Recovery In Chronic Stroke Research Articles

Evidence of aberrant anti-epstein-barr virus antibody response, though no viral reactivation, in people with post-stroke fatigue

BackgroundFatigue is a common complication of stroke that has a significant impact on quality of life. The biological mechanisms that underly post-stroke fatigue are currently unclear, however, reactivation of latent viruses and their impact on systemic immune function have been increasingly reported in other conditions where fatigue is a predominant symptom. Epstein-Barr virus (EBV) in particular has been associated with fatigue, including in long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome, but has not yet been explored within the context of stroke.AimsWe performed an exploratory analysis to determine if there is evidence of a relationship between EBV reactivation and post-stroke fatigue.MethodsIn a chronic ischemic stroke cohort (> 5 months post-stroke), we assayed circulating EBV by qPCR and measured the titres of anti-EBV antibodies by ELISA in patients with high fatigue (FACIT-F < 40) and low fatigue (FACIT-F > 41). Statistical analysis between two-groups were performed by t-test when normally distributed according to the Shapiro-Wilk test, by Mann-Whitney test when the data was not normally distributed, and by Fisher’s exact test for categorical data.ResultsWe observed a similar incidence of viral reactivation between people with low versus high levels of post-stroke fatigue (5 of 22 participants (24%) versus 6 of 22 participants (27%)). Although the amount of circulating EBV was similar, we observed an altered circulating anti-EBV antibody profile in participants with high fatigue, with reduced IgM against the Viral Capsid Antigen (2.244 ± 0.926 vs. 3.334 ± 2.68; P = 0.031). Total IgM levels were not different between groups indicating this effect was specific to anti-EBV antibodies (3.23 × 105 ± 4.44 × 104 high fatigue versus 4.60 × 105 ± 9.28 × 104 low fatigue; P = 0.288).ConclusionsThese data indicate that EBV is not more prone to reactivation during chronic stroke recovery in those with post-stroke fatigue. However, the dysregulated antibody response to EBV may be suggestive of viral reactivation at an earlier stage after stroke.

Functional connectivity interacts with visual perceptual learning for visual field recovery in chronic stroke

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.

Use of a Foot-Induced Digitally Controlled Resistance Device for Functional Magnetic Resonance Imaging Evaluation in Patients with Foot Paresis.

Neurological deficits from a stroke can result in long-term motor disabilities, including those that affect walking gait. However, extensive rehabilitation following stroke is typically time limited. Establishing predictive biomarkers to identify patients who may meaningfully benefit from additional physical therapy and demonstrate improvement is important to improve the patients' quality of life. Detection of neuroplastic remodeling of the affected region and changes in the activity patterns excited while performing suitable motor tasks could have valuable implications for chronic stroke recovery. This protocol describes the use of a digitally controlled, magnetic resonance-compatible foot-induced robotic device (MR_COFID) to present a personalized foot-motor task involving trajectory following to stroke-affected subjects with gait impairment during functional magnetic resonance imaging (fMRI). In the task, foot flexion is performed against bi-directional resistive forces, which are tuned to the subject's strength in both the dorsiflexion and plantar flexion directions, while following a visual metronome. fMRI non-invasively uses endogenous deoxyhemoglobin as a contrast agent to detect blood oxygenation level-dependent (BOLD) changes between the active and resting periods during testing. Repeated periodic testing can detect therapy-related changes in excitation patterns during task performance. The use of this technique provides data to identify and measure biomarkers that may indicate the likelihood of an individual benefitting from rehabilitation beyond that which is currently provided to stroke patients.

Transcranial Direct Current Stimulation for Chronic Stroke: Is Neuroimaging the Answer to the Next Leap Forward?

During rehabilitation, a large proportion of stroke patients either plateau or begin to lose motor skills. By priming the motor system, transcranial direct current stimulation (tDCS) is a promising clinical adjunct that could augment the gains acquired during therapy sessions. However, the extent to which patients show improvements following tDCS is highly variable. This variability may be due to heterogeneity in regions of cortical infarct, descending motor tract injury, and/or connectivity changes, all factors that require neuroimaging for precise quantification and that affect the actual amount and location of current delivery. If the relationship between these factors and tDCS efficacy were clarified, recovery from stroke using tDCS might be become more predictable. This review provides a comprehensive summary and timeline of the development of tDCS for stroke from the viewpoint of neuroimaging. Both animal and human studies that have explored detailed aspects of anatomy, connectivity, and brain activation dynamics relevant to tDCS are discussed. Selected computational works are also included to demonstrate how sophisticated strategies for reducing variable effects of tDCS, including electric field modeling, are moving the field ever closer towards the goal of personalizing tDCS for each individual. Finally, larger and more comprehensive randomized controlled trials involving tDCS for chronic stroke recovery are underway that likely will shed light on how specific tDCS parameters, such as dose, affect stroke outcomes. The success of these collective efforts will determine whether tDCS for chronic stroke gains regulatory approval and becomes clinical practice in the future.

Neurovascular coupling is preserved in chronic stroke recovery after targeted photothrombosis

Functional neuroimaging, which measures hemodynamic responses to brain activity, has great potential for monitoring recovery in stroke patients and guiding rehabilitation during recovery. However, hemodynamic responses after stroke are almost always altered relative to responses in healthy subjects and it is still unclear if these alterations reflect the underlying brain physiology or if the alterations are purely due to vascular injury. In other words, we do not know the effect of stroke on neurovascular coupling and are therefore limited in our ability to use functional neuroimaging to accurately interpret stroke pathophysiology. To address this challenge, we simultaneously captured neural activity, through fluorescence calcium imaging, and hemodynamics, through intrinsic optical signal imaging, during longitudinal stroke recovery. Our data suggest that neurovascular coupling was preserved in the chronic phase of recovery (2 weeks and 4 weeks post-stoke) and resembled pre-stroke neurovascular coupling. This indicates that functional neuroimaging faithfully represents the underlying neural activity in chronic stroke. Further, neurovascular coupling in the sub-acute phase of stroke recovery was predictive of long-term behavioral outcomes. Stroke also resulted in increases in global brain oscillations, which showed distinct patterns between neural activity and hemodynamics. Increased neural excitability in the contralesional hemisphere was associated with increased contralesional intrahemispheric connectivity. Additionally, sub-acute increases in hemodynamic oscillations were associated with improved sensorimotor outcomes. Collectively, these results support the use of hemodynamic measures of brain activity post-stroke for predicting functional and behavioral outcomes.

May Dual Transcranial Direct Current Stimulation Enhance the Efficacy of Robot-Assisted Therapy for Promoting Upper Limb Recovery in Chronic Stroke?

Objective To assess whether dual transcranial direct current stimulation (tDCS) may enhance the efficacy of exoskeleton robotic training on upper limb motor functions in patients with chronic stroke. Methods A prospective, bi-center, double-blind, randomized clinical trial study was performed. Patients with moderate-to-severe stroke (according to The National Institute of Health Stroke Scale) were randomly assigned to receive dual or sham tDCS immediately before robotic therapy (10 sessions, 2 weeks). The primary outcome was the Fugl–Meyer for Upper Extremity, assessed before, after, and at the 12-week follow-up. Neurophysiological evaluation of corticospinal projections to upper limb muscles was performed by recording motor evoked potentials (MEPs). ClinicalTrials.gov-NCT03026712. Results Two hundred and sixty individuals were tested for eligibility, of which 80 were enrolled and agreed to participate. Excluding 14 dropouts, 66 patients were randomly assigned into the 2 groups. Results showed that chronic patients were stable before treatment and significantly improved after that. The records within subject improvements were not significantly different between the 2 groups. However, a post-hoc analysis subdividing patients in 2 subgroups based on the presence or absence of MEPs at the baseline showed a significantly higher effect of real tDCS in patients without MEPs when compared to patients with MEPs (F = 4.6, P = .007). Conclusion The adjunction of dual tDCS to robotic arm training did not further enhance recovery in the treated sample of patients with chronic stroke. However, a significant improvement in the subgroup of patients with a severe corticospinal dysfunction (as suggested by the absence of MEPs) suggests that they could benefit from such a treatment combination.

Oscillatory beta/alpha band modulations: A potential biomarker of functional language and motor recovery in chronic stroke?

Stroke remains one of the leading causes of various disabilities, including debilitating motor and language impairments. Though various treatments exist, post-stroke impairments frequently become chronic, dramatically reducing daily life quality, and requiring specific rehabilitation. A critical goal of chronic stroke rehabilitation is to induce, usually through behavioral training, experience-dependent plasticity processes in order to promote functional recovery. However, the efficiency of such interventions is typically modest, and very little is known regarding the neural dynamics underpinning recovery processes and possible biomarkers of their efficiency. Some studies have emphasized specific alterations of excitatory–inhibitory balance within distributed neural networks as an important recovery correlate. Neural processes sensitive to these alterations, such as task-dependent oscillatory activity in beta as well as alpha bands, may be candidate biomarkers of chronic stroke functional recovery. In this review, we discuss the results of studies on motor and language recovery with a focus on oscillatory processes centered around the beta band and their modulations during functional recovery in chronic stroke. The discussion is based on a framework where task-dependent modulations of beta and alpha oscillatory activity, generated by the deep cortical excitatory–inhibitory microcircuits, serve as a neural mechanism of domain-general top-down control processes. We discuss the findings, their limitations, and possible directions for future research.

Assessing the Sustainability of an Integrated Rural Sanitation and Hygiene Approach: A Repeated Cross-Sectional Evaluation in 10 Countries.

While many studies have implemented programs to increase sanitation coverage throughout the world, there are limited rigorous studies on the sustainability of these sanitation programs. Between 2014 and 2018, the rural Sustainable Sanitation and Hygiene for All (SSH4A) approach was implemented by SNV in sub-Saharan Africa and Asia. Repeated cross-sectional household surveys were administered annually throughout program implementation and 1 to 2 years following completion of program activities. We characterize to what extent sanitation coverage was sustained 1 to 2 years after implementation of this SSH4A intervention. Surveys were conducted in 12 program areas in 10 countries, with 22,666 households receiving a post-implementation survey. Six of 12 program areas (Bhutan, Ghana, Kenya, both Nepal sites, Tanzania) had similar coverage levels of basic sanitation 1-2 years post-implementation, whereas there were varying levels of slippage in the other program areas (both Ethiopia sites, Indonesia, Mozambique, Uganda, Zambia), ranging from a drop of 63 percentage points in coverage in Ethiopia to a drop of only 4 percentage points in Indonesia. In countries that experienced losses in the coverage of household sanitation, sanitation sharing among neighbors generally did not increase, whereas open defecation did increase. In each of the areas where slippage occurred, the sanitation coverage levels at the final time point were all still higher than the initial time point before SNV started working in these areas. We found several factors to be associated with the sustainability of sanitation coverage, including household socioeconomic status, having household members with disabilities, baseline sanitation coverage levels of the program areas, and rate of change of coverage during program activities. Data revealed sustained gains in sanitation coverage in some program areas, yet slippage in other areas. This work may serve to benchmark the sustainability of sanitation interventions in sub-Saharan Africa and Asia.

Clozapine-Induced Chemogenetic Neuromodulation Rescues Post-Stroke Deficits After Chronic Capsular Infarct

Long-term disabilities induced by stroke impose a heavy burden on patients, families, caregivers, and public health systems. Extensive studies have demonstrated the therapeutic value of neuromodulation in enhancing post-stroke recovery. Among them, chemogenetic neuromodulation activated by clozapine-N-oxide (CNO) has been proposed as the potential tool of neuromodulation. However, recent evidence showed that CNO does not cross the blood − brain barrier and may in fact have low binding affinity for chemogenetic tool. Thus, clozapine (CLZ) has been suggested for use in chemogenetic neuromodulation, in place of CNO, because it readily crosses the blood–brain barrier. Previously we reported that low doses of CLZ (0.1 mg/kg) successfully induced neural responses without off-target effects. Here, we show that low-dose clozapine (0.1 mg/kg) can induce prolonged chemogenetic activation while avoiding permeability issues and minimizing off-target effects. In addition, clozapine-induced excitatory chemogenetic neuromodulation (CLZ-ChemoNM) of sensory-parietal cortex with hsyn-hM3Dq-YFP-enhanced motor recovery in a chronic capsular infarct model of stroke in rats, improving post-stroke behavioral scores to 56% of pre-infarct levels. Longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET (FDG-microPET) scans showed that a reduction in diaschisis volume and activation of corticostriatal circuits were both correlated with post-stroke recovery. We also found c-Fos increases in bilateral cortices and BDNF increases in the cortices and striatum after CLZ-ChemoNM, indicating an increase in neural plasticity. These findings suggest the translational feasibility of CLZ-ChemoNM for augmenting recovery in chronic stroke.

Theta-gamma coupling as a cortical biomarker of brain-computer interface-mediated motor recovery in chronic stroke.

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain–computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain–computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain–computer interface. This study investigated whether the motor improvements in chronic stroke patients induced with a brain–computer interface therapy are associated with alterations in phase–amplitude coupling, a type of cross-frequency coupling. Seventeen chronic hemiparetic stroke patients used a robotic hand orthosis controlled with contralesional motor cortical signals measured with EEG. Patients regularly performed a therapeutic brain–computer interface task for 12 weeks. Resting-state EEG recordings and motor function data were acquired before initiating brain–computer interface therapy and once every 4 weeks after the therapy. Changes in phase–amplitude coupling values were assessed and correlated with motor function improvements. To establish whether coupling between two different frequency bands was more functionally important than either of those rhythms alone, we calculated power spectra as well. We found that theta–gamma coupling was enhanced bilaterally at the motor areas and showed significant correlations across brain–computer interface therapy sessions. Importantly, an increase in theta–gamma coupling positively correlated with motor recovery over the course of rehabilitation. The sources of theta–gamma coupling increase following brain–computer interface therapy were mostly located in the hand regions of the primary motor cortex on the left and right cerebral hemispheres. Beta–gamma coupling decreased bilaterally at the frontal areas following the therapy, but these effects did not correlate with motor recovery. Alpha–gamma coupling was not altered by brain–computer interface therapy. Power spectra did not change significantly over the course of the brain–computer interface therapy. The significant functional improvement in chronic stroke patients induced by brain–computer interface therapy was strongly correlated with increased theta–gamma coupling in bihemispheric motor regions. These findings support the notion that specific cross-frequency coupling dynamics in the brain likely play a mechanistic role in mediating motor recovery in the chronic phase of stroke recovery.

Neurovascular Coupling is Preserved in Chronic Stroke Recovery After Targeted Photothrombosis

Neurovascular Coupling is Preserved in Chronic Stroke Recovery After Targeted Photothrombosis

Rehabilitasi Latihan Fisik terhadap Pemulihan Pasca Stroke

This study aims to identify the effect of exercise and physical activity on post-stroke recovery. The method in this study is a literature review by collecting international databases, namely PubMed, Proquest, Science Direct, NCBI, Sage Journal, and Taylor &amp; Francis. The results showed that the total number of studies reviewed was 12 studies, with 701 patients. The types of stroke included in this study were; recurrent stroke, ischemic, infarction, intracerebral hemorrhage, and transient ischemic attack. Physical activity interventions in this literature study are aerobic exercise, walking exercise, isokinetic training, balance exercise, and aquatic-based exercise. In conclusion, regular physical activity and exercise affect chronic stroke recovery, significantly improving motor function, emotional, cardiorespiratory health, and quality of life.&#x0D; &#x0D; Keywords: Physical Exercise, Recovery, Rehabilitation, Stroke

Obstructive sleep apnea during the chronic stroke recovery period: Comparison between primary haemorrhagic and ischaemic events.

The present study retrospectively determined the incidence of obstructive sleep apnea (OSA) after a primary haemorrhagic event compared to an ischaemic stroke during the post-acute recovery period ( > 3months). Consideration of medications taken during the sleep evaluation provided additional information on the association between OSA and pathophysiological conditions that may increase the risk of a repeated cardiovascular event. The medical records from 103 patients that underwent a type I fully attended overnight polysomnography as a standard evaluation procedure at a rehabilitation facility were reviewed. Diagnosis of ischaemic or primary haemorrhagic stroke was obtained from a neurological report that was typically confirmed by imaging. Medications taken at the time of the sleep study were documented. Age-adjusted assessment of sleep-disordered breathing revealed a higher incidence of apnea and hypopnea in the ischaemic stroke group (p<0.005). Patients with ischaemic stroke were also more likely to have severe OSA (p<0.005). In comparison, a higher percentage of patients with haemorrhagic stroke had an apnea-hypopnea index <5events/hr (p<0.005). Those with an ischaemic stroke were taking more lipid lowering agents (p<0.05). Results suggest that apnea is less prevalent after a haemorrhagic stroke, independent of hypertension, compared to an ischaemic stroke. An increase in predictive values for OSA was observed for indicators of diabetes (p<0.05). These data indicate that it is relevant to consider stroke type when determining the risk of OSA during the chronic recovery period thus facilitating new strategies for stroke recurrence prevention.

CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke.

Reduced number and function of CD31+ circulating angiogenic cells (CACs) may explain vascular complications associated with the chronic phase stroke. The purpose of this study was to quantify CD31+ CAC paracrine function, total number and number of various subtypes of CD31+ CACs in individuals with chronic stroke compared with controls. Peripheral blood mononuclear cells were isolated from chronic stroke participants and controls. CD31+ cells were quantified by flow cytometry, as was co-expression of CD31 in combination with CD14, CD3, CD11b, or CD34. Immunomagnetically selected CD31+ cells were cultured, and conditioned medium was used in a capillary-like network assay. Significantly lower levels of CD31+ CACs were found in stroke participants compared with controls (-24%; P=0.04). Additionally, CD31+/CD14+, CD31+/CD11b+ and CD31+/CD3+ cells were significantly lower in the chronic stroke group compared with controls (-45%, P=0.02; -47%, P=0.02 and -32%, P=0.03, respectively). There was no group effect on CD31+ CAC conditioned media-mediated capillary-like network formation. CD31+ CACs and subtypes may serve as potential therapeutic targets in chronic stroke recovery.

Modulation of Functional Connectivity and Low-Frequency Fluctuations After Brain-Computer Interface-Guided Robot Hand Training in Chronic Stroke: A 6-Month Follow-Up Study.

Hand function improvement in stroke survivors in the chronic stage usually plateaus by 6 months. Brain-computer interface (BCI)-guided robot-assisted training has been shown to be effective for facilitating upper-limb motor function recovery in chronic stroke. However, the underlying neuroplasticity change is not well understood. This study aimed to investigate the whole-brain neuroplasticity changes after 20-session BCI-guided robot hand training, and whether the changes could be maintained at the 6-month follow-up. Therefore, the clinical improvement and the neurological changes before, immediately after, and 6 months after training were explored in 14 chronic stroke subjects. The upper-limb motor function was assessed by Action Research Arm Test (ARAT) and Fugl-Meyer Assessment for Upper-Limb (FMA), and the neurological changes were assessed using resting-state functional magnetic resonance imaging. Repeated-measure ANOVAs indicated that long-term motor improvement was found by both FMA (F[2,26] = 6.367, p = 0.006) and ARAT (F[2,26] = 7.230, p = 0.003). Seed-based functional connectivity analysis exhibited that significantly modulated FC was observed between ipsilesional motor regions (primary motor cortex and supplementary motor area) and contralesional areas (supplementary motor area, premotor cortex, and superior parietal lobule), and the effects were sustained after 6 months. The fALFF analysis showed that local neuronal activities significantly increased in central, frontal and parietal regions, and the effects were also sustained after 6 months. Consistent results in FC and fALFF analyses demonstrated the increase of neural activities in sensorimotor and fronto-parietal regions, which were highly involved in the BCI-guided training.Clinical Trial Registration: This study has been registered at ClinicalTrials.gov with clinical trial registration number NCT02323061.

Identifiable Patterns of Trait, State, and Experience in Chronic Stroke Recovery

Background Considerable evidence indicates that the functional connectome of the healthy human brain is highly stable, analogous to a fingerprint. Objective We investigated the stability of functional connectivity across tasks and sessions in a cohort of individuals with chronic stroke using a supervised machine learning approach. Methods Twelve individuals with chronic stroke underwent functional magnetic resonance imaging (fMRI) seven times over 18 weeks. The middle 6 weeks consisted of intensive aphasia therapy. We collected fMRI data during rest and performance of 2 tasks. We calculated functional connectivity metrics for each imaging run, then applied a support vector machine to classify data on the basis of participant, task, and time point (pre- or posttherapy). Permutation testing established statistical significance. Results Whole brain functional connectivity matrices could be classified at levels significantly greater than chance on the basis of participant (87.1% accuracy; P < .0001), task (68.1% accuracy; P = .002), and time point (72.1% accuracy; P = .015). All significant effects were reproduced using only the contralesional right hemisphere; the left hemisphere revealed significant effects for participant and task, but not time point. Resting state data could also be used to classify task-based data according to subject (66.0%; P < .0001). While the strongest posttherapy changes occurred among regions outside putative language networks, connections with traditional language-associated regions were significantly more positively correlated with behavioral outcome measures, and other regions had more negative correlations and intrahemispheric connections. Conclusions Findings suggest the profound importance of considering interindividual variability when interpreting mechanisms of recovery in studies of functional connectivity in stroke.

Momordica charantia polysaccharides modulate the differentiation of neural stem cells via SIRT1/\u0392-catenin axis in cerebral ischemia/reperfusion

BackgroundStroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their anti-oxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI).MethodsWe investigated MCPs’ function in differentiation of neural stem cells (NSCs) in vivo and in vitro experiments. Based on a middle cerebral artery occlusion (MCAO) rat model, the effect of MCPs on neuronal differentiation after MCAO was analyzed. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of IRI. We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation was also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1.ResultsMCPs had no effects on the differentiation of neural stem cells under physiological conditions while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCP-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs.ConclusionOur findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.

RTMS and CIMT for Neurofunctional Recovery in Chronic Stroke

Background: The purpose of the study was to investigate the effect of high frequency rTMS with constraint induced movement therapy (CIMT) on Upper extremity motor function. Clinical Stroke Assessment Scales and fMRI was used to assess the response of CIMT with rTMS on blood oxygenation-level dependent (BOLD) sequence component. Methodology: RCT was conducted at All India Institute of Medical Sciences, New Delhi, on chronic stroke patients (N=60) between 12 to 36 months of index event with atleast 10° of wrist extension, 10° of thumb abduction, Brunnstorm stage 2-4; NIHSS 4–20. Patients were randomized to CIMT alone (Group A n=30) & rTMS with CIMT (Group B n=30). rTMS (10 Hz, 750 pulses with 110%RMT) was administered for 3 weeks (5days/week). Radiological Assessment of the patients was done with fMRI (BOLD) along with assessment of Fugl Meyer (FM), Barthel Index, and modified Rankin Scales (MRS) at baseline, 3 weeks (Post intervention) & 3 month (follow up) Results: FM showed statistically significant improvement in group B as compared to group A at 3 weeks (95%CI: -12.4 to -9.3, p=0.003) and 3months (95%CI: 7.4 to 4.2, p=0.01). Repeated measure ANOVA showed that the mean groups were different at all-time points indicating some degree of improvement in all the subjects (F=3.4, p=0.01; F=5.4, p=0.002). The BOLD cluster activation was compared between two groups; there was increase in the number of clusters found in Group B. Conclusion: Both the groups showed improvement, increased cluster count showing alterations in cortical activations (fMRI-BOLD) after CIMT with rTMS in patients with chronic stroke indicated more degree of clinical improvement in upper extremity function.

Predicting clinically significant motor function improvement after contemporary task-oriented interventions using machine learning approaches

BackgroundAccurate prediction of motor recovery after stroke is critical for treatment decisions and planning. Machine learning has been proposed to be a promising technique for outcome prediction because of its high accuracy and ability to process large volumes of data. It has been used to predict acute stroke recovery; however, whether machine learning would be effective for predicting rehabilitation outcomes in chronic stroke patients for common contemporary task-oriented interventions remains largely unexplored. This study aimed to determine the accuracy and performance of machine learning to predict clinically significant motor function improvements after contemporary task-oriented intervention in chronic stroke patients and identify important predictors for building machine learning prediction models.MethodsThis study was a secondary analysis of data using two common machine learning approaches, which were the k-nearest neighbor (KNN) and artificial neural network (ANN). Chronic stroke patients (N = 239) that received 30 h of task-oriented training including the constraint-induced movement therapy, bilateral arm training, robot-assisted therapy and mirror therapy were included. The Fugl-Meyer assessment scale (FMA) was the main outcome. Potential predictors include age, gender, side of lesion, time since stroke, baseline functional status, motor function and quality of life. We divided the data set into a training set and a test set and used the cross-validation procedure to construct machine learning models based on the training set. After the models were built, we used the test data set to evaluate the accuracy and prediction performance of the models.ResultsThree important predictors were identified, which were time since stroke, baseline functional independence measure (FIM) and baseline FMA scores. Models for predicting motor function improvements were accurate. The prediction accuracy of the KNN model was 85.42% and area under the receiver operating characteristic curve (AUC-ROC) was 0.89. The prediction accuracy of the ANN model was 81.25% and the AUC-ROC was 0.77.ConclusionsIncorporating machine learning into clinical outcome prediction using three key predictors including time since stroke, baseline functional and motor ability may help clinicians/therapists to identify patients that are most likely to benefit from contemporary task-oriented interventions. The KNN and ANN models may be potentially useful for predicting clinically significant motor recovery in chronic stroke.

Effect of trunk stabilization exercises on upper limb recovery in chronic stroke

Background: The trunk being the central key point of the body, proximal trunk control may be a prerequisite for distal limb movement control and functional activities. Sitting balance and selective trunk movements remain impaired together with limbs after stroke. Selective trunk muscle exercises are administered for rehabilitation of lower limb in reference to better trunk control, but therewith of upper limb functioning isn't well established in subjects with chronic stroke. Objective: To test the consequences of trunk stabilization exercises on upper extremity recovery in chronic stroke. Method: 30 subjects with chronic stroke were randomly divided into two groups (n= 15), group I was administered conventional therapy and group II, conventional therapy together with trunk stabilization exercises for five days per week for 3 weeks. Fugl-Meyer Assessment Scale for upper extremity (FMA-UE), Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) were wont to analyse objective of this study. Results: Trunk stabilization exercises were showing significantly greater change in upper limb motor recovery and functionality than only conventional therapy intervention. Within the trunk stabilization exercise group, significant change in upper limb motor recovery (p< 0.05) and functional status (p< 0.05) with 95% confidence interval were found. There was no change found on improvising strength of activity performance in WMFT scale. Conclusion: Trunk stabilization exercises together with conventional therapy enhance upper limb recovery in subjects with chronic stroke.