[The impact of the impairment of social cognitive functions in acute stage of stroke on its functional outcomes]. / Vliyanie narushenii sotsial'nykh kognitivnykh funktsii v ostrom periode ishemicheskogo insul'ta na ego funktsional'nye iskhody.

OBJECTIVE: To analyze the influence of the impairment of social cognitive functions (SCF) in acute phase of ischemic stroke (IS) on its functional outcomes in 6 months. MATERIAL AND METHODS: One hundred patients with IS were included in the study. The assessment of social-demographic, clinical characteristics and SCF (theory of mind (ToM), affective empathy, social empathy) of the patients on the day 10 after stroke was conducted. Patients underwent standard laboratory tests of blood and urine. Functional outcomes in 6 months were recorded; score ≥3 on the modified Rankin scale (mRs) indicated unfavorable outcome. Multiple linear regression analysis was performed to identify independent predictors of functional outcomes of stroke in 6 months. RESULTS: Patients with unfavorable outcomes in 6 months after stroke in acute phase had more severe neurological deficit, more prominent disability level, lower mobility, severer impairment of SCF and lower level of total protein in biochemical analysis of blood. The independent predictors of functional outcomes of IS in 6 months included severity of the impairment of SCF (namely, ToM) according to the Reading the Mind in the Eyes test and severity of functional impairment on admission assessed by mRs. CONCLUSION: Changes of SCF, particularly of ToM, in the acute phase of IS are associated with its unfavorable functional outcomes in 6 months.

Association of Genetically Predicted Anxiety and Depression With Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.

BACKGROUND AND OBJECTIVES: Anxiety and depression have implications for ischemic stroke recovery. This study explored the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke using Mendelian randomization (MR) approach. METHODS: Independent genetic variants associated with anxiety and depression at genome-wide significance level (p < 5 × 10-8) were obtained from large-scale genome-wide association studies (Nmax = 1,306,354). Genetic results of poststroke outcome were obtained from Genetics of Ischemic Stroke Functional Outcome meta-analysis (N = 6,021). Three months after ischemic stroke event, the functional outcome was appraised with the modified Rankin Scale (mRS) score, and a mRS >2 was defined as worse functional outcome. Odds ratios (ORs) and 95% CIs are reported for the association of genetically predicted anxiety and depression with functional outcome after ischemic stroke. The inverse-variance weighted method was adopted to pool estimates. Alternative MR methods such as the weighted median and MR using the Robust Adjusted Profile Score were used as sensitivity analyses. The intercept of MR-Egger regression was also adopted to assess pleiotropy. The heterogeneity among variants was assessed by I2 and Q statistics. RESULTS: Genetic liability to depression was associated with worse functional outcome after stroke (mRS 3-6, OR 2.30; 95% CI 1.18-4.49, p = 0.015). Sensitivity analyses produced consistent results. The bidirectional MR analysis indicates that poststroke outcome did not influence liability to depression (OR 1.01, 95% CI 0.99-1.03; p = 0.436). By comparison, genetic liability to anxiety was not related with poststroke outcome (OR 1.03; 95% CI 0.71-1.50; p = 0.869). Analyses in models without adjustment for stroke severity also indicated that genetic liability to depression was related with poor functional outcome after ischemic stroke (OR 2.54; 95% CI 1.41-4.58; p = 0.002). No evidence of heterogeneity or directional pleiotropy was observed (p > 0.05). DISCUSSION: Our MR study provides evidence to support detrimental effects of depression on ischemic stroke functional outcome. Future studies are warranted to explore whether clinical intervention on depression can ameliorate functional outcome after ischemic stroke.

Associations of sedentary behaviors with mental health outcomes in a cohort of patients with minor ischemic stroke.

OBJECTIVE: The relationship between sedentary behaviors and functional outcomes of acute ischemic stroke (AIS) has been previously reported. However, it remains unclear whether sedentary behaviors are associated with mental health outcomes in AIS patients. Therefore, the objective of this study was to investigate the mental health outcomes in patients with minor AIS one year after stroke onset. METHODS: This cross-sectional study recruited 1230 patients with minor AIS (NIHSS ≤ 5) from three hospitals in China. One year after discharge, patients were interviewed using face-to-face questionnaires, including the PHQ-9, GAD-7, and ISI, to assess symptoms of depression, anxiety, and insomnia, respectively. Participants were categorized into the long sedentary time group and the short sedentary time group based on the median sedentary time of all participants. The associations between leisure sedentary time and mental health outcomes were investigated. RESULTS: Participants with a long leisure sedentary time had higher PHQ-9, GAD-7, and ISI scores than those with a short sedentary time. Longer sedentary time was associated with an increased risk of experiencing symptoms of major depression (RR, 95% CI: 1.79, 1.47 to 2.18), anxiety (RR, 95% CI: 3.28, 2.08 to 5.18), and insomnia (RR, 95% CI: 2.58, 2.03 to 3.28) one year after a minor AIS. CONCLUSION: Excessive sedentary time is associated with long-term mental health conditions after stroke. Therefore, reducing the sedentary time might be helpful for preventing poststroke depression, anxiety, and insomnia.

Incidence and Influencing Factors of Anxiety and Depression in Individuals with Acute Ischemic Stroke: A Retrospective Study.

BACKGROUND: Acute ischemic stroke (AIS) is the most common type of stroke in clinical practice, and individuals with stroke are more prone to psychological disorders than healthy individuals. This study aims to explore the incidence of anxiety and depression and related influencing factors in individuals with AIS. METHODS: In brief, 680 individuals with AIS admitted to Chun'an County First People's Hospital from January 2021 to January 2023 were selected as the research subjects, and their clinical data were retrospectively analyzed. All patients were evaluated with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to observe the occurrence of anxiety and depression, and single-factor and multi-factor logistic regression were used to analyze the influencing factors of anxiety and depression. RESULTS: Among the 680 individuals with AIS, there were 63 cases of mild anxiety (9.26%), 25 cases of moderate anxiety (3.68%), and 8 cases of severe anxiety (1.18%), with a total of 96 cases (14.12%) with anxiety symptoms. Additionally, there were 74 cases of mild depression (10.88%), 28 cases of moderate depression (4.12%), and 10 cases of severe depression (1.47%), with a total of 112 cases with depression (16.47%). The results of univariate analysis showed that there was a weak correlation between age, body mass index, disease duration, marital status, and the development of anxiety and depression in individuals with AIS (p > 0.05). Educational level, underlying diseases, family income, and place of residence were found to influence the development of anxiety and depression in individuals with AIS (p < 0.05). The results of multivariate logistic regression analysis showed that educational level (no higher education), underlying diseases (with), family income (<50,000 yuan/year, the average exchange rate of RMB to USD was 6.7261), and place of residence (rural area) were influencing factors for the development of anxiety and depression in individuals with AIS (p < 0.05). CONCLUSION: Depression and anxiety are common psychological disorders in patients with AIS. The level of education (no higher education), underlying diseases (with), family income (<50,000 yuan/year), and place of residence (rural area) were risk factors that may lead to anxiety and depression in individuals with AIS. For those with risk factors for anxiety and depression, reasonable intervention should be continually provided to guide early disease prediction and treatment of anxiety and depression in individuals with AIS.

Predictors of social risk for post-ischemic stroke reintegration.

After stroke rehabilitation, patients need to reintegrate back into their daily life, workplace and society. Reintegration involves complex processes depending on age, sex, stroke severity, cognitive, physical, as well as socioeconomic factors that impact long-term outcomes post-stroke. Moreover, post-stroke quality of life can be impacted by social risks of inadequate family, social, economic, housing and other supports needed by the patients. Social risks and barriers to successful reintegration are poorly understood yet critical for informing clinical or social interventions. Therefore, the aim of this work is to predict social risk at rehabilitation discharge using sociodemographic and clinical variables at rehabilitation admission and identify factors that contribute to this risk. A Gradient Boosting modelling methodology based on decision trees was applied to a Catalan 217-patient cohort of mostly young (mean age 52.7), male (66.4%), ischemic stroke survivors. The modelling task was to predict an individual's social risk upon discharge from rehabilitation based on 16 different demographic, diagnostic and social risk variables (family support, social support, economic status, cohabitation and home accessibility at admission). To correct for imbalance in patient sample numbers with high and low-risk levels (prediction target), five different datasets were prepared by varying the data subsampling methodology. For each of the five datasets a prediction model was trained and the analysis involves a comparison across these models. The training and validation results indicated that the models corrected for prediction target imbalance have similarly good performance (AUC 0.831-0.843) and validation (AUC 0.881 - 0.909). Furthermore, predictor variable importance ranked social support and economic status as the most important variables with the greatest contribution to social risk prediction, however, sex and age had a lesser, but still important, contribution. Due to the complex and multifactorial nature of social risk, factors in combination, including social support and economic status, drive social risk for individuals.

Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients.

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544.

Prevalence of depression and anxiety symptoms after stroke in young adults: A systematic review and meta-analysis.

BACKGROUND: Young adults with stroke have distinct professional and social roles making them vulnerable to symptoms of post-stroke depression (PSD) and post-stroke anxiety (PSA). Prior reviews have examined the prevalence of anxiety and depression in stroke populations. However, there are a lack of studies that have focused on these conditions in young adults. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies that reported on symptoms of PSD, PSA and comorbid PSD/PSA in young adults aged 18 to 55 years of age. METHODS: MEDLINE, EMBASE, SCOPUS and PsycINFO were searched for studies reporting the prevalence of symptoms of PSD and/or PSA in young adults with stroke from inception until June 23, 2023. We included studies that evaluated depression and/or anxiety symptoms with screening tools or interviews following ischemic or hemorrhagic stroke. Validated methods were employed to evaluate risk of bias. RESULTS: 4748 patients from twenty eligible studies were included. Among them, 2420 were also evaluated for symptoms of PSA while 847 participants were evaluated for both PSD and PSA symptoms. Sixteen studies were included in the random effects meta-analysis for PSD symptoms, with a pooled prevalence of 31 % (95 % CI 24-38 %). Pooled PSA symptom prevalence was 39 % (95 % CI 30-48 %) and comorbid PSD with PSA symptom prevalence was 25 % (95 % CI 12-39 %). Varying definitions of 'young adult', combinations of stroke subtypes, and methods to assess PSD and PSA contributed to high heterogeneity amongst studies. CONCLUSIONS: We identified high heterogeneity in studies investigating the prevalence of symptoms of PSD and PSA in young adults, emphasizing the importance of standardized approaches in future research to gain insight into the outcomes and prognosis of PSD and PSA symptoms following stroke in young adults. Larger longitudinal epidemiological studies as well as studies on tailored interventions are required to address the mental health needs of this important population. FUNDING: None.

Correlation of Circadian Rhythms and Improvement of Depressive Symptoms in Acute Ischemic Stroke Patients

OBJECTIVES: To investigate the correlation between evening melatonin timing secretion, dim light melatonin onset (DLMO), and post-stroke depression (PSD) in acute ischemic stroke patients and their influence on the improvement of depressive symptoms. MATERIALS AND METHODS: 120 patients with a recent magnetic resonance imaging confirmed stroke were included. Salivary melatonin samples were collected at 5 time points within 1 week after hospitalization (7 p.m.-11 p.m., 1 sample per hour). The circadian phase was defined by calculating DLMO secretion. Post-stroke depressive symptoms were evaluated by the 17-item Hamilton Rating Scale for Depression (HRSD) both on day 7 of hospitalization and 3 months after stroke. Patients were divided into PSD and non-PSD groups based on whether the acute phase HRSD score was ≥8. Similarly, patients were divided into the improved depressive symptoms (IDS) and no improvement in depressive symptoms (non-IDS) groups based on whether the HRSD score at 3 months was lower than at baseline. Neurological recovery at 3 months was assessed using the modified Rankin Scale (mRS). RESULTS: The difference in DLMO between PSD and non-PSD patients was not statistically significant (p =0.173). In the non-IDS group, there was a significant decrease in melatonin secretion at 10 p.m. (p =0.012), and DLMO was significantly later than in the IDS group (p =0.017). Logistic regression analysis showed that DLMO (OR 1.91, 95%CI:1.13-3.23, p = 0.016) was an independent risk factor for persistent no improvement in depressive symptoms, which was associated with a markedly worse prognosis (p <.001). CONCLUSION: Our findings suggest possible interventions for the very early identification of non-IDS patients.

Cognitive trajectory in the first year after first-ever ischaemic stroke in young adults: the ODYSSEY study.

BACKGROUND: Limited data exists on cognitive recovery in young stroke patients. We aimed to investigate the longitudinal course of cognitive performance during the first year after stroke at young age and identify predictors for cognitive recovery. METHODS: We conducted a multicentre prospective cohort study between 2013 and 2021, enrolling patients aged 18-49 years with first-ever ischaemic stroke. Cognitive assessments were performed within 6 months and after 1 year following the index event, covering seven cognitive domains. Composite Z-scores using normative data determined cognitive impairment (Z-score<-1.5). A Reliable Change Index (RCI) assessed cognitive recovery (RCI>1.96) or decline (RCI<-1.96). RESULTS: 393 patients (median age 44.3 years, IQR 38.4-47.2) completed cognitive assessments with a median time interval of 403 days (IQR 364-474) between assessments. Based on RCI, a similar proportion of patients showed improvement and decline in each cognitive domain, while the majority exhibited no cognitive change. Among cognitively impaired patients at baseline, improvements were observed in processing speed (23.1%), visuoconstruction (40.1%) and executive functioning (20.0%). Younger age was associated with better cognitive recovery in visuoconstruction, and larger lesion volume was related to cognitive recovery in processing speed. No other predictors for cognitive recovery were identified. CONCLUSIONS: Cognitive impairment remains prevalent in young stroke even 1 year after the event. Most patients showed no cognitive change, however, recovery may have occurred in the early weeks after stroke, which was not assessed in our study. Among initially cognitively impaired patients, cognitive recovery is observed in processing speed, visuoconstruction and executive functioning. It is still not possible to predict cognitive recovery in individual patients.

[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.

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.

Astrocytic glycogen mobilization participates in salvianolic acid B-mediated neuroprotection against reperfusion injury after ischemic stroke.

Astrocytic glycogen serves as an important glucose reserve, and its degradation provides extra support for neighboring neurons during energy deficiency. Salvianolic acid B (SAB) exerts a neuroprotective effect on reperfusion insult after cerebrovascular occlusion, but the effect of SAB on astrocytic glycogen and its relationship with neuroprotection are not completely understood. Here, we knocked down astrocyte-specific glycogen phosphorylase (GP, the rate-limiting enzyme in glycogenolysis) in vitro and in vivo and investigated the changes in key enzymes in glycogen metabolism by performing immunoblotting in vitro and immunofluorescence in vivo. Neurobehavioral and morphological assessments were conducted to uncover the outcomes during brain reperfusion. SAB accelerated astrocytic glycogenolysis by upregulating GP activity but not GP expression after reperfusion. Suppression of astrocytic glycogenolysis weakened SAB-mediated neuroprotection against the reperfusion insult. In addition, activation of glycogenolysis by SAB contributed to the survival of astrocytes and surrounding neurons by increasing antioxidant levels in astrocytes. Our data reveal that astrocytic GP represents an important metabolic target in SAB-induced protection against brain damage after cerebrovascular recanalization.

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

BACKGROUND AND PURPOSE: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. METHODS: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. RESULTS: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. CONCLUSIONS: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Sex differences in the cerebroprotection by Nestorone intranasal delivery following stroke in mice.

Our previous studies showed that intranasal delivery of progesterone offers a good bioavailability and neuroprotective efficacy after experimental stroke. We have also demonstrated that progesterone receptors (PR) are essential for cerebroprotection by endogenous progesterone and by progesterone treatment. The identification of PR as a potential drug target for stroke therapy opens new therapeutic indications for selective synthetic progestins. Nestorone® (16-methylene-17α-acetoxy-19-nor-pregn-4-ene-3, 20-dione, also known as segesterone acetate) is a 19-norprogesterone derivative that more potently targets PR than progesterone. The objective of this study was to evaluate the cerebroprotective efficiency of intranasal administration of Nestorone after middle cerebral occlusion (MCAO) in mice. We show here that intranasal administration is a very efficient route to achieve a preferential delivery of Nestorone to the brain and confers a slow elimination and a sustained bioavailability. Furthermore, intranasal administration of Nestorone (at 0.08 mg/kg) improved the functional outcomes and decreased the ischemic lesion in male but not in female mice at 48 h post MCAO. Use of PRNesCre mice, selectively lacking expression of PR in neural cells, and their control PRloxP/loxP littermates showed that the cerebroprotective effects of Nestorone in male mice depended on neural PR as they were not observed in PRNesCre mice. Our findings show that intranasal delivery of Nestorone may be an efficient strategy to promote recovery after stroke in males and confirm the key role of PR in cerebroprotection. Furthermore, they point to sex differences in the response to Nestorone treatment and emphasize the necessity to include males and females in experimental studies.

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.

Temporal Changes in Cognitive Function in Early Recovery Phase of the Stroke.

OBJECTIVES: Only a few studies longitudinally evaluated all cognitive domains after acute stroke. The purpose was to study the changes in cognitive function after acute stroke. MATERIALS AND METHODS: Cognitive assessment, using Thai mental state examination (TMSE) and Montreal Cognitive Assessment (MOCA), was performed at the acute stroke, and at 3 and 6 months after stroke. Cognitive domains were evaluated by MOCA subcategory score. TMSE and MOCA were compared at different stages of stroke and in among those with normal cognition (NC), vascular mild cognitive impairment (VMCI) and vascular dementia (VAD). RESULTS: 138 patients were included. At 6 months, 32 patients (23%) had NC. VMCI and VAD were diagnosed in 76 patients (55%), and 30 patients (22%), respectively. Total scores of TMSE and MOCA were higher at 3 months as compared to at the acute stroke (TMSE; 24.85 vs 23.01, p-value <0.001, MOCA; 19.30 vs 16.49, p-value <0.001), and higher TMSE, but not MOCA, at 6 months as compared to at 3 months (TMSE; 25.35 vs 24.85, p-value= 0.021, MOCA; 19.04 vs 19.30, p-value= 0.058). Changes in total scores at early stroke were highest in NC. VMCI and VAD patients had cognitive impairment in all cognitive domains. CONCLUSIONS: Cognitive impairment was highest at the acute stroke and improved during early recovery. The greatest rate of improvement occurred within 3 months. Improvement was found in all cognitive domains.

Neuronal CD200 Signaling Is Protective in the Acute Phase of Ischemic Stroke.

Background and Purpose: CD200 (cluster of differentiation 200), a highly glycosylated protein primarily expressed on neurons in the central nervous system, binds with its receptor CD200R to form an endogenous inhibitory signal against immune responses. However, little is known about the effect of neuronal CD200 signaling in cerebral ischemia. The aim of this study was to investigate how neuronal CD200 signaling impacts poststroke inflammation and the ischemic injury. Methods: CD200 tma1lf/fl:Thy1CreER mice were treated with tamoxifen to induce conditional gene knockout (ICKO) of neuronal CD200. The mice were subjected to a 60-minute transient middle cerebral artery occlusion. Stroke outcomes, apoptotic cell death, immune cell infiltration, microglia activation, and other inflammatory profiles were evaluated at 3 and 7 days after stroke. Results: Infarct volumes were significantly larger, and behavioral deficits more severe in ICKO versus control mice at 3 days after middle cerebral artery occlusion. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay also revealed a significant increase in apoptotic neuronal death in CD200 ICKO mice. An enhancement in lymphocytic infiltration and microglial proinflammatory responses were revealed by flow cytometry at 3 and 7 days after stroke in ICKO mice, accompanied by an increased microglial phagocytosis activity. Plasma proinflammatory cytokine (TNFα [tumor necrosis factor alpha] and IL [interleukin]-1ß) levels significantly increased at 3 days, and IL-1ß/IL-6 levels increased at 7 days in ICKO versus control animals. ICKO led to significantly lower baseline level of CD200 both in brain and plasma. Conclusions: Neuronal CD200 inhibits proinflammatory responses and is protective against stroke injury.

Pre-hospital causes for delayed arrival in acute ischemic stroke before and during the COVID-19 pandemic: A study at two stroke centers in Egypt.

BACKGROUND: In the current study we investigated the causes of pre-hospital delay as this can compromise the patient's chance to receive thrombolytic therapy and thus impact stroke outcome. METHODS: We surveyed 254 patients regarding reasons for delayed and early arrival to hospital after acute ischemic stroke. The survey was performed over five months, spanning a period pre- and during COVID-19 (between December 7, 2019 and May 10, 2020). RESULTS: A total of 71.2% of patients arrived beyond four hours of onset of ischemic stroke. The commonest cause for delay pre-Covid-19 was receiving treatment in a non-stroke hospital, while that during COVID-19 was fear of infection and lock down issues. Not realizing the urgency of the condition and stroke during sleep were common in both periods. Early arrival because of the patient's previous experience with stroke accounted for approximately 25% of cases in both periods. The effect of media was more evident during COVID-19, accounting for 47.7% of cases. CONCLUSION: Pre-hospital delay secondary to misperception of the urgency of stroke and management in a non-stroke hospital reflect the lack of awareness among the public and medical staff. This concept is emphasized by early arrival secondary to previous experience with stroke and the pronounced effect of media in the time of COVID-19.

Prevalence and Predictors of Fatigue and Neuropsychiatric Symptoms in Patients with Minor Ischemic Stroke.

OBJECTIVES: Patients who are victims of a mild stroke are vulnerable to several invisible and neglected neurological sequelae. In parallel, it is known that fatigue and neuropsychiatric symptoms are common complications after a stroke in general. Our aim was to describe the prevalence and the factors associated with these two outcomes after a minor stroke. MATERIALS AND METHODS: We conducted a prospective observational cohort study that included consecutive patients diagnosed with minor ischemic stroke between 2015 and 2019. Minor stroke was defined as NIHSS < 4 and modified Rankin Scale (mRS) < 2. Patients were followed for 12 months after the index stroke. The primary endpoints included fatigue and neuropsychiatric impairment, which were evaluated with the Fatigue Severity Scale (FSS) and the Hospital Anxiety Depression Scale (HADS), respectively. RESULTS: A total of sixty patients were followed in our cohort. The mean age was 53.0 (SD 15.0) and 51.7% were male. There were 32 (53.3%) and 25 (41.7%) patients who developed PSF and post-stroke neuropsychiatric symptoms, respectively. The use of antidepressants and statins were associated with post-stroke fatigue, while women and younger patients were more likely to develop neuropsychiatric symptoms after the stroke (p < 0.05). Eighteen (30.0%) patients were diagnosed with both post-stroke fatigue and psychiatric disorders. CONCLUSIONS: Post-stroke fatigue and neuropsychiatric symptoms are prevalent in minor stroke and should be independently addressed as a part of the recovery goal.

Synthesis and biological evaluation of 1,2,4-oxadiazole core derivatives as potential neuroprotectants against acute ischemic stroke.

Here, we report the synthesis and neuroprotective capacity of 27 compounds with a bisphenol hydroxyl-substituted 1,2,4-triazole core or 1,2,4-oxadiazole core for stroke therapy. In vitro studies of the neuroprotective effects of compounds 1-27 on sodium nitroprusside (SNP)-induced apoptosis in PC12 cells indicate that compound 24 is the most effective compound conferring potent protection against oxidative injury. Compound 24 inhibits reactive oxygen species (ROS） accumulation and restores the mitochondrial membrane potential (MMP). Moreover, further analysis of the mechanism showed that compound 24 activates the antioxidant defence system by promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increasing the expression of haem oxygenase 1 (HO-1). An in vivo study was performed in a rat model of transient focal cerebral ischaemia generated by the intraluminal occlusion of the middle cerebral artery (MCAO). Compound 24 significantly reduced brain infarction and improved neurological function. Overall, compound 24 potentially represents a promising compound for the treatment of stroke.