Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

Background and Purpose: Optimizing speech and language therapy (SLT) regimens for maximal aphasia recovery is a clinical research priority. We examined associations between SLT intensity (hours/week), dosage (total hours), frequency (days/week), duration (weeks), delivery (face to face, computer supported, individual tailoring, and home practice), content, and language outcomes for people with aphasia. Methods: Databases including MEDLINE and Embase were searched (inception to September 2015). Published, unpublished, and emerging trials including SLT and ≥10 individual participant data on aphasia, language outcomes, and time post-onset were selected. Patient-level data on stroke, language, SLT, and trial risk of bias were independently extracted. Outcome measurement scores were standardized. A statistical inferencing, one-stage, random effects, network meta-analysis approach filtered individual participant data into an optimal model examining SLT regimen for overall language, auditory comprehension, naming, and functional communication pre-post intervention gains, adjusting for a priori–defined covariates (age, sex, time poststroke, and baseline aphasia severity), reporting estimates of mean change scores (95% CI). Results: Data from 959 individual participant data (25 trials) were included. Greatest gains in overall language and comprehension were associated with >20 to 50 hours SLT dosage (18.37 [10.58–26.16] Western Aphasia Battery–Aphasia Quotient; 5.23 [1.51–8.95] Aachen Aphasia Test–Token Test). Greatest clinical overall language, functional communication, and comprehension gains were associated with 2 to 4 and 9+ SLT hours/week. Greatest clinical gains were associated with frequent SLT for overall language, functional communication (3–5+ days/week), and comprehension (4–5 days/week). Evidence of comprehension gains was absent for SLT ≤20 hours, <3 hours/week, and ≤3 days/week. Mixed receptive-expressive therapy, functionally tailored, with prescribed home practice was associated with the greatest overall gains. Relative variance was <30%. Risk of trial bias was low to moderate; low for meta-biases. Conclusions: Greatest language recovery was associated with frequent, functionally tailored, receptive-expressive SLT, with prescribed home practice at a greater intensity and duration than reports of usual clinical services internationally. These exploratory findings suggest critical therapeutic ranges, informing hypothesis-testing trials and tailoring of clinical services. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42018110947.

Background: Previous studies suggested that enlarged perivascular spaces are neuroimaging markers of cerebral small vessel disease. However, it is not clear whether enlarged perivascular spaces are associated with cognitive impairment. We aimed to determine the cross-sectional relationship between enlarged perivascular spaces and small vessel disease, and to investigate the relationship between enlarged perivascular spaces and subsequent cognitive impairment in patients with recent cerebral ischemic event. Methods: Anonymized data were accessed from the virtual international stroke trial archive. We rated number of lacunes, white matter hyperintensities, brain atrophy, and enlarged perivascular spaces with validated scales on magnetic resonance brain images after the index stroke. We defined cognitive impairment as a mini mental state examination score of ≤26, recorded at one year post stroke. We examined the associations between enlarged perivascular spaces and clinical and imaging markers of small vessel disease at presentation and clinical evidence of cognitive impairment at one year using linear and logistic regression models. Results: We analyzed data on 430 patients with mean (±SD) age 64.7 (±12.7) years, 276 (64%) males. In linear regression analysis, age (β = 0.24; p < 0.001), hypertension (β = 0.09; p = 0.025), and deep white matter hyperintensities (β = 0.31; p < 0.001) were associated with enlarged perivascular spaces. In logistic regression analysis, basal ganglia enlarged perivascular spaces were independently associated with cognitive impairment at one year after adjusting for clinical confounders (OR = 1.72, 95% CI = 1.22–2.42) and for clinical and imaging confounders (OR = 1.54; 95% CI = 1.03–2.31). Conclusions: Our data show that in patients with ischemic cerebral events, enlarged perivascular spaces are cross-sectionally associated with age, hypertension, and white matter hyperintensities and suggest that enlarged perivascular spaces in the basal ganglia are associated with cognitive impairment after one year.

Background and Purpose— High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods— Analyses included 1722 patients in hyperacute trials (recruitment <8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results— Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions— High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.