Is the difference real, is the difference relevant: the minimal detectable and clinically important changes in the Montreal Cognitive Assessment.

Background and aims: The Montreal Cognitive Assessment (MoCA) is a widely used instrument for assessing cognitive function in stroke survivors. To interpret changes in MoCA scores accurately, it is crucial to consider the minimal detectable change (MDC) and minimal clinically important difference (MCID). The aim was to establish the MDC and MCID of the MoCA within 6 months after stroke. Methods: This cohort study analysed data from the EFFECTS trial. The MoCA was administered at baseline and at 6-month follow-up. The MDC was calculated as the upper limit of the 95 % confidence interval of the standard error of the MoCA mean. The MCID was determined using anchor-based and distribution methods. The visual analogue recovery scale of the Stroke Impact Scale (SIS [primary anchor]) and Euro Quality of Life-5 Dimensions index (EQ-5D [confirmatory anchor]) were used as anchors. The distribution-based method, the Cohen benchmark effect size was chosen. Results: In total, 1131 (mean age [SD], 71 [10.6] years) participants were included. The mean (SD) MoCA scores at admission and 6-month follow-up were 22 (5.2) and 25 (4.2), respectively. The MDC of the MoCA was 5.1 points. The anchor method yielded the MCIDs 2 and 1.6 points for SIS and EQ-5D, respectively. Using the distribution method, the MCID for the MoCA was 1 point. Conclusions: Even a small change in MoCA scores can be important for stroke survivors; however, larger differences are required to ensure that any difference in MoCA values is a true change and is not related to the inherent variation in the test. Due to small sample sizes, the results of the anchor analysis need to be interpreted with caution.

Factors associated with changes in walking performance in individuals 3 months after stroke or TIA: secondary analyses from a randomised controlled trial of SMS-delivered training instructions in Sweden.

OBJECTIVES: This study aimed to identify factors related to changes in walking performance in individuals 3 months after a stroke or TIA. DESIGN: Cross-sectional study with post hoc analysis of a randomised controlled study. SETTING: University Hospital, Sweden. PARTICIPANTS: 79 individuals, 64 (10) years, 37% women, who were acutely hospitalised because of stroke or TIA between November 2016 and December 2018. Inclusion criteria were patients aged 18 or above and the major eligibility criterion was the ability to perform the 6 min walking test. INTERVENTION: The intervention group received standard care plus daily mobile phone text messages (short message service) with instructions to perform regular outdoor walking and functional leg exercises in combination with step counting and training diaries. The control group received standard care. OUTCOME MEASURES: Multivariate analysis was performed and age, sex, group allocation, comorbidity, baseline 6 min walk test, body mass index (BMI), cognition and chair-stand tests were entered as possible determinants for changes in the 6 min walk test. RESULTS: Multiple regression analyses showed that age (standardised beta -0.33, 95% CI -3.8 to -1.05, p<0.001), sex (-0.24, 95% CI -66.9 to -8.0, p=0.014), no comorbidity (-0.16, 95% CI -55.5 to 5.4, p=0.11), baseline BMI (-0.29, 95% CI -8.1 to -1.6, p=0.004), baseline 6 min walk test (-0.55, 95% CI -0.5 to -0.3, p<0.001) were associated with changes in 6 min walk test 3 months after the stroke event. The regression model described 36% of the variance in changes in the 6 min walk test. CONCLUSIONS: Post hoc regression analyses indicated that younger age, male sex, lower BMI and shorter 6 min walk test at baseline and possible no comorbidity contributed to improvement in walking performance at 3 months in patients with a recent stroke or TIA. These factors may be important when planning secondary prevention actions. TRIAL REGISTRATION NUMBER: NCT02902367.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

BACKGROUND: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. METHODS: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. FINDINGS: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. INTERPRETATION: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Cerebrovascular Hemodynamics in Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis of Transcranial Doppler Studies.

INTRODUCTION: Transcranial Doppler (TCD) sonography is a noninvasive tool for measuring cerebrovascular hemodynamics. Studies have reported alterations in cerebrovascular hemodynamics in normal aging, mild cognitive impairment (MCI), and dementia, as well as in different etiologies of dementia. This systematic review and meta-analysis was designed to investigate the relationship between cerebral blood velocity (CBv) and pulsatility index (PI) in the middle cerebral artery (MCA) in persons with MCI and dementia. METHODS: A systematic literature search was conducted in Pubmed, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL. The search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of 33,439 articles, 86 were reviewed in full-text, and 35 fulfilled the inclusion criteria. RESULTS: CBv was significantly lower and PI significantly higher in MCA in vascular dementia (VaD) and Alzheimer's disease (AD) compared to cognitively normal (CN) older persons. Also, CBv was lower in MCI compared to CN. There were no significant differences in CBv in MCA in AD compared with VaD, although PI was higher in VaD compared to AD. CONCLUSION: Alterations in cerebrovascular hemodynamics are seen in AD, VaD, and MCI. While PI was slightly higher in VaD compared to AD, the reduction in CBv appears to be equally pronounced across neurodegenerative and vascular etiologies of dementia.

Study protocol for a randomized, controlled, multicentre, pragmatic trial with Rehabkompassen®-a digital structured follow-up tool for facilitating patient-tailored rehabilitation in persons after stroke.

BACKGROUND: Stroke is a leading cause of disability among adults worldwide. A timely structured follow-up tool to identify patients' rehabilitation needs and develop patient-tailored rehabilitation regimens to decrease disability is largely lacking in current stroke care. The overall purpose of this study is to evaluate the effectiveness of a novel digital follow-up tool, Rehabkompassen®, among persons discharged from acute care settings after a stroke. METHODS: This multicentre, parallel, open-label, two-arm pragmatic randomized controlled trial with an allocation ratio of 1:1 will be conducted in Sweden. A total of 1106 adult stroke patients will have follow-up visits in usual care settings at 3 and 12 months after stroke onset. At the 3-month follow-up, participants will have a usual outpatient visit without (control group, n = 553) or with (intervention group, n = 553) the Rehabkompassen® tool. All participants will receive the intervention at the 12-month follow-up visit. Feedback from the end-users (patient and health care practitioners) will be collected after the visits. The primary outcomes will be the patients' independence and social participation at the 12-month visits. Secondary outcomes will include end-users' satisfaction, barriers and facilitators for adopting the instrument, other stroke impacts, health-related quality of life and the cost-effectiveness of the instrument, calculated by incremental cost per quality-adjusted life year (QALY). DISCUSSION: The outcomes of this trial will inform clinical practice and health care policy on the role of the Rehabkompassen® digital follow-up tool in the post-acute continuum of care after stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915027. Registered on 4 June 2021. ISRCTN registry ISRCTN63166587. Registered on 21 August 2023.

Development of a Swedish short version of the Montreal Cognitive Assessment for cognitive screening in patients with stroke.

OBJECTIVE: The primary objective was to develop a Swedish short version of the Montreal Cognitive Assessment (s-MoCA-SWE) for use  with patients with stroke. Secondary objectives were to identify an optimal cut-off value for the s-MoCA-SWE to screen for cognitive impairment and to compare its sensitivity with that of previously developed short forms of the Montreal Cognitive Assessment. DESIGN: Cross-sectional study. SUBJECTS/PATIENTS: Patients admitted to stroke and rehabilitation units in hospitals across Sweden. METHODS: Cognition was screened using the Montreal Cognitive Assessment. Working versions of the s-MoCA-SWE were developed using supervised and unsupervised algorithms. RESULTS: Data from 3,276 patients were analysed (40% female, mean age 71.5 years, 56% minor stroke at admission). The suggested s-MoCA-SWE comprised delayed recall, visuospatial/executive function, serial 7, fluency, and abstraction. The aggregated scores ranged from 0 to 16. A threshold for impaired cognition ≤ 12 had a sensitivity of 97.41 (95% confidence interval, 96.64-98.03) and positive predictive value of 90.30 (95% confidence interval 89.23-91.27). The s-MoCA-SWE had a higher absolute sensitivity than that of other short forms. CONCLUSION: The s-MoCA-SWE (threshold ≤ 12) can detect post-stroke cognitive issues. The high sensitivity makes it a potentially useful "rule-out" tool that may eliminate severe cognitive impairment in people with stoke.

Physical Activity Trajectories and Functional Recovery After Acute Stroke Among Adults in Sweden.

Importance: The optimum level and timing of poststroke physical activity interventions to enhance functional recovery remain unclear. Objective: To assess the level of physical activity in the first 6 months after stroke among individuals with similar physical activity patterns over time and to investigate the association between physical activity trajectories and functional recovery at 6 months after stroke. Design, Setting, and Participants: This cohort study obtained data from the Efficacy of Fluoxetine-a Randomized Controlled Trial in Stroke, which was conducted in 35 stroke and rehabilitation centers across Sweden from October 2014 to June 2019. Adult participants (aged >18 years) were recruited between 2 and 15 days after stroke onset and followed up for 6 months. Participants who withdrew or were lost to follow-up were excluded from the longitudinal analysis. Data analyses were performed between August 15 and October 28, 2022. Exposures: Physical activity was assessed at 1 week, 1 month, 3 months, and 6 months. Multiple factors associated with physical activity trajectories were investigated. Association of the distinct trajectories with functional recovery was assessed in multivariable logistic regression. Main Outcomes and Measures: The primary outcomes were the distinct physical activity trajectories over time, which were identified using group-based trajectory modeling. The secondary outcome was the functional recovery at 6 months after stroke, which was assessed using the modified Rankin Scale. Results: Of the 1367 included participants (median [IQR] age, 72 years [65-79] years; 844 males [62%]), 2 distinct trajectory groups were identified: increaser (n = 720 [53%]) and decreaser (647 [47%]). The increaser group demonstrated a significant increase in physical activity level (mean difference, 0.27; linear slope ß1 = 0.46; P < .001) and sustained it at light intensity from 1 week to 6 months, whereas the decreaser group showed a decline in physical activity and eventually became inactive (mean difference, -0.26; linear slope ß1 = 1.81; P < .001). Male participants and those with normal cognition had higher odds of being in the increaser group, regardless of stroke severity. Increasing physical activity and sustaining it at light intensity were associated with a good functional outcome at 6 months (adjusted odds ratio, 2.54; 99% CI, 1.72-3.75; P < .001). Conclusions ad Relevance: Results of this study suggest that increased physical activity was associated with functional recovery 6 months after stroke. Interventions targeting individuals with decreasing physical activity in the subacute phase of stroke may play a role in improved functional outcomes.

The impact of stroke on the ability to live an independent life at old age: a community-based cohort study of Swedish men.

INTRODUCTION: Few studies with controls from the same cohort have investigated the impact of stroke on the ability to live an independent life at old age. We aimed to analyze how great an impact being a stroke survivor would have on cognition and disability. We also analyzed the predictive value of baseline cardiovascular risk factors. METHODS: We included 1147 men, free from stroke, dementia, and disability, from the Uppsala Longitudinal Study of Adult Men, between 69-74 years of age. Follow-up data were collected between the ages of 85-89 years and were available for 481 of all 509 survivors. Data on stroke diagnosis were obtained through national registries. Dementia was diagnosed through a systematic review of medical charts and in accordance with the current diagnostic criteria. The primary outcome, preserved functions, was a composite outcome comprising four criteria: no dementia, independent in personal activities of daily living, ability to walk outside unassisted, and not living in an institution. RESULTS: Among 481 survivors with outcome data, 64 (13%) suffered a stroke during the follow-up. Only 31% of stroke cases, compared to 72% of non-stroke cases (adjusted OR 0.20 [95% CI 0.11-0.37]), had preserved functions. The chance of being free of dementia was 60% lower in the stroke group, OR 0.40 [95% CI 0.22-0.72]. No cardiovascular risk factors were independently able to predict preserved functions among stroke cases. CONCLUSION: Stroke has long lasting consequences for many aspects of disability at very high age.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Does fluoxetine reduce apathetic and depressive symptoms after stroke? An analysis of the Efficacy oF Fluoxetine-a randomized Controlled Trial in Stroke trial data set.

OBJECTIVE: Apathy is a common and disabling symptom after stroke with no proven treatments. Selective serotonin reuptake inhibitors are widely used to treat depressive symptoms post-stroke but whether they reduce apathetic symptoms is unknown. We determined the effect of fluoxetine on post-stroke apathy in a post hoc analysis of the EFFECTS (Efficacy oF Fluoxetine-a randomized Controlled Trial in Stroke) trial. METHODS: EFFECTS enrolled patients ⩾18 years between 2 and 15 days after stroke onset. Participants were randomly assigned to receive oral fluoxetine 20 mg once daily or matching placebo for 6 months. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and 6 months. Individual items on this scale were divided into those reflecting symptoms of apathy and depression. Symptoms were compared between fluoxetine and placebo groups. RESULTS: Of 1500 participants enrolled, complete MADRS data were available for 1369. The modified intention-to-treat population included 681 patients in the fluoxetine group and 688 in the placebo group. Confirmatory factor analysis revealed that apathetic, depressive, and anhedonic symptoms were dissociable. Apathy scores increased in both fluoxetine and placebo groups (both p ⩽ 0.00001). In contrast, fluoxetine was associated with a reduction in depressive scores (p = 0.002). CONCLUSION: Post-stroke apathetic and depressive symptoms respond differently to fluoxetine treatment. Our analysis suggests fluoxetine is ineffective in preventing post-stroke apathy.

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset. AIM: This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia) on magnetic resonance imaging (MRI) performed at stroke diagnosis. SUMMARY OF REVIEW: We searched the literature from inception to January 2022 and identified 10,284 records. We included studies that performed MRI at the time of stroke (0-30 days after a stroke) and assessed cognitive outcome at least 3 months after stroke. We synthesized findings from 26 papers, comprising 27 stroke-populations (N = 13,114, average age range = 40-80 years, 19-62% female). When data were available, we pooled unadjusted (ORu) and adjusted (ORa) odds ratios.We found associations between cognitive outcomes and presence of cerebral atrophy (three studies, N = 453, ORu = 2.48, 95% CI = 1.15-4.62), presence of microbleeds (two studies, N = 9151, ORa = 1.36, 95% CI = 1.08-1.70), and increasing severity of white matter hyperintensities (three studies, N = 704, ORa = 1.26, 95% CI = 1.06-1.49). Increasing cerebral small vessel disease score was associated with cognitive outcome following unadjusted analysis only (two studies, N = 499, ORu = 1.34, 95%CI = 1.12-1.61; three studies, N = 950, ORa = 1.23, 95% CI = 0.96-1.57). Associations remained after controlling for pre-stroke cognitive impairment. We did not find associations between other stroke features and cognitive outcome, or there were insufficient data. CONCLUSION: Acute stroke MRI features may enable healthcare professionals to identify patients at risk of post-stroke cognitive problems. However, there is still substantial uncertainty about the prognostic utility of acute MRI for this.

Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

Digital Graphic Follow-up Tool (Rehabkompassen) for Identifying Rehabilitation Needs Among People After Stroke: Randomized Clinical Feasibility Study.

BACKGROUND: Stroke is a leading cause of disability among adults, with heavy social and economic burden worldwide. A cost-effective solution is urgently needed to facilitate the identification of individual rehabilitation needs and thereby provide tailored rehabilitations to reduce disability among people who have had a stroke. A novel digital graphic follow-up tool Rehabkompassen has recently been developed to facilitate capturing the multidimensional rehabilitation needs of people who have had a stroke. OBJECTIVE: The aim of this study was to evaluate the feasibility and acceptability of conducting a definitive trial to evaluate Rehabkompassen as a digital follow-up tool among people who have had a stroke in outpatient clinical settings. METHODS: This pilot study of Rehabkompassen was a parallel, open-label, 2-arm prospective, proof-of-concept randomized controlled trial (RCT) with an allocation ratio of 1:1 in a single outpatient clinic. Patients who have had a stroke within the 3 previous months, aged ≥18 years, and living in the community were included. The trial compared usual outpatient visits with Rehabkompassen (intervention group) and without Rehabkompassen (control group) at the 3-month follow-up as well as usual outpatient visit with Rehabkompassen at the 12-month follow-up. Information on the recruitment rate, delivery, and uptake of Rehabkompassen; assessment and outcome measures completion rates; the frequency of withdrawals; the loss of follow-up; and satisfaction scores were obtained. The key outcomes were evaluated in both groups. RESULTS: In total, 28 patients (14 control, 14 Rehabkompassen) participated in this study, with 100 patients screened. The overall recruitment rate was 28% (28/100). Retention in the trial was 86% (24/28) at the 12-month follow-up. All participants used the tool as planned during their follow-ups, which provided a 100% (24/24) task completion rate of using Rehabkompassen and suggested excellent feasibility. Both patient- and physician-participants reported satisfaction with the instrument (19/24, 79% and 2/2, 100%, respectively). In all, 2 (N=2, 100%) physicians and 18 (N=24, 75%) patients were willing to use the tool in the future. Furthermore, modified Rankin Scale as the primary outcome and various stroke impacts as secondary outcomes were both successfully collected and compared in this study. CONCLUSIONS: This study demonstrated the high feasibility and adherence of the study protocol as well as the high acceptability of Rehabkompassen among patients who have had a stroke and physicians in an outpatient setting in comparison to the predefined criterion. The information collected in this feasibility study combined with the amendments of the study protocol may improve the future definitive RCT. The results of this trial support the feasibility and acceptability of conducting a large definitive RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915027; https://clinicaltrials.gov/ct2/show/NCT04915027.

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST).

BACKGROUND: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. OBJECTIVE: To publish the detailed statistical analysis plan for TWIST prior to unblinding. METHODS: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting. DISCUSSION: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Predicting post-stroke cognitive impairment using acute CT neuroimaging: A systematic review and meta-analysis.

BACKGROUND: Identifying whether acute stroke patients are at risk of cognitive decline could improve prognostic discussions and management. Structural computed tomography neuroimaging is routine in acute stroke, and may identify those at risk of post-stroke dementia or post-stroke cognitive impairment (PSCI). AIM: To systematically review the literature to identify which stroke or pre-stroke features on brain computed tomography scans, performed at the time of stroke, are associated with post-stroke dementia or PSCI. SUMMARY OF REVIEW: We searched electronic databases to December 2020. We included studies reporting acute stroke brain computed tomography, and later diagnosis of a cognitive syndrome. We created summary estimates of size of unadjusted association between computed tomography features and cognition. Of 9536 citations, 28 studies (41 papers) were eligible (N = 7078, mean age 59.8-78.6 years). Cognitive outcomes were post-stroke dementia (10 studies), PSCI (17 studies), and one study analyzed both. Fifteen studies (N = 2952) reported data suitable for meta-analyses. White matter lesions (WML) (six studies, N = 1054, OR = 2.46, 95% CI = 1.25-4.84), cerebral atrophy (four studies, N = 558, OR = 2.80, 95% CI = 1.21-6.51), and pre-existing stroke lesions (three studies, N = 352, OR = 2.38, 95% CI = 1.06-5.32) were associated with post-stroke dementia. WML (four studies, N = 473, OR = 3.46, 95% CI = 2.17-5.52) were associated with PSCI. Other computed tomography features were either not associated with cognitive outcome, or there were insufficient data. CONCLUSIONS: Cognitive impairment following stroke is of great concern to patients and carers. Features seen on visual assessment of acute stroke computed tomography brain scans are strongly associated with cognitive outcomes. Clinicians should consider when and how this information should be discussed with stroke survivors.

Complete functional recovery in a child after endovascular treatment of basilar artery occlusion caused by spontaneous dissection: a case report.

Stroke caused by dissection of arteries of the vertebrobasilar system in children is still poorly investigated in terms of etiology, means of treatment, course of disease, and prognosis. The aim of this report was to describe the unusual course of a spontaneous dissection of the basilar artery (BA) in a child treated with endovascular techniques and to point out that the plasticity of the brain stem can fully compensate for structural damage caused by stroke. We report the case of a 15-year-old boy who suffered a wake-up stroke with BA occlusion caused by spontaneous dissection. A blood clot was aspirated from the false lumen and the true lumen re-opened, but the patient deteriorated a few hours later, and repeated angiography revealed that the intimal flap was detached, occluding the BA again. The lumen of BA was then reconstructed by a stent. Despite a large pons infarction, the patient was completely recovered 11 months after the onset. The case was analyzed with angiograms and magnetic resonance imaging, macroscopic and microscopic pathological analysis, computed tomographic angiography, magnetic resonance-based angiography, and diffusion tensor imaging. This case illustrates that applied endovascular techniques and intensive care measures can alter the course of potentially fatal brain stem infarction. Our multimodal analysis gives new insight into the anatomical basis for the plasticity mechanism of the brain stem.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta-analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre-specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow-up. Thirty-eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD -0.0; 95% CI -0.05 to 0.05; 5 studies, 5436 participants, high-quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high-quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high-quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high-quality evidence). Cognition was slightly better in the control group (MD -1.22, 95% CI -2.37 to -0.07; 4 studies, 5373 participants, moderate-quality evidence). Only one study (n = 30) reported neurological deficit score (SMD -0.39, 95% CI -1.12 to 0.33; low-quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, -0.02 to 0.08; 6 studies, 5518 participants, moderate-quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high-quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate-quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high-quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD -0.06; 95% CI -1.24 to 1.11; 4 studies, 5524 participants, moderate-quality of evidence), nor in quality of life (MD 0.00; 95% CI -0.02 to 0.02, 3 studies, 5482 participants, high-quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta-analysis of outcomes at end of follow-up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

Potential effects on cardiometabolic risk factors and body composition by short message service (SMS)-guided training after recent minor stroke or transient ischaemic attack: post hoc analyses of the STROKEWALK randomised controlled trial.

OBJECTIVES: To evaluate effects of mobile phone text-messaging exercise instructions on body composition, cardiometabolic risk markers and self-reported health at 3 months after stroke. DESIGN: Randomised controlled intervention study with per-protocol analyses. SETTING: University Hospital in Sweden. PARTICIPANTS: Seventy-nine patients (mean (SD) age 64 (10) years, 37% female) ≥18 years with good motor function (modified Rankin Scale ≤2) and capable to perform 6 min walking test at hospital discharge were randomised to either intervention (n=40) or control group (n=39). Key exclusion criteria: subarachnoid bleeding, uncontrolled hypertension, severe psychiatric problems or cognitive limitations. INTERVENTIONS: The intervention group received beyond standard care, daily mobile phone instructional text messages to perform regular outdoor walking and functional leg exercises. The control group received standard care. MAIN OUTCOME MEASURES: Fat mass and fat-free mass were estimated by bioelectric impedance analysis. Cardiometabolic risk factors like blood lipids, glycated haemoglobin and blood glucose were analysed at baseline and after 3 months. RESULTS: Both groups changed favourably in fat-free mass (1.83 kg, 95% CI 0.77 to 2.89; p=0.01, effect size (ES)=0.63 vs 1.22 kg, 95% CI 0.39 to 2.0; p=0.05, ES=0.54) and fat mass (-1.30 kg, 95% CI -2.45 to -0.14; p=0.029, ES=0.41 vs -0.76 kg, 95% CI -1.74 to 0.22; p=0.123, ES=0.28). Also, many cholesterol related biomarkers improved; for example, total cholesterol -0.65 mmol/L, 95% CI -1.10 to -0.2; p=0.06, ES: 0.5 vs -1.1 mmol/L, 95% CI -1.47 to -0.56; p>0.001, ES=0.8. However, there were no between-group differences. At 3 months, 94% and 86%, respectively, reported very good/fairly good health in the text messaging and control groups. CONCLUSIONS: No clear effect of 3 months daily mobile phone delivered training instructions was detected on body composition, cardiovascular biochemical risk factors or self-perceived health. Further research is needed to evaluate secondary prevention efforts in larger populations after recent stroke. TRIAL REGISTRATION NUMBER: NCT02902367.

Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial.

Background and Purpose: The EFFECTS (Efficacy of Fluoxetine­a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. Methods: EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. Results: One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76­1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75­100) versus 93 (interquartile range, 82­100); P=0.0021 and communication 93 (interquartile range, 82­100) versus 96 (interquartile range, 86­100); P=0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. Conclusions: Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02683213.