[Rehabilitation of patients with post-stroke cognitive impairment using the P300-based brain-computer interface: results of a randomized controlled trial]. / Reabilitatsiya patsientov s postinsul'tnymi kognitivnymi narusheniyami s ispol'zovaniem interfeisa «mozg­komp'yuter¼ na volne P300: rezul'taty randomizirovannogo kontroliruemogo issledovaniya.

OBJECTIVE: To study the effects of a 10-day cognitive training using the brain-computer interface (BCI) technology at the P300 wavelength on the recovery of cognitive functions in poststroke patients. MATERIAL AND METHODS: The study included 30 patients, aged 22-82 years, with ischemic stroke less than 3 months old and moderate cognitive impairment (<26 points on the Montreal Cognitive Assessment Scale (MoCA)). All patients underwent neuropsychological testing, assessment of the presence of depression, assessment of activity in daily life. Patients were randomized into two groups: patients of group 1 (main) underwent a 10-day course of cognitive rehabilitation in the form of daily exercises in the BCI environment at the P300 wave equipped with a headset for recording an electroencephalogram (EEG). Patients of group 2 (control) received a standard set of rehabilitation measures. RESULTS: There was an increase in the mean score of the MoCA «Attention¼ domain in the main group of patients (2.3±1.24 to 5.2±1.16 points) compared with the control group (5.9±1.00 to 4.2±0.94 points, p<0.05). The results of covariance analysis with repeated measures, taking into account the factors «Visit¼ and «Group¼, the covariate «Depression¼ and «Number of training sessions¼ revealed significant effects for the MoCA domains «Naming¼ (p<0.05), «Attention¼ (p<0.05), «Abstraction¼ (p<0.05). By the end of the 10-day cognitive training using BCI, patients of the main group showed a significant increase in the number of entered letters (20.8±2.01 to 25.9±1.7 characters (p=0.02) compared with the control group (21.9±1.9 to 23.1±1.8, p=0.06). When comparing the number of words entered by patients after 10 days, a significant difference was found between the main and control groups (p<0.05). CONCLUSION: Rehabilitation of patients with post-stroke cognitive impairment using P300 BCI has a significant positive effect on the restoration of cognitive functions, primarily attention.

Advances in the Diagnosis and Treatment of Pediatric Arterial Ischemic Stroke.

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain.

Rehabilitation Training Can Significantly Increase the Serum IL-11 Levels and Improve the Prognosis in Ischemic Stroke Patients.

We aimed to explore the expression of IL-11 in ischemic stroke patients and its correlation with rehabilitation training and prognosis. The present randomized control study recruited ischemic stroke patients who were admitted during March 2014 to November 2020. All patients underwent computer tomography (CT) and magnetic resonance imaging (MRI) examination. All patients were randomly divided into two groups, including rehabilitation training (RT) group and control group. The patients in the RT group were received rehabilitation training within 2 days after the vital signs were stable while control group received routine nursing. The serum interleukin- (IL-) 11 levels were measured by enzyme-linked immunosorbent assay (ELISA) when patients were just hospitalized and 6 h, 24 h, 48 h, 72 h, and 90 h after treatment. Demographic, clinical statistics, imaging data, and the National Institutes of Health Stroke Scores (NIHSS) were recorded. The modified Rankin Scale (mRS) scores were measured after 90 days treatment to assess the prognosis of ischemic patients. The serum IL-11 levels of the RT group elevated more quickly during the study time compared with the control group. In addition, the NIHSS and mRS scores of ischemic stroke patients in the RT group were significantly lower than that in the control group. The NIHSS score, the proportion receiving rehabilitation training, and the levels of IL-11, triglyceride (TG), and high-density leptin cholesterol (HDLC) of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than that in the mRS score ≤ 2 group. However, the serum IL-11 levels of ischemic stroke patients were obviously decreased in the mRS score ≥ 3 group. IL-11 could be a potential diagnostic biomarker of poor prognosis of ischemic stroke patients. Furthermore, IL-11, NIHSS score, and rehabilitation training were the risk factors for poor prognosis of ischemic stroke patients. This study demonstrated that the ischemic stroke patients in the RT group had higher serum IL-11 levels and better prognosis. This study might provide a new approach to improve the prognosis of patients with ischemic stroke. This trial is registered with ChiCTR-PNR-16007706.

Effects on sedentary behaviour of an approach to reduce sedentary behaviour in patients with minor ischaemic stroke: A randomised controlled trial.

OBJECTIVES: To determine the effects on sedentary behaviour of an approach that promotes reduction in sedentary behaviour in patients with minor ischaemic stroke after intervention and at follow-up. DESIGN: A randomised controlled trial. SETTING: During hospitalisation and after hospital discharge. SUBJECTS: In total, 86 patients with minor ischaemic stroke admitted to an acute care hospital were assigned to the intervention (n = 43) and control (n = 43) groups. INTERVENTION: An intervention group that received an approach to reduce sedentary behaviour upon hospital admission until 3 months after discharge (education, self-monitoring, phone calls, etc.) and a control group that received the usual care during hospitalisation. From 3 to 6 months after discharge, no group received any intervention. MAIN OUTCOME: The primary outcome was the change (%) in sedentary behaviour from baseline to post-intervention (3 months after discharge) and follow-up (6 months after discharge). Sedentary behaviour was measured at baseline (upon hospital admission), post-intervention, and at follow-up using accelerometers. RESULTS: At the post-intervention stage, the intervention group showed a significantly greater change in sedentary behaviour from baseline than that shown by the control group (sedentary behaviour: intervention group, -22.7%; control group, -14.9%; P = 0.013; effect size = 0.58). At follow-up too, the intervention group showed a significantly greater change in sedentary behaviour from baseline than that shown by the control group (sedentary behaviour: intervention group, -20.4%; control group, -13.6%; P = 0.025; effect size = 0.54). CONCLUSIONS: An approach to reduce sedentary behaviour in patients with minor ischaemic stroke effectively reduces sedentary behaviour, which is sustained up to follow-up. TRIAL REGISTRATION: This study is registered at www.umin.ac.jp/ctr/index/htm UMIN000038616.

Are There Differences in Long-Term Functioning and Recovery Between Hemorrhagic and Ischemic Stroke Patients Receiving Rehabilitation?

OBJECTIVE: Previous research suggested better recovery in functioning of patients with hemorrhagic as compared to ischemic stroke. Now that more effective acute treatment for ischemic stroke, i.e. thrombolysis and thrombectomy, has become available, this observational cohort study aimed to examine if current rehabilitation outcomes differ between patients with hemorrhagic and ischemic stroke. MATERIALS AND METHODS: The Barthel Index, 4 domains of the Stroke Impact Scale (SIS) and the EuroQol 5Dimensions were completed in all consecutive patients who received stroke rehabilitation at start of rehabilitation and during follow-up (for Barthel Index at discharge, SIS and EuroQol 5D after three and six months). Outcomes and recovery (i.e. change of scores between baseline and last follow-up) were compared between patients with hemorrhagic stroke and ischemic stroke (total and categorized by initial hospital treatment) using the Kruskall Wallis test. In addition, recovery was compared between ischemic and hemorrhagic stroke in multiple regression analyses with bootstrapping. RESULTS: Baseline functioning did not differ between 117 patients with a hemorrhagic stroke, 118 ischemic stroke patient treated with reperfusion therapy, and 125 ischemic stroke patients without reperfusion therapy. There were no differences in functioning at follow-up nor in recovery concerning the Barthel Index, SIS domains 'mobility', 'communication', 'memory and thinking' and 'mood and emotions', and EuroQoL 5D between the three categories. CONCLUSIONS: In a rehabilitation population the recovery and functioning at three or six months did not differ between ischemic stroke patients and hemorrhagic stroke patients, regardless of the hospital treatment they had received.

Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.

BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that "non-pharmacological" approaches might provide new opportunities for stroke therapy, such as electro-/acupuncture, hyperbaric oxygen therapy, hypothermia/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic/rehabilitative interventions, described as non-invasive and non-pharmacological.

Sex-differences in psychosocial sequelae after spontaneous cervical artery dissection.

Short- to mid-term functional outcome in spontaneous cervical artery dissection is favorable, but the concomitant psychosocial impact is underreported. We aimed to determine these possible sequelae, with a special focus on sex differences, in our cohort of spontaneous cervical artery dissection subjects. During a standardized prospective in-house follow-up visit we, among other values, evaluated functional outcome (modified Rankin Scale [mRS]), psychosocial measures (return to work-, divorce rate) and health-related quality of life (WHO-QoL-BREF and SF-36-questionnaires). 145 patients participated in the long-term prospective follow-up. Median follow-up time was 6.5 years and excellent functional outcome (mRS ≤ 1) was achieved in 89.0% subjects. 87.6% returned to work and 17.6% married patients had a divorce during follow-up. Even though relevant baseline-/discharge characteristics and functional outcome did not differ between the sexes, women were less likely to return to work compared to men (79.7% vs. 93.8%; P = 0.010) and divorce rate was considerably higher in women (30.2% vs. 9.2%; P = 0.022). Health related quality of life did not differ significantly between the sexes, but women consistently reported lower values. Even though functional outcome is beneficial in most patients, measures to prevent poor psychosocial outcome should be considered in the long-term care of patients with spontaneous cervical artery dissection, especially women.

Different training patterns at recovery stage improve cognitive function in ischemic stroke rats through regulation of the axonal growth inhibitor pathway.

Running wheel exercise training (RWE) and skilled reaching training (SRT) are physical training approaches with positive effects on cognitive function. However, few studies have compared the different effects of these exercises on long-term memory, and their mechanism remains unknown. This study investigated the effects of SRT and RWE, at the recovery stage, on the cognitive function of transient middle cerebral artery occlusion (tMCAO) rats and explored their association with NgR1/Rho-A/ROCK/LOTUS/LGI1 signaling. Adult Sprague-Dawley rats (n = 55) were divided into four groups after pretraining: SRT, RWE, tMCAO, and Sham. Rats were subjected to modified neurological severity score (mNSS) measurements and forelimb grip strength and the Morris water maze tests. Using immunofluorescence and western blotting, we evaluated axonal growth inhibitor expression in the peri-infarct cortex on days 28 and 56 after tMCAO. Results showed the mNSS reduced, whereas the grip strengths improved in RWE and SRT groups. The escape latency in the Morris water maze test was shorter, whereas the number of times of crossing the platform was higher in both the SRT and RWE groups than in the tMCAO group on day 56; furthermore, the parameters in the SRT group improved compared to those in the RWE group. Physical exercise training could improve cognitive functions by reducing the expression of the NgR1/RhoA/ROCK axon growth inhibitors and increasing the expression of the endogenous antagonists LOTUS/LGI1. Exercise training beginning at the recovery stage could improve the cognitive function in tMCAO rats through a mechanism probably associated with the axonal growth inhibitor pathway.

Rehabilitative training paired with peripheral stimulation promotes motor recovery after ischemic cerebral stroke.

Spontaneous recovery of ischemic stroke is very limited and often results in the loss of motor and sensory function. Till now, rehabilitative training is the most widely accepted therapy to improve long-term outcome. However, its effectiveness is often suboptimal, largely due to a sharp decline of neuroplasticity in adults. In this study, we hypothesized that a combination of proprioceptive stimulation and rehabilitative training will promote neuroplasticity and functional recovery post injury. To test this hypothesis, we first established a photothrombotic stroke model that lesions the hindlimb sensorimotor cortex. Next, we demonstrated that injecting Cre-dependent AAV-retro viruses into the dorsal column of PV-Cre mice achieves specific and efficient targeting of proprioceptors. With chemogenetics, this method enables chronic activation of proprioceptors. We then assessed effects of combinatorial treatment on motor and sensory functional recovery. Our results showed that pairing proprioceptive stimulation with rehabilitative training significantly promoted skilled motor, but not tactile sensory functional recovery. This further led to significant improvement when compared to rehabilitation training or proprioceptor stimulation alone. Mechanistically, combinatorial treatment promoted cortical layer V neuronal mTOR activity and sprouting of corticospinal axon into the area where proprioceptive afferents terminate in the denervated side of the spinal cord. Serving as a proof of principle, our study thus provided novel insights into the application of combining proprioceptive stimulation and rehabilitative training to improve functional recovery of ischemic stroke and other traumatic brain or spinal cord injuries.

Combining Optogenetic Stimulation and Motor Training Improves Functional Recovery and Perilesional Cortical Activity.

Background. An ischemic stroke is followed by the remapping of motor representation and extensive changes in cortical excitability involving both hemispheres. Although stimulation of the ipsilesional motor cortex, especially when paired with motor training, facilitates plasticity and functional restoration, the remapping of motor representation of the single and combined treatments is largely unexplored. Objective. We investigated if spatio-temporal features of motor-related cortical activity and the new motor representations are related to the rehabilitative treatment or if they can be specifically associated to functional recovery. Methods. We designed a novel rehabilitative treatment that combines neuro-plasticizing intervention with motor training. In detail, optogenetic stimulation of peri-infarct excitatory neurons expressing Channelrhodopsin 2 was associated with daily motor training on a robotic device. The effectiveness of the combined therapy was compared with spontaneous recovery and with the single treatments (ie optogenetic stimulation or motor training). Results. We found that the extension and localization of the new motor representations are specific to the treatment, where most treatments promote segregation of the motor representation to the peri-infarct region. Interestingly, only the combined therapy promotes both the recovery of forelimb functionality and the rescue of spatio-temporal features of motor-related activity. Functional recovery results from a new excitatory/inhibitory balance between hemispheres as revealed by the augmented motor response flanked by the increased expression of parvalbumin positive neurons in the peri-infarct area. Conclusions. Our findings highlight that functional recovery and restoration of motor-related neuronal activity are not necessarily coupled during post-stroke recovery. Indeed the reestablishment of cortical activation features of calcium transient is distinctive of the most effective therapeutic approach, the combined therapy.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Cerebral blood flow and cognitive outcome after pediatric stroke in the middle cerebral artery.

Adaptive recovery of cerebral perfusion after pediatric arterial ischemic stroke (AIS) is sought to be crucial for sustainable rehabilitation of cognitive functions. We therefore examined cerebral blood flow (CBF) in the chronic stage after stroke and its association with cognitive outcome in patients after pediatric AIS. This cross-sectional study investigated CBF and cognitive functions in 14 patients (age 13.5 ± 4.4 years) after pediatric AIS in the middle cerebral artery (time since AIS was at least 2 years prior to assessment) when compared with 36 healthy controls (aged 13.8 ± 4.3 years). Cognitive functions were assessed with neuropsychological tests, CBF was measured with arterial spin labeled imaging in the anterior, middle, and posterior cerebral artery (ACA, MCA, PCA). Patients had significantly lower IQ scores and poorer cognitive functions compared to healthy controls (p < 0.026) but mean performance was within the normal range in all cognitive domains. Arterial spin labeled imaging revealed significantly lower CBF in the ipsilesional MCA and PCA in patients compared to healthy controls. Further, we found significantly higher interhemispheric perfusion imbalance in the MCA in patients compared to controls. Higher interhemispheric perfusion imbalance in the MCA was significantly associated with lower working memory performance. Our findings revealed that even years after a pediatric stroke in the MCA, reduced ipsilesional cerebral blood flow occurs in the MCA and PCA and that interhemispheric imbalance is associated with cognitive performance. Thus, our data suggest that cerebral hypoperfusion might underlie some of the variability observed in long-term outcome after pediatric stroke.

Effects of Different Intervention Time Points of Early Rehabilitation on Patients with Acute Ischemic Stroke: A Single-Center, Randomized Control Study.

OBJECTIVE: To investigate effects of different intervention time points of early rehabilitation on patients with acute ischemic stroke. METHODS: We enrolled patients diagnosed with acute ischemic stroke in our hospital's rehabilitation ward from November 2013 to December 2015. Patients were randomly assigned to an ultraearly rehabilitation program (started within 72 hours of onset) or an early rehabilitation program (started from 72 hours to 7 days after onset). The efficacy was assessed by the NIH Stroke Scale (NIHSS) International, Barthel Index, and Fugl-Meyer Assessment at one and three months after rehabilitation. Data were analyzed by variance analysis of two-factor repeated measurement. Covariance analysis was used to adjust confounding factors for the determination of statistical differences. RESULTS: 41 patients were enrolled in the ultraearly rehabilitation group, while 45 patients were in the early rehabilitation group. There were no differences between the two groups at baseline data. Compared with the early rehabilitation group, patients in the ultraearly rehabilitation group have significantly improved NIHSS score, BMI score, and FMA score at one month and three months (P < 0.001). After adjusting for confounding factors (gender, age, severity of NIHSS score, location of stroke, hypertension, diabetes, atrial fibrillation, and coronary heart disease), the significant difference still existed between the two groups at one month and three months (P < 0.001). CONCLUSION: Our study indicated a higher efficacy in the ultraearly rehabilitation group than the early rehabilitation group. The result suggests an important practical significance in favor of the clinical treatment of stroke.

Grip training improves handgrip strength, cognition, and brain white matter in minor acute ischemic stroke patients.

OBJECTIVE: A large proportion of stroke patients experience cognitive impairment. Previous studies found that handgrip training can improve cognitive dysfunction after stroke through an unknown mechanism. In this study, we aimed to examine the influence of handgrip training on the cognition of patients with acute mild ischemic stroke and explore the mechanism using an advanced post-processing method for magnetic resonance imaging. METHODS: Seventy-six patients with acute mild ischemic stroke were recruited for this study and randomly divided into a grip training group (n = 37) and a control group (n = 39). Both groups of patients also received standardized treatment for stroke in the acute phase and for secondary prevention, as well as conventional physical therapy after stroke. Grip strength, global cognitive function, and the local and global efficiencies of white matter networks derived from diffusion tensor images were measured before and after the 12-week training period. RESULTS: In the within-group comparisons, grip training significantly improved the grip strength (3.52 [3.09-3.96], p = 0.02), Montreal Cognitive Assessment (MoCA) (2.27 [1.68-2.86], p = 0.05), and local, but not global, efficiency of the brain white matter network (0.03 [0.02-0.03], p = 0.02) in the experimental group. In contrast, these parameters were not statistically different over the same period in the control group. In the between-groups comparisons, the improvement of grip strength (2.71 [2.20-3.21], p = 0.01), MoCA (1.17 [0.39-1.95], p = 0.05), and local efficiency (0.02 [0.01-0.03], p = 0.01) showed statistically significant differences after the intervention, but not the absolute value of them, neither at the base line nor after the intervention. CONCLUSIONS: Our results indicate that grip training can improve cognitive function by increasing the local efficiency of brain white matter connectivity. This suggests that white matter remodeling is a potential physiological mechanism connecting grip training and cognition improvement.

Current treatment for childhood arterial ischaemic stroke.

Paediatric arterial ischaemic stroke is an important cause of neurological morbidity in children, with consequences including motor disorders, intellectual impairment, and epilepsy. The causes of paediatric arterial ischaemic stroke are unique compared with those associated with stroke in adulthood. The past decade has seen substantial advances in paediatric stroke research and clinical care, but many unanswered questions and controversies remain. Shortage of prospective evidence for the use of recanalisation therapies in patients with paediatric stroke has resulted in little standardisation of disease management. Substantial time delays in diagnosis and treatment continue to challenge best possible care. In this Review, we highlight on some of the most pressing and productive aspects of research in the treatment of arterial ischaemic stroke in children, including epidemiology and cause, rehabilitation, secondary stroke prevention, and treatment updates focusing on advances in hyperacute therapies such as intravenous thrombolysis, mechanical thrombectomy, and critical care. Finally, we provide a future perspective for improving outcomes and quality of life for affected children and their families.

Revisiting the Proportional Recovery Model in View of the Ceiling Effect of Fugl-Meyer Assessment.

Background and Purpose: The aim of this study was to verify the validity of the proportional recovery model in view of the ceiling effect of the Fugl-Meyer Assessment. Methods: We reviewed the medical records of patients enrolled in the Korean Stroke Cohort for Functioning and Rehabilitation between August 2012 and May 2015. Recovery proportion was defined as the actual change in Fugl-Meyer Assessment score of the upper extremity between 7 days and 6 months poststroke, relative to the initial neurological impairment. We then used logistic regression to identify clinical factors attributable to a ceiling effect of the Fugl-Meyer Assessment score of the upper extremity and propensity score matching to verify the validity of the proportional recovery rule. Results: We screened 10 636 patients and analyzed 849 patients (mean age, 65.4±11.9 years; female, 320 [37.7%]) with first-ever ischemic stroke. We found, through logistic regression analysis, that a one-unit increase in the initial neurological impairment and the age at stroke onset affected the odds ratio (1.0386 and 0.9736, respectively) of achieving the full Fugl-Meyer Assessment score of the upper limb at 6 months poststroke. We also demonstrated, through propensity score matching, that the difference in initial neurological impairment of the upper extremity resulted in discrepancy of the recovery proportion (0.92±0.20 [0­1] versus 0.81±0.31 [0­1], P<0.001). Conclusions: We demonstrated that the ceiling effect of the Fugl-Meyer Assessment score of the upper extremity is pronounced in patients with mild initial motor deficits of the upper extremity and that the recovery proportion varies according to the initial motor deficit of the upper limb using logistic regression analysis and propensity score matching, respectively. These results suggest that the proportional recovery model is not valid.

Effect of Sleep-Disordered Breathing During Rapid Eye Movement Sleep and Non-Rapid Eye Movement sleep on Acute Ischemic Stroke.

OBJECTIVES: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes. MATERIALS AND METHODS: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death. RESULTS: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes. CONCLUSIONS: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.

Calorie restriction conferred improvement effect on long-term rehabilitation of ischemic stroke via gut microbiota.

Calorie restriction can modulate the gut microbiota and protect against many diseases including ischemic stroke. However, the role of calorie-restriction-induced microbiota alteration remained unknown in ischemic stroke rehabilitation. Here we conducted 30% reduction of caloric intake on mice for four weeks, to evaluate its role on ischemic stroke rehabilitation. Significantly, this calorie restriction led to better long-term rehabilitation in comparison of normal control. Notably, the transplantation of gut microbiome from calorie-restriction-treated mice to post-stroke mice was eligible to obtain better long-term rehabilitation of stroke mice. Bifidobacterium identified by 16 S ribosomal RNA sequencing were enriched in those of calorie-restriction mice. Then we administrated Bifidobacterium to stroke mice and found Bifidobacterium treatment could successfully improve the long-term rehabilitation of cerebral ischemia mice. Furthermore, the metabolomics analysis revealed a panel of upshifting metabolites, suggesting that calorie restriction greatly altered the gut microbiota composition and its metabolism. Hence, we discovered the novel effect of CR on long-term rehabilitation of ischemic stroke and the underlying role of gut microbiota, which might provide novel thoughts for the clinical post-stroke rehabilitation.

The smoking paradox in ischemic stroke patients treated with intra-arterial thrombolysis in combination with mechanical thrombectomy-VISTA-Endovascular.

BACKGROUND: The smoking-paradox of a better outcome in ischemic stroke patients who smoke may be due to increased efficacy of thrombolysis. We investigated the effect of smoking on outcome following endovascular therapy (EVT) with mechanical thrombectomy alone versus in combination with intra-arterial (IA-) thrombolysis. METHODS: The primary endpoint was defined by three-month modified Rankin Scale (mRS). We performed a generalized linear model and reported relative risks (RR) for smoking (adjustment for age, sex, hypertension, atrial fibrillation, stroke severity, time to EVT) in patient data stemming from the Virtual International Stroke Trials Archive-Endovascular database. RESULTS: Among 1,497 patients, 740(49.4%) were randomized to EVT; among EVT patients, 524(35.0%) received mechanical thrombectomy alone and 216(14.4%) received it in combination with IA-thrombolysis. Smokers (N = 396) had lower mRS scores (mean 2.9 vs. 3.2; p = 0.02) and mortality rates (10% vs. 17.3%; p<0.001) in univariate analysis. In all patients and in patients treated with mechanical thrombectomy alone, smoking had no effect on outcome in regression analyses. In patients who received IA-thrombolysis (N = 216;14%), smoking had an adjusted RR of 1.65 for an mRS≤1 (95%CI 0.77-3.55). Treatment with IA-thrombolysis itself led to reduced RR for favorable outcome (adjusted RR 0.30); interaction analysis of IA-thrombolysis and smoking revealed that non-smokers with IA-thrombolysis had mRS≤2 in 47 cases (30%, adjusted RR 0.53 [0.41-0.69]) while smokers with IA-thrombolysis had mRS≤2 in 23 cases (38%, adjusted RR 0.61 [0.42-0.87]). CONCLUSIONS: Smokers had no clear clinical benefit from EVT that incorporates IA-thrombolysis.

Institutional Postacute Care Use May Help Reduce Readmissions for Ischemic Stroke Patients.

OBJECTIVES: Readmissions for Medicare patients initially admitted for stroke are common and costly. Rehabilitation in an institutional postacute care (PAC) setting is an evidence-based component of recovery for stroke. Under current Medicare payment reforms, care coordination across hospitals and PAC providers is key to improving quality and efficiency of care. We examined the causal impact of institutional PAC use on 30-day readmission rates for Medicare fee-for-service patients initially admitted for ischemic stroke. DATA SOURCES: The 2010-2016 Medicare Provider Analysis and Review files. RESEARCH DESIGN: We used the method of instrumental variable (IV) analysis to control for unobserved differences in the types of patients admitted to each PAC facility. We chose the distance from the patient's residence to the closest institutional PAC provider and the number of PAC providers of each type within a county where the patient resides as IVs. PRINCIPAL FINDINGS: In the naive model, an increase in institutional PAC use was significantly associated with an increase in 30-day readmission by 0.03 percentage points. However, using IV analysis to control for endogeneity bias, an increase in institutional PAC use was associated with a decrease in 30-day readmission rate by 0.19 percentage points. Our findings indicate that reducing institutional PAC use among patients typically requiring rehabilitation in institutional settings for recovery may potentially lead to adverse postdischarge outcomes that require rehospitalization. Thus, payment incentives to reduce institutional PAC use should be balanced with postdischarge outcomes among ischemic stroke patients.