Chronic Stroke Research Articles

Blood-brain barrier disruption following brain injury: Implications for clinical practice.

The blood-brain barrier (BBB) plays a critical role in regulating the exchange of substances between peripheral blood and the central nervous system and in maintaining the stability of the neurovascular unit in neurological diseases. To guide clinical treatment and basic research on BBB protection following brain injury, this manuscript reviews how BBB disruption develops and influences neural recovery after stroke and traumatic brain injury (TBI). By summarizing the pathological mechanisms of BBB damage, we underscore the critical role of promoting BBB repair in managing brain injury. We also emphasize the potential for personalized and precise therapeutic strategies and the need for continued research and innovation. From this, broadening insights into the mechanisms of BBB disruption and repair could pave the way for breakthroughs in the treatment of brain injury-related diseases.

Evaluating Biomarkers of Bone Health After an 8-Week Walking Program in Non-Ambulatory Stroke Survivors: A Pilot Study

Background/Objectives: Stroke survivors have a significantly increased likelihood of developing osteoporosis, a condition characterized by weak and brittle bones as well as an elevated risk of bone fractures. However, previous studies on exercise intervention have mostly been on stroke survivors who are able to walk. The objective of this study was to examine the effect of walking exercise on bone health in non-ambulatory stroke survivors. Methods: This pre- and post-test study enrolled a group of chronic non-ambulatory stroke survivors. They were instructed to complete an 8-week aerobic walking exercise program, three sessions per week. Serum concentrations of osteocalcin (OC) and carboxy-terminal telopeptides of type I collagen (ICTP) were evaluated at baseline and after completing the walking exercise program. In addition, we assessed the ambulation capacity and balance control using the functional ambulation category (FAC) and Berg Balance Scale (BBS), respectively. Results: A total of 9 out of 10 non-ambulatory stroke survivors who were recruited completed the intervention. The serum concentration of OC significantly increased from 8.51 ± 2.28 ng/mL to 9.39 ± 2.97 ng/mL (p < 0.10). The serum concentration of ICTP significantly increased from 4.45 ± 2.58 ng/mL to 5.31 ± 2.92 ng/mL (p < 0.10). Both FAC and BBS scores significantly improved from 1.0 ± 0 to 1.33 ± 0.5 (p < 0.1) and from 7.22 ± 10.02 to 15.78 ± 14.81 (p < 0.01), respectively. Conclusions: The findings of this pilot study suggest that walking exercise may improve bone health by initiating a bone remodeling process in chronic non-ambulatory stroke survivors.

Examining the effects of non-immersive virtual reality game-based training on knee hyperextension control and balance in chronic stroke patients: a single-blind randomized controlled study.

Post-stroke hemiparesis can lead to decreased mobility, gait disturbances, impaired balance, postural instability, limitations in activities of daily living (ADL), and long-term disability. The aim of this study was to examine the effect of non-immersive virtual reality game-based training (nIVRGT) in addition to conventional rehabilitation in stroke patients on dynamic balance, knee hyperextension control, and ADL. Twenty-five chronic stroke patients aged between 51 and 70 were included in the study. Stroke patients were randomized to a control group (n = 12) and a study group (n = 13). Individuals in control group participated conventional physiotherapy and rehabilitation program for 60min, 3 days a week for 6 weeks. individuals in the study group received 40min of conventional physiotherapy and rehabilitation program plus 20min nIVRGT. Functional Reach Test, Timed Up and Go Test, Computerized Gait Evaluation System and Barthel Index were used in the evaluation. The study group improved significantly in dynamic balance, knee control, and ADL (p < 0.05). In the control group, significant improvements were observed in dynamic balance and knee control (p < 0.05), except ADL (p > 0.05). The study group improved in dynamic balance compared with the control group (p < 0.05). Knee control and ADL improved similarly in both groups (p > 0.05). Our results showed that conventional and additional nIVRGT rehabilitation improved dynamic balance and knee hyperextension control in chronic stroke. However, it was observed that the non-immersive virtual reality (nIVR) approach was more effective in improving dynamic balance in stroke patients than conventional rehabilitation alone. NCT05907473.

Correction: Comparing the effects of Swiss-ball training and virtual reality training on balance, mobility, and cortical activation in individuals with chronic stroke: study protocol for a multi-center randomized controlled trial

Correction: Comparing the effects of Swiss-ball training and virtual reality training on balance, mobility, and cortical activation in individuals with chronic stroke: study protocol for a multi-center randomized controlled trial

Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men

Abstract Introduction Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%). Purpose to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes. Methods From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates. Results We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p&amp;lt;0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p&amp;lt;0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p&amp;lt;0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p&amp;lt;0.001) and emergency admissions (38.4% vs 25.7%, p&amp;lt;0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p&amp;lt;0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p&amp;lt;0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p&amp;lt;0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p&amp;lt;0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p&amp;lt;0.001]. Conclusion PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.

Heart rate and prognosis of heart failure with reduced ejection fraction in women and men in sinus rhythm

Abstract Background Resting heart rate (HR) is a well-established therapeutic target for treating heart failure (HF). Beta-blockers are the primary drugs to reduce HR. Elevated HR is associated with higher mortality in heart failure with reduced ejection fraction (HFrEF). However, the influence of HR on mortality and predictors of death in women with HFrEF in sinus rhythm is not well understood. Purpose to analyse mortality for HR ≤60&amp;gt;bpm and ≤70&amp;gt;bpm in women and men. Methods From February 2017 to January 2022, we analysed the influence of resting HR (≤60&amp;gt; and ≤70&amp;gt;bpm) on mortality and predictors of death in women and men with HFrEF in sinus rhythm. Baseline data included clinical characteristics and echocardiographic findings. The HR used in the analysis was obtained at the closest outpatient visit to the death event. We used the adjustment for multiple comparisons for the log-rank test of Kaplan-Meier (K-M) and Cox proportional hazards methods to analyse mortality rates and search for death predictors for women and men. Results We analysed 2,984 patients, with a mean age of 61 ± 13.8 years, 1,922 (64.4%) men. Age, body mass index, myocardial infarction, diabetes, chronic kidney disease, stroke, carvedilol dosage, hospitalization, and initial left ventricular ejection fraction (LVEF) were similar in both genders. Over the follow-up period of 3.7±1.6 years, we observed an increase in LVEF in men (29.5%±6.7% vs. 36.7%±12.9%; p&amp;lt;0.001) and women (29.9%±6.4 vs. 38.0%±13.4%; p&amp;lt;0.001), and HR reduced in men (73.1±13.0 to 72.1±11.8 bpm; p=0.007) and women (72.8±12.7 to 71.8±11.3 bpm; p=0.026). Death incidence was higher in men (43.7% vs. 36.7%; p&amp;lt;0.001). The cumulative incidence of death was higher in men with HR&amp;gt;60bpm (K-M: log-rank p&amp;lt;0.001) and &amp;gt;70bpm (K-M: log-rank p=0.011) compared to women. Cox regression for death, adjusted for covariates with p&amp;lt;0.25, showed age (HR=1.01;95%CL:1.008-1.017; p&amp;lt;0.001), men (HR=0.80;95%CL:0.71-0.90; p&amp;lt;0.001), LVEF (HR=0.986;95%CL:0.98-0.99; p=0.001), and HR (HR=1.005;95%CL:1.00-1.01; p=0.025) as independent death variables. For men, the independent variables were age (HR=1.01;95%CL:1.01-1.02; p=0.002), LVEF (HR=0.98;95%CL:0.97-0.99; p=0.001), and HR (HR=1.008;95%CL:1.00-1.01; p=0.008), and for women, only the age (HR=1.02;95%CL:1.01-1.02; p&amp;lt;0.001). Conclusion Increased HR was an independent variable of death in men but not in women. Future studies are needed to determine the best reference HR for a chronotropic drug intervention to reduce mortality in women with HFrEF in sinus rhythm.

Impact of atrial fibrillation on cardiac autonomic function in elderly patients

Abstract Introduction Cardiac autonomic dysfunction has been linked to an increased risk of mortality (1), stroke and silent brain lesions (2) and cognitive impairment (3) in patients with atrial fibrillation (AF). However, the impact of AF on cardiac autonomic function is poorly understood. Purpose We aimed to explore the impact of AF on cardiac autonomic function by comparing AF patients with a matched control cohort without AF. Methods We enrolled patients with and without AF from two ongoing, prospective, multicenter cohort studies (Swiss-AF Cohort and Swiss-AF Control) if they had a high-resolution 16-lead resting ECG recording in sinus rhythm for a duration of 5 minutes at baseline visit. Cardiac autonomic function was quantified by periodic repolarization dynamics (PRD), a marker of repolarization instability associated with sympathetic activity. PRD was quantified by means of wavelet analysis, as validated previously (4). Cardiac autonomic dysfunction was defined present if PRD exceeded the established cut-off of 10.0 deg2 (5). We built multivariable adjusted linear and logistic regression models to explore the association of AF with PRD and cardiac autonomic dysfunction. Results We included 2077 patients, 1113 (54%) from the AF cohort and 964 (46%) from the matched non-AF cohort. Baseline characteristics were well balanced between the groups (mean age 71 vs. 73 years in patients with and without AF, mean CHA2DS2-VASc score 3.0 vs. 3.5, female sex 31.3% vs. 36.6%). The median PRD was 18.2 deg2 (IQR 9.9-25.4) in patients with AF and 15.8 deg2 (IQR 8.1 -23.0) in patients without AF (p&amp;lt;0.001, Figure). 832 (75%) of the AF patients suffered from cardiac autonomic dysfunction, vs. 656 (68%) of the non-AF patients (p&amp;lt;0.001). Multivariable adjusted linear regression analysis revealed an independent association of AF with continuous levels of PRD (beta-coefficient -1.57, 95% CI -2.64 - -0.488, p=0.004). Further, AF was independently associated with the presence of cardiac autonomic dysfunction (Odds Ratio 1.48, 95% CI 1.18-1.87, p&amp;lt;0.001, Table). Conclusion In this cross-sectional analysis of a patient population with and without AF, AF was independently associated with increased PRD values, reflecting sympathetic predominance, and with the presence of cardiac autonomic dysfunction. These findings implicate a relevant role of AF in the development of cardiac autonomic dysfunction in elderly patients.Figure

Echocardiographic signs of atrial cardiopathy and MRI-detected silent brain infarcts in a middle-aged cohort: the Akershus Cardiac Examination 1950 Study

Abstract Background Atrial fibrillation (AF) is linked to clinical stroke and silent brain infarction (SBI). In the majority of AF patients, there exists a recognized form of atrial cardiopathy, and it is suggested that atrial cardiopathy, even in the absence of AF, may serve as a risk factor for stroke. However, existing evidence is limited, and it remains unclear whether atrial cardiopathy indeed poses a risk for stroke and SBI. Purpose We aimed to investigate the association between echocardiographic signs of atrial cardiopathy and the detection of SBI through magnetic resonance imaging (MRI) in a middle-aged cohort from the general population. Methods In the prospective Akershus Cardiac Examination (ACE) 1950 Study conducted within the general population in Norway, cardiovascular risk assessment including transthoracic echocardiography, was undertaken at study inclusion between 2012 and 2015. We assessed body surface area-indexed left atrial (LA) maximum and minimum volume, as well as LA reservoir and contractile strain. Subsequently, brain MRI was conducted in a subset of the cohort between 2017 and 2023. SBI was defined as presence of neuroimaging sign of infarcts, including lacunes, in individuals without a history of stroke. Logistic regression analyses were performed to explore the associations between echocardiographic measures of atrial cardiopathy and SBI on MRI, adjusting for sex, age, hypertension, and diabetes. Results A total of 397 out of 3706 (10.7%) participants in the ACE 1950 study underwent MRI examination and were included in this analysis. At the time of MRI, the mean age was 70.0±2.2 years, with 157 (40%) women, 248 (62%) with hypertension, and 36 (9%) with diabetes at study inclusion. SBI was present in 51 (13%), of which only 1 (2%) had known AF. After excluding 18 participants with pre-existing AF, no significant difference were observed in LA volumes or LA strain between participants with or without SBI (Figure 1). In unadjusted and adjusted logistic regression analyses, neither LA volume nor LA strain were associated with SBI (Table 1). Conclusion Echocardiographic signs of atrial cardiopathy were not associated with silent brain infarcts in a middle-aged cohort from the general population.

Neutrophil-Mimetic Upconversion Photosynthetic Nanosystem Derived from Microalgae for Targeted Treatment of Thromboembolic Stroke.

Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.

Effect of integrated manual and verbal cueing on functional transfers in chronic stroke survivors: a randomized controlled study

Purpose The profession of physical therapy has historically relied on manual facilitation to improve motor control strategies and performance in persons rehabilitating from a stroke, yet there is insufficient evidence to support its use during functional task training. The purpose of this study was to determine the effects of integrated cueing (verbal and manual) and verbal cueing approaches during sit-to-stand training on midline alignment & muscle activation in chronic stroke survivors. Methods Twenty-one chronic right-brained stroke survivors with hemiplegia were randomly assigned to the Integrated Cueing or Verbal Only group and outcome measures were recorded using an 18-Camera Motion Capture System, force plates, and surface electromyography (EMG). Results Both groups demonstrated a significant improvement in symmetry toward the midline after thirty training repetitions. Significant improvements in muscle activation were found in two muscle groups on the affected side of the body in the Integrated Cueing group, gastrocnemius and rectus femoris. Conclusion Both the Verbal Only and Integrated Cueing groups made significant progress toward more symmetrical movement, yet more significant changes in the activation of hemiparetic extensor muscles were seen in the Integrated Cueing group. These findings support the use of manual cueing in movement activation and performance during the training of functional tasks. IMPLICATIONS FOR REHAB Physical therapists commonly use manual tactile cues to facilitate movement performance but there is currently insufficient evidence to support this use with stroke survivors. In a relatively small sample size, both verbal cues and integrated cues (verbal plus manual) improved symmetry during sit to stand in chronic right brain stroke survivors. Integrated cueing enhanced motor activation and performance during sit to stand better than verbal cues alone. Manual tactile cueing should be considered during functional task retraining.

First-in-Human Phase I Clinical Trial of the Adenosine A1R/A3R Agonist AST-004 in Healthy Subjects.

AST-004 is a small-molecule adenosine A1/A3 receptor agonist that has exhibited significant cerebroprotective efficacy in preclinical models of acute ischemic stroke and traumatic brain injury. The primary objectives of this clinical phase I first-in-human study were to evaluate the safety and tolerability profile of single ascending intravenous doses in healthy subjects. The secondary objectives were to characterize the single-dose pharmacokinetic profiles in plasma, cerebrospinal fluid (CSF), and urine. In part 1 of the study, AST-004 was administered in ascending dose cohorts of 5, 25, 50, 75, and 100 mg, with 6 subjects in each cohort receiving the study drug and 2 receiving placebo. In part 2, all 12 subjects received a 100 mg IV infusion of the study drug followed by a single CSF collection per subject via lumbar puncture at 20, 40, or 60 minutes after infusion. A total of 42 subjects received AST-004, with no severe or serious adverse events observed. Twelve of these subjects experienced a treatment-emergent adverse event, the most frequent across groups being headache. In part 2, pharmacokinetic analyses confirmed that AST-004 was distributed in the CSF, with the CSF-to-plasma ratio increasing over the 3 timepoints sampled. The mean half-life was 1.1 to 1.4 hours for doses of 25 to 100 mg, and the geometric mean maximum plasma concentration obtained in the highest dosing cohort (100 mg) was 2232±428 ng/mL. AST-004 was safe and well-tolerated at plasma concentrations 3 to 8× higher than those associated with significant efficacy in astrocyte's preclinical primate stroke efficacy studies, with CSF concentrations highest at the 60-minute collection timepoint, the last timepoint tested. This study supports additional clinical investigations, including evaluation of an extended infusion to support the phase 2 program in stroke and traumatic brain injury.

Effects of muscle strength exercise on muscle mass and muscle strength in patients with stroke: a systematic review and meta-analysis

This study systematically reviews the effects of muscle strength exercises on muscle mass and strength in stroke patients by analyzing randomized controlled trials. Ten studies, involving a total of 378 stroke patients, were included in the meta-analysis. The standardized mean difference (SMD) and confidence intervals (CIs) were calculated using a random effects model. The results indicated that strength exercises had a medium effect on increasing muscle strength in stroke patients (SMD, 0.6; 95% CI, 0.47–0.72; &lt;i&gt;I&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 51%; &lt;i&gt;P&lt;/i&gt;&lt; 0.05). Specifically, strength exercises were found to be particularly effective in chronic stroke patients, showing a medium effect on muscle strength (SMD, 0.68; 95% CI, 0.55–0.81; &lt;i&gt;I&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 45%; &lt;i&gt;P&lt;/i&gt;&lt; 0.05). The study also compared the effects based on repetition maximum (RM) settings, revealing that strength increased significantly regardless of whether RM was used, with studies showing medium effects (with RM: SMD, 0.52; 95% CI, 0.4–0.64; &lt;i&gt;I&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 0%; &lt;i&gt;P&lt;/i&gt;&lt; 0.05; without RM: SMD, 0.65; 95% CI, 0.4–0.91; &lt;i&gt;I&lt;sup&gt;2&lt;/sup&gt;&lt;/i&gt; = 72%; &lt;i&gt;P&lt;/i&gt;&lt; 0.05). The study concludes that strength exercises are beneficial for improving muscle strength in chronic stroke patients, but the use of RM to set exercise intensity is not strictly necessary.

Relationship between locus of control and health-related quality of life in chronic stroke patients: a cross-sectional study

IntroductionStroke is a major cause of disability in adults and the elderly worldwide. Post-stroke rehabilitation success largely depends on consistent participation in treatment sessions and adherence to prescribed physical exercises; however, factors such as individual belief about their health status often affect motivation, slowing recovery. Addressing these influences is essential for improving health-related quality of life and optimizing recovery outcomes.MethodsThis study employed a cross-sectional and correlational design with convenience sampling. The aim was to explore the relationship between recovery locus of control (RLOC) and health-related quality of life (HRQoL) among chronic stroke survivors. The Recovery Locus of Control scale and the EuroQol 5D-5L scale were utilized for assessment.ResultsA total of 69 participants were included in this survey. The mean RLOC score was 34.91, with internal RLOC at 21.16 and external RLOC at 13.77 and the total EQ5D index was 0.659. Age was a significant grouping factor, with the 30–39 age group showing a significant positive relationship (r = 1.000, p = 0.002), pain and anxiety/depression (p = .045), mobility and anxiety/depression (p = .009), anxiety/depression and self-care (p = .047), IRLOC and ERLOC (p = .013).ConclusionThe study found that while respondents exhibited high RLOC scores, there was no significant relationship between RLOC scores and the EQ5D-5L index score, suggesting that other factors may play a more critical role in influencing HRQoL among chronic stroke survivors.

Screening cutoff values to identify the risk of falls after stroke: A scoping review.

The present scoping review aimed to summarize and determine the accuracy of the variables and cutoff values reported to date for identifying fall risk in patients with stroke and identify the commonalities, limitations, and clinical implications. Articles published by the end of 2023 were searched using PubMed, Cumulative Index of Nursing and Allied Health Literature, and Scopus electronic databases. Two reviewers created a search formula, searched the databases, and conducted primary and secondary screenings. This review included 21 articles. The most commonly used individual indicator for identifying fall risk after stroke was the Berg Balance Scale; the cutoff values were relatively consistent, ranging between 46.5 and 50.5 points (area under the curve: 0.72-0.81). For the Timed Up and Go test and Falls Efficacy Scale-International, the cutoff values were in the range of 15-19 s and 27-29 points, respectively, and were relatively consistent across the articles. However, the area under the curve values were low (0.66-0.70 and 0.68-0.71, respectively). Among various assessments, the Berg Balance Scale is the most extensively studied tool, with established cutoff values associated with falls risk. It serves as a reliable indicator for detecting fall risk, especially in community-dwelling individuals with chronic stroke.

Feasibility of a 10-week community-based mobile health rehabilitation program using the WalkWithMe application in late sub-acute and chronic stroke survivors in a low resource setting: A pilot study

ABSTRACT Physical functioning can be increased in people with stroke by using a mobile health application. This study aimed to investigate the feasibility of a 10-week community-based program using the WalkWithMe (WWM) application in people with late sub-acute and chronic stroke in Benin. An interventional pilot study with mixed methods research design was used examining the application of an unsupervised individualized mobile Health (mHealth) instructed training program. Main outcome included the application usage, safety, adherence, perceived enjoyment, mHealth quality, patient experiences and pre-post efficacy measures. Nine adults, five males, median age of 60 years and time since stroke of 12 months participated in this study. For most participants adherence with the application was over 70%. However, some usability problems were observed due to incorrect understanding and use by participants and technical problems. The application was very fun, stimulating and enjoyable. Significant improvements were found with median (pre/post measures) of locomotors skill (1.4/3.4); impairments (38/40), Barthel Index (85/95), activity limitation (2.1/3.1), and quality of life (194/218). A trend towards significant improvement was found with 6 minutes walking test (181/220, p = 0.06). The WWM application is perceived as a potential approach to increase physical activity and functioning among people with stroke in Benin.

Video Game-Based Trunk Exercises for Rehabilitation in Chronic Stroke Survivors: A Mixed-Methods Feasibility Study

Video Game-Based Trunk Exercises for Rehabilitation in Chronic Stroke Survivors: A Mixed-Methods Feasibility Study

Circulating Blood-Brain Barrier Proteins for Differentiating Ischaemic Stroke Patients from Stroke Mimics

Background: Stroke is one of the leading causes of death and disability worldwide. The diagnosis of stroke remains largely clinical, yet widely used stroke scoring systems and brain imaging do not satisfactorily allow the distinction of ischaemic stroke (IS) patients from stroke mimics (SMs). Blood biomarkers are promising tools that could facilitate clinical triage. Methods: This study recruited 66 patients with IS and 24 SMs. The levels of Glial fibrillary acidic protein (GFAP), Neuron-specific enolase (NSE), Neurofilament light chain (NfL) and blood-brain barrier (BBB) proteins [Occludin (OCLN), Zonula occludens 1 (ZO-1), Claudin-5] in blood serum were measured by enzyme-linked immunosorbent assay technique. Biomarker levels in IS patients and SMs were compared using the Mann–Whitney U test. Multivariable logistic regression analysis was used to evaluate the diagnostic performance of biomarkers in combination with the National Institutes of Health Stroke Scale (NIHSS) score. Results: More significant differences in circulating GFAP, NfL, OCLN, ZO-1, and Claudin-5 but not NSE were found in IS patients compared to SMs. A combination of circulating ZO-1, Claudin-5, and OCLN with NIHSS score gives the highest diagnostic accuracy, sensitivity, and specificity. Conclusions: A prediction model with circulating BBB proteins in combination with NIHSS score differentiates between IS patients and SMs.

Lysosomal Ca2+ release-facilitated TFEB nuclear translocation alleviates ischemic brain injury by attenuating autophagic/lysosomal dysfunction in neurons

Neuronal death was frequently driven by autophagic/lysosomal dysfunction after ischemic stroke, whereas how to restore the impaired autophagic flux remained elusive. Autophagic/lysosomal signaling could be augmented after transcription factor EB (TFEB) nuclear translocation, which was facilitated by its dephosphorylation. A key TFEB dephosphorylase was calcineurin (CaN), whose activity was drastically regulated by cytosolic calcium ion concentration ([Ca2+]) controlled by lysosomal Ca2+ channel-like protein of TRPML1. Our research shows that ML-SA1, an agonist of the TRPML1 channel, significantly enhanced the lysosomal Ca2+ release and the CaN expression in penumbric neurons, subsequently promoted TFEB nuclear translocation, and greatly reversed autophagy/lysosome dysfunction. Moreover, ML-SA1 treatment significantly reduced neuronal loss, infarct size, and neurological deficits. By contrast, ML-SI3, an inhibitor of TRPML1, inhibited the lysosomal Ca2+ release conversely, aggravated the impairment of autophagic flux and consequentially exacerbated brain stroke lesion. These studies suggest that TRPML1 elevation alleviates ischemic brain injury by restoring autophagic/lysosomal dysfunction via Lysosomal Ca2+ release-facilitated TFEB nuclear translocation in neurons.

Post-stroke fatigue severity is associated with executive dysfunction in chronic stroke

ABSTRACT Following stroke, fatigue is highly prevalent and managing fatigue is consistently rated a key unmet need by stroke survivors and professionals. Domain-specific cognitive impairments have been associated with greater fatigue severity in earlier stages of stroke recovery, but it is unclear whether these associations hold in chronic (>2 years) stroke. The present cross-sectional observational study evaluates the relationship between domain-specific cognitive functioning and the severity of self-reported fatigue among chronic stroke survivors. Participants (N = 105; mean age = 72.92, 41.90% female; mean years post-stroke = 4.57) were assessed in domains of attention (Hearts Cancellation test), language (Boston Naming Test), episodic memory (Logical Memory Test), working memory (Digit Span Backwards task), and executive functioning (set-shifting: Trail Making Test, Part B), as part of the OX-CHRONIC study, a longitudinal stroke cohort. Fatigue was assessed using the Fatigue Severity Scale. In a multiple linear regression analysis inclusive of above cognitive domains, only poorer executive functioning was associated with increased fatigue severity. This provides insight into the cognitive impairment profile of post-stroke fatigue long-term after stroke, with executive functioning deficits as the key hallmark.

Measuring Exercise Self-Efficacy After Stroke: Validity and Reliability of Current Measures.

Many physically capable stroke survivors are insufficiently active, with low self-efficacy considered an important contributor. However, validity and reliability of self-efficacy measures in stroke survivors have not been established. This research aims to evaluate the test-retest reliability and construct validity of 3 self-efficacy measures: Self-Efficacy for Exercise Scale (SEE), Spinal Cord Injury Exercise Self-Efficacy Scale (SCI-ESES), and Participation Strategies Self-Efficacy Scale (PS-SES). A repeated measures study with community-dwelling, independently mobile adult stroke survivors (n=51, mean age 74years, 45% female, median 22months poststroke) was completed. Test-retest reliability was assessed using intraclass correlation coefficients and Bland-Altman analyses. Construct validity was assessed using 8 pre-determined hypotheses concerning physical activity level (subjective and objective), comorbidities, work and volunteering, and measures of function. Retest reliability was established for the SEE (intraclass correlation coefficient, ICC=0.77) and PS-SES (ICC=0.78) but not for the SCI-ESES (ICC=0.68). Bland-Altman analysis showed participants consistently scored higher on the second test for all measures. The SEE achieved construct validity by meeting 75% of hypotheses, whereas the PS-SES and SCI-ESES did not. Self-efficacy was positively related to steps/day, functional capacity, self-reported activity levels, and work or volunteering participation. The SEE was found to be the most appropriate tool to measure exercise self-efficacy in independently mobile chronic stroke survivors in terms of retest reliability and validity. N/A. for more insights from the authors (see the Video, Supplemental Digital Content 1 "Espernberger-JNPT-Video-Abstract," available at: http://links.lww.com/JNPT/A489).