Modulation of the Association Between Corticospinal Tract Damage and Outcome After Stroke by White Matter Hyperintensities.

BACKGROUND AND OBJECTIVES: Motor outcomes after stroke relate to corticospinal tract (CST) damage. The brain leverages surviving neural pathways to compensate for CST damage and mediate motor recovery. Thus, concurrent age-related damage from white matter hyperintensities (WMHs) might affect neurologic capacity for recovery after CST injury. The role of WMHs in post-stroke motor outcomes is unclear. In this study, we evaluated whether WMHs modulate the relationship between CST damage and post-stroke motor outcomes. METHODS: We used data from the multisite ENIGMA Stroke Recovery Working Group with T1 and T2/fluid-attenuated inversion recovery imaging. CST damage was indexed with weighted CST lesion load (CST-LL). WMH volumes were extracted with Freesurfer's SAMSEG. Mixed-effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment, controlling for age, days after stroke, and stroke volume. RESULTS: A total of 223 individuals were included. WMH volume related to motor impairment above and beyond CST-LL (ß = 0.178, 95% CI 0.025-0.331, p = 0.022). Relationships varied by WMH severity (mild vs moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (ß = 0.888, 95% CI 0.604-1.172, p < 0.001) with a CST-LL × WMH interaction (ß = -0.211, 95% CI -0.340 to -0.026, p = 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (ß = 0.299, 95% CI 0.008-0.590, p = 0.044), but did not significantly relate to CST-LL or a CST-LL × WMH interaction. DISCUSSION: WMHs relate to motor outcomes after stroke and modify relationships between motor impairment and CST damage. WMH-related damage may be under-recognized in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.

Prevalence of Arm Weakness, Pre-Stroke Outcomes and Other Post-Stroke Impairments Using Routinely Collected Clinical Data on an Acute Stroke Unit.

INTRODUCTION: The prevalence of upper limb motor weakness early post-stroke may be changing, which can have clinical and research implications. Our primary aim was to describe the prevalence of upper limb motor weakness early post-stroke, with a secondary aim to contextualize this prevalence by describing pre-stroke outcomes, other post-stroke impairments, functional activities, and discharge destination. METHODS: This cross-sectional observational study extracted clinical data from confirmed stroke patients admitted to a metropolitan stroke unit over 15-months. The primary upper limb weakness measure was Shoulder Abduction and Finger Extension (SAFE) score. Demographics (eg, age), clinical characteristics (eg, stroke severity), pre-stroke outcomes (eg, clinical frailty), other post-stroke impairments (eg, command following), functional activities (eg, ambulation), and discharge destination were also extracted. RESULTS: A total of 463 participants had a confirmed stroke and SAFE score. One-third of patients received ≥1 acute medical intervention(s). Nearly one-quarter of patients were classified as frail pre-stroke. Upper limb weakness (SAFE≤8) was present in 35% [95% CI: 30%-39%] at a median of 1-day post-stroke, with 22% presenting with mild-moderate weakness (SAFE5-8). The most common other impairments were upper limb coordination (46%), delayed recall (41%), and upper limb sensation (26%). After a median 3-day acute stroke stay, 52% of the sample were discharged home. CONCLUSION: Upper limb weakness was present in just over a third (35%) of the sample early post-stroke. Data on pre-stroke outcomes and the prevalence of other post-stroke impairments highlights the complexity and heterogeneity of stroke recovery. Further research is required to tease out meaningful recovery phenotypes and their implications.

Perseverance with home-based upper limb practice after stroke: perspectives of stroke survivors and their significant others.

PURPOSE: The aim of this study was to explore factors that influence stroke survivors' ability to persevere with home-based upper limb practice. METHODS: A qualitative descriptive study embedded within a theoretical framework was conducted. Data were collected through semi-structured focus group, dyadic, and individual interviews. The Theoretical Domains Framework and Capability, Opportunity, Motivation - Behaviour (COM-B) model guided data collection and directed content analysis. FINDINGS: Participants were 31 adult stroke survivors with upper limb impairment, with 13 significant other/s, who were living at home in Queensland, Australia. Three central tenants aligned with the COM-B and six themes were identified. Stroke survivors' capability to persevere was influenced by being physically able to practice and being able to understand, monitor and modify practice, their opportunity to persevere was influenced by accessing therapy and equipment required for practice and fitting practice into everyday life, and their motivation to persevere was influenced by having goals and experiencing meaningful outcomes and having support and being accountable. CONCLUSION: Persevering with practice is multifaceted for stroke survivors. All facets need to be addressed in the design of strategies to enhance stroke survivors' ability to persevere and in turn, enhance their potential for continued upper limb recovery.IMPLICATIONS FOR REHABILITATIONMany stroke survivors do not persevere with long-term home-based upper limb practice despite the belief that high dose practice will promote continued recovery.Therapists need to support stroke survivors to setup individualised goal-based home programs that they can complete independently, or with support, within their everyday life.Stroke survivors need coaching to monitor and modify their practice and map their progress, so that they can recognise and experience meaningful recovery.To optimise upper limb recovery after stroke, strategies to enhance stroke survivors' capability, opportunity, and motivation to persevere across the continuum of recovery, need to be co-designed by stroke survivors, therapists and researchers.

Control intervention design for preclinical and clinical trials: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.

Control intervention design for preclinical and clinical trials: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

Control comparator selection is a critical trial design issue. Preclinical and clinical investigators who are doing trials of stroke recovery and rehabilitation interventions must carefully consider the appropriateness and relevance of their chosen control comparator as the benefit of an experimental intervention is established relative to a comparator. Establishing a strong rationale for a selected comparator improves the integrity of the trial and validity of its findings. This Stroke Recovery and Rehabilitation Roundtable (SRRR) taskforce used a graph theory voting system to rank the importance and ease of addressing challenges during control comparator design. "Identifying appropriate type of control" was ranked easy to address and very important, "variability in usual care" was ranked hard to address and of low importance, and "understanding the content of the control and how it differs from the experimental intervention" was ranked very important but not easy to address. The CONtrol DeSIGN (CONSIGN) decision support tool was developed to address the identified challenges and enhance comparator selection, description, and reporting. CONSIGN is a web-based tool inclusive of seven steps that guide the user through control comparator design. The tool was refined through multiple rounds of pilot testing that included more than 130 people working in neurorehabilitation research. Four hypothetical exemplar trials, which span preclinical, mood, aphasia, and motor recovery, demonstrate how the tool can be applied in practice. Six consensus recommendations are defined that span research domains, professional disciplines, and international borders.

White matter hyperintensities modify relationships between corticospinal tract damage and motor outcomes after stroke.

Motor outcomes after stroke relate to corticospinal tract (CST) damage. Concurrent damage from white matter hyperintensities (WMHs) might impact neurological capacity for recovery after CST injury. Here, we evaluated if WMHs modulate the relationship between CST damage and post-stroke motor impairment outcome. We included 223 individuals from the ENIGMA Stroke Recovery Working Group. CST damage was indexed with weighted CST lesion load (CST-LL). Mixed effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment. WMH volume related to motor impairment above and beyond CST-LL (ß = 0.178, p = 0.022). We tested if relationships varied by WMH severity (mild vs. moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (ß = 0.888, p < 0.001) with a CST-LL x WMH interaction (ß = -0.211, 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (ß = 0.299, p = 0.044), but did not significantly relate to CST-LL or a CST-LL x WMH interaction. WMH-related damage may be under-recognised in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.

Stroke survivors' perspectives on decision-making about rehabilitation and the prospect of taking recovery-promoting drugs: A qualitative study.

Objectives: To investigate factors which influence stroke survivors' decision-making about their rehabilitation and the prospect of taking recovery-promoting drugs, to enhance their recovery. Methods: Seventeen stroke survivors who had undertaken stroke rehabilitation, and three spouses, participated in focus groups and individual interviews in northern Queensland, Australia. Inductive thematic analysis of the interview data was conducted in accordance with Braun and Clarke's six-phase process. Results: Two specific, pivotal decision points during participants' stroke recovery process were identified: 1) overall, when deciding what rehabilitation they would undertake and hypothetically what recovery-promoting drugs they would take, and 2) on a daily basis, when deciding whether to participate in rehabilitation and take recovery-promoting drugs on any given day. Six themes which described factors influencing their decision-making were: 'My options for rehabilitation and recovery-promoting drugs'; 'The costs of rehabilitation and recovery-promoting drugs'; 'My recovery goals'; 'What I can deal with today'; 'The people my rehabilitation and recovery-promoting drugs affect'; and 'Fitting rehabilitation and recovery-promoting drugs into my life.' These themes were applicable at either one or both of the identified decision points. Conclusion: Factors that influence stroke survivors' decision-making, overall and on a day-to-day basis, need to be considered to ensure they can make the best decisions for themselves to achieve their full recovery potential. Understanding the conditions under which a stroke survivor would take a recovery-promoting drug will contribute to the development of dosing protocols to which stroke survivors could adhere.

Dose, Content, and Context of Usual Care in Stroke Upper Limb Motor Interventions: A Systematic Review.

OBJECTIVE: The objectives of this systematic review were to describe the current dose and content of usual care upper limb motor intervention for inpatients following stroke and examine if context factors alter dose and content. DATA SOURCES: A systematic search (EMBASE, MEDLINE) was completed from January 2015 to February 2023 (PROSPERO CRD42021281986). METHODS: Studies were eligible if they reported non-protocolised usual care upper limb motor intervention dose data for stroke inpatients. Studies were rated using the Johanna Briggs Institute critical appraisal tool. Data were descriptively reported for dose dimensions of time (on task or, in therapy) and intensity (repetitions, repetition/minute), content (intervention type/mode), and context (e.g., severity strata). RESULTS: Eight studies were included from four countries, largely reflecting inpatient rehabilitation. Time in therapy ranged from 23 to 121 min/day. Time on task ranged from 8 to 44 min/day. Repetitions ranged from 36 to 57/session, and 15 to 282/day. Time on task was lowest in the stratum of people with severe upper limb impairment (8 min/day), the upper limit for this stratum was 41.5 min/day. There was minimal reporting of usual care content across all studies. CONCLUSION: Upper limb motor intervention dose appears to be increasing in usual care compared to prior reports (e.g., average 21 min/day and 23 to 32 repetitions/session). Context variability suggests that doses are lowest in the stratum of patients with a severely impaired upper limb. Consistent reporting of the multiple dimensions of dose and content is necessary to better understand usual care offered during inpatient rehabilitation.

Self-reported sleep disturbances among people who have had a stroke: a cross-sectional analysis.

BACKGROUND: Sleep disturbances and their potential association with stroke remains understudied at a population level. We sought to determine the prevalence of sleep disturbances among people who have effects of stroke compared with the general population. METHODS: We used data from people aged 18 years or older who responded to the sleep and chronic disease modules of the 2017-2018 cycle of the Canadian Community Health Survey (CCHS). We measured sleep disturbances by self-reports of having trouble staying awake most or all of the time; either short (< 5 h) or long (> 9 h) nightly sleep duration; having trouble going to or staying asleep most or all of the time; and never, rarely or sometimes having refreshing sleep. We used log-binomial and multinomial regression to investigate prevalence of sleep disturbances among respondents who reported effects of stroke compared with others, adjusting for confounding factors. RESULTS: We included 46 404 CCHS respondents, 682 of whom reported effects of stroke. The prevalence of sleep disturbances for those with effects of stroke was higher than among others in the sample with regard to trouble staying awake (13.0% v. 6.1%; adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.59-2.94), short or long duration sleep (28.9% v. 10.0%; adjusted RR 1.93, 95% CI 1.57-2.38), trouble going to or staying asleep, (28.1% v. 17.6%; adjusted RR 1.53, 95% CI 1.28-1.83) and lack of refreshing sleep (41.1% v. 37.1%; adjusted RR 1.30, 95% CI 1.14-1.49). The prevalence of at least 1 reported measure of sleep disturbance was 61.6% among those with effects of stroke, compared with 48.2% among others (adjusted RR 1.28, 95% CI 1.18-1.40). INTERPRETATION: Self-report of having effects of stroke was associated with increased prevalence of sleep disturbances compared with the general population. Sleep disturbances were reported by a high proportion of respondents with effects of stroke, indicating the importance of screening for related disorders.

Examining Dose Frameworks to Improve Aphasia Rehabilitation Research.

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research-the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions.

Responsiveness and trajectory of changes in the rating of everyday arm-use in the community and home (REACH) scale over the first-year post-stroke.

OBJECTIVE: To examine the trajectory of the Rating of Everyday Arm-use in the Community and Home (REACH) scores over the first-year post-stroke, determine if REACH scores are modified by baseline impairment level and explore the responsiveness of the REACH scale through hypothesis testing. DESIGN: Consecutive sample longitudinal study. SETTING: Participants were recruited from an acute stroke unit and followed up at three, six, and 12 months post-stroke. PARTICIPANTS: Seventy-three participants with upper limb weakness (Shoulder Abduction and Finger Extension score ≤ 8). MAIN MEASURES: The REACH scale is a six-level self-report classification scale that captures how the affected upper limb is being used in one's own environment. The Fugl-Meyer Upper Limb Assessment (FMA-UL), Stroke Upper Limb Capacity Scale (SULCS), accelerometer-based activity count ratio and Global Rating of Change Scale (GRCS) were used to capture upper limb impairment, capacity, and use. RESULTS: The following proportions of participants improved at least one REACH level: 64% from baseline to three months, 37% from three to six months and 13% from six to 12 months post-stroke. The trajectory of REACH scores over time was associated with baseline impairment. Change in REACH had a moderate correlation to change in SULCS and the GRCS but not FMA-UL or the activity count ratio. CONCLUSIONS: Results of hypothesis testing provide preliminary evidence of the responsiveness of the REACH scale. On average, individuals with severe impairment continued to show improvement in use over the first year, while those with mild/moderate impairment plateaued and a small proportion decreased in the early chronic phase.

Enhancing generalizability of stroke clinical trial results: Illustrations from upper-limb motor recovery trials.

INTRODUCTION: Broadening eligibility criteria has been a focus to increase the generalizability of trial findings. Using upper-limb motor trials conducted early post-stroke as the illustrative domain, we sought to (1) investigate whether the published aim and conclusion statements adequately reflect the generalizability of findings and (2) explore internal validity and feasibility as constraints to achieving generalizability. METHODS: We systematically applied a conceptual model of a trial sampling process to published literature from systematic review and prospective cross-sectional data. The eligibility criteria reported and used to exclude patients were classified by consensus as related to safety, internal validity, feasibility, or a combination thereof. Categorical data were reported as counts/proportions, and continuous data were reported as median (interquartile range (IQR)). RESULTS: Thirty trials (n = 1638 participants) were included in the published literature and 1013 patients in the prospective data set. Thirty-seven percent of trials did not describe their target population in the aim and conclusion, and 80% did not report all trial screening data. Eligibility criteria related to internal validity were the most common type reported and applied to exclude patients across both data sets. In the prospective data set, 70% of patients were excluded for more than one reason. CONCLUSION: Key information to support the generalizability of trial findings was insufficiently reported in published upper-limb motor research conducted early post-stroke. Broadening eligibility criteria alone is unlikely to sufficiently improve trial inclusivity due to internal validity constraints. Trials could achieve inclusivity through targeting multiple sub-populations, that in combination, produce clinically relevant results that are applicable to a broader population.

Upper-Limb Motor Intervention Elements That Drive Improvement in Biomarkers and Clinical Measures Post-Stroke: A Systematic Review in a Systems Paradigm.

OBJECTIVE: To use a systems paradigm to examine upper limb (UL) motor intervention elements driving biomarker and clinical measure improvement after stroke. METHODS: Databases were searched up to March 2022. Eligibility screening was completed by 2 authors. Studies using biomarkers and clinical measures pre- and post-upper limb intervention were included. Studies of adjunct interventions (eg, brain stimulation) were excluded. Cochrane Risk-of-Bias tools and Template for Intervention Description and Replication were used to rate studies. Studies were synthesized using a systems paradigm: intervention outcome was considered an emergent property of the systemic interactions of 4 intervention elements (demographics, type, quality, and dose) characterized by individual dimensions. RESULTS: Sixty-four studies (n = 1814 participants) containing 106 intervention groups (66 experimental; 40 control) were included. Combined biomarker and clinical outcomes defined 3 scenarios: restitution, mixed, and unchanged. The restitution scenario included more moderate-to-severely impaired participants in earlier recovery phases (<6 months). Interventions with graded difficulty were more frequently used in the restitution scenario compared with the unchanged scenario. No difference in quality or amount of therapy was identified when examining scenarios that demonstrated restitution compared to those that did not (mixed and unchanged). CONCLUSIONS: A systems paradigm may be one of many approaches to understand UL motor restitution. This review found no single element consistently delivered improvements in biomarkers and clinical measures in the examined intervention groups. Complex patterns formed by multiple interacting intervention elements were observed in participants with and without restitution.

Large dynamic range, high resolution optical heterodyne readout for high velocity slip events.

We present a free-space optical displacement sensor for measuring geological slip event displacements within a laboratory setting. This sensor utilizes a fiberized Mach-Zehnder based optical heterodyne system coupled with a digital phase lock loop, providing a large dynamic range (multiple centimeters), high displacement resolution (with an amplitude spectral density of <10-10 m/Hz for frequencies above 100 Hz), and high velocity tracking capabilities (up to 4.96 m/s). This displacement sensor is used to increase the displacement and the time sensitivity for measuring laboratory-scale earthquakes induced in geological samples by using a triaxial compression apparatus. The sensor architecture provides an improved displacement and time resolution for the millisecond-duration slip events, at high containment and loading pressure and high temperatures. Alternatively, the sensor implementation can be used for other non-contact displacement readouts that required high velocity tracking with low noise and large dynamic range sensing. We use 13 high-velocity slip events in Fontainebleau sandstone to show the large dynamic range displacement tracking ability and displacement amplitude spectral densities to demonstrate the optical readout's unique sensing capabilities.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.