded (modified Ashworth Scale). Passive range of movement and peak instantaneous velocity during passive movement were also measured. ANALYSIS: Criterion validity was investigated as convergent construct validity (using the Spearman's correlation coefficient) and concurrent validity (using analysis of variance). RESULTS: One hundred measurements were taken on 63 subjects. Correlation between the modified Ashworth Scale and resistance to passive movement was 0.511. Resistance to passive movement and velocity showed significant differences between the modified Ashworth score of '0' and a modified Ashworth score greater than '0' (p < 0.01). There were no significant differences between MAS '1', '1+' and '2'. Resistance to passive movement in the impaired arm was significantly higher than in the nonimpaired arm (p < 0.01). CONCLUSION: The modified Ashworth Scale does not provide a valid measure of spasticity at lower grades but it may provide a measure of resistance to passive movement.

Shoulder pain after stroke: a research challenge.

BACKGROUND: An evidence-based approach to the management of shoulder pain after stroke is required, but systematic reviews have highlighted the small number of studies suitable for use in developing clinical guidelines. DESIGN: This brief overview summarises obstacles to shoulder pain research that systematic reviews have identified, and compares their therapeutic recommendations to the Royal College of Physicians National Clinical Guidelines for Stroke. CONCLUSION: Clinicians treating shoulder pain after stroke can refer to guidelines and systematic reviews, but there are differences in their conclusions regarding the use of steroid injections and electrical stimulation. There is unanimous agreement that further efforts are required to examine interventions singly and in combination.