[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.

Evaluation of Peptide Ligation Strategies for the Synthesis of the Bivalent Acid-Sensing Ion Channel Inhibitor Hi1a.

Hi1a is a naturally occurring bivalent spider-venom peptide that is being investigated as a promising molecule for limiting ischemic damage in strokes, myocardial infarction, and organ transplantation. However, the challenges associated with the synthesis and production of the peptide in large quantities have slowed the progress in this area; hence, access to synthetic Hi1a is an essential milestone for the development of Hi1a as a pharmacological tool and potential therapeutic.

[Progress in application of adult endogenous neurogenesis in brain injury repair].

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

The autophagy in ischemic stroke: A regulatory role of non-coding-RNAs.

Ischemic stroke (IS) is a central nervous system neurological disorder ascribed to an acute focal trauma, with high mortality and disability, leading to a heavy burden on family and society. Autophagy is a self-digesting process by which damaged organelles and useless proteins are recycled to maintain cellular homeostasis, and plays a pivotal role in the process of IS. Non-coding RNAs (ncRNAs), mainly contains microRNA, long non-coding RNA and circular RNA, have been extensively investigated on regulation of autophagy in human diseases. Recent studies have implied that ncRNAs-regulating autophagy participates in pathophysiological process of IS, including cell apoptosis, inflammation, oxidative stress, blood-brain barrier damage and glial activation, which indicates that regulating autophagy by ncRNAs may be beneficial for IS treatment. This review summarizes the role of autophagy in IS, as well as focuses on the role of ncRNAs-mediated autophagy in IS, for the development of potential therapeutic strategies in this disease.

Kidney impairment and outcomes in acute ischaemic stroke.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of stroke and mortality. AIMS: To evaluate the clinical and imaging features and outcomes of patients with and without kidney impairment among t admitted for acute ischaemic stroke (AIS). METHODS: AIS patients with brain magnetic resonance imaging (MRI) were included in the study. Kidney impairment was defined by an admission estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Cerebral microbleeds (CMB) and white matter hyperintensities (WMH) were evaluated using the Microbleed Anatomical Rating Scale and Fazekas scales, respectively. Primary outcomes were defined by modified Rankin Scale (mRS) and discharge disposition. Multivariate logistic regression analysis was performed to evaluate factors associated with the presence of kidney impairment and poor discharge outcomes. RESULTS: Of the 285 patients with AIS, 80 had kidney impairment on admission. Patients with kidney impairment were older (mean age ± standard deviation: 74.7 ± 12.9 vs 64.4 ± 13.8 years, P < 0.0001) and had more neurological deficits on National Institutes of Health Stroke Scale (NIHSS) score (median 8.5 vs 5, P = 0.02). In unadjusted analysis, patients with kidney impairment were less likely to have a good functional outcome (mRS 0-2: 36% vs 57%, P = 0.002) and good discharge outcome (home or inpatient rehabilitation: 68% vs 82%, P = 0.008). On multivariate analysis, kidney impairment was associated with higher NIHSS score (odds ratio (OR) = 1.04; 95% confidence interval (CI) = 1.002-1.08) and severe WMH (OR = 1.99; 95% CI = 1.06-3.77) suggestive of small vessel disease, but kidney impairment was not associated with poor discharge outcome (OR = 1.62; 95% CI = 0.75-3.53). CONCLUSION: Presence of kidney impairment at the time of stroke presentation, regardless of previous renal function, is associated with more neurological deficits and severe WMH on MRI.

Prenatal alcohol exposure exacerbates acute sensorimotor deficits and impedes long-term behavioral recovery from the effects of an adult-onset cerebrovascular ischemic stroke.

BACKGROUND: Prenatal alcohol exposure (PAE) is a significant risk factor for developmental disability, although its health consequences across the lifespan are poorly understood. Here, we hypothesized that latent brain and systemic consequences of PAE influence resiliency to adult-onset neurological disease, specifically, cerebrovascular ischemic stroke. METHODS: Pregnant Sprague-Dawley rats were exposed episodically to ethanol during the fetal neurogenic period. Adult (5 months) male and female PAE and control offspring were subjected to endothelin-1-induced unilateral middle cerebral artery occlusion. In the acute injury phase outcomes including stroke volume and neurological, endocrine, and gut permeability markers were assessed. Because the effects of stroke in human populations evolve over months to years, we also assessed hippocampal- and amygdala-dependent memory function and social interaction preference up to 6 months following a stroke, in middle-aged offspring. RESULTS: Prenatal alcohol exposure did not alter infarct volume, but significantly increased neurological deficits in both sexes, and impaired interhemispheric sensorimotor integration in PAE females. The IGF-1/IGFBP3 ratio, a measure of bioavailable IGF-1, was significantly reduced, while circulating levels of bacterial lipopolysaccharide, an inflammagen, were significantly increased in PAE males. In PAE females, the circulating IGF-1/IGFBP3 ratio was significantly increased and estradiol-17b levels were significantly reduced. The intestinal fatty acid binding protein, a surrogate marker of gut permeability was also significantly increased in PAE females. Longer-term deficits in hippocampal-associated memory and social interactions were observed in PAE males, while deficits in amygdala-dependent memory were observed in PAE females. CONCLUSIONS: PAE contributes to adverse effects on brain health and decreased resiliency in response to a common adult-onset neurovascular disease, cerebrovascular ischemic stroke.

Is the association of QTc with atrial fibrillation and stroke in cohort studies a matter of time?

OBJECTIVES: To investigate the association of the heart rate-corrected QT interval (QTc) with the risk of atrial fibrillation (AF) and ischaemic stroke. METHODS: We estimated the risk of AF and ischaemic stroke associated with QTc duration (ms) by Cox regression in study participants from the cohort of 60-year-old men and women from Stockholm (60YO) (n=4232). Univariate and multivariate adjusted risk estimates were expressed as HR and 95% CI. Main results were validated in elderly patients with AF, included in the Carebbean-e study, where an ECG in sinus rhythm (SR) (ECG-SR) recorded before the ECG diagnostic for (ECG-AF) was available (n=803). We estimated the correlation between the time interval (years) between the ECG-SR and ECG-AF with the QTc duration, by the Spearman correlation coefficient (rho). RESULTS: In the 60YO, the highest QTc duration quartile (>427 ms) associated with the AF risk (n=435) with a multivariable adjusted HR of 1.68 and 95% CI (1.26 to 2.24). No association was observed with ischaemic stroke. In the Carebbean-e study, no significant association was observed between the QTc duration measured on the ECG-SR and risk of ischaemic stroke during follow-up. QTc duration showed an inverse correlation (rho: -0.26, p<0.0001) with the time interval intercurred between ECG-SR and ECG-AF. CONCLUSIONS: The association of QTc duration with AF risk might depend on the time interval between the QTc measurement and the clinical diagnosis of AF. No association was observed between QTc duration and ischaemic stroke.

The Efficacy of Needle-Warming Moxibustion Combined with Hyperbaric Oxygen Therapy for Ischemic Stroke and Its Effect on Neurological Function.

OBJECTIVE: To elucidate the therapeutic efficacy of needle-warming moxibustion (NWM) combined with hyperbaric oxygen therapy (HBOT) in the treatment of patients with ischemic stroke and its effect on neurological function. METHODS: One hundred patients with ischemic stroke admitted to the Xuzhou Medical University Affiliated Hospital of Lianyungang from January 2019 to July 2021 were enrolled. Among them, 45 patients treated with NWM were set as the control group, and the rest 55 patients treated by NWM combined with HBOT were included in the research group. The curative effect, neurological deficit score, activity of daily living (ADL), balance ability, and the levels of serum proinflammatory factors in both groups were observed and recorded. Of them, the neurological deficit of patients was evaluated by the National Institutes of Health Stroke Scale (NHISS), the ADL ability was determined by the Barthel index score, and the balance ability was assessed by the Berg balance scale. RESULTS: The total effective rate of the research group was higher than that of the control group. Better ADL and balance ability and milder neurologic impairment were determined in the research group compared with the control group. After treatment, the secretion levels of proinflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) in the serum of patients in the research group were statistically lower than those before treatment and the control group. CONCLUSIONS: NWM combined with HBOT is effective in the treatment of patients with ischemic stroke, which can not only improve patients' neurological function, ADL, and balance ability but also inhibit serum inflammatory reactions.

Elevated Thyroid Autoantibodies Aggravate Stroke Severity in Euthyroidism with Acute Ischemic Stroke.

Introduction: Studies have indicated that immune reactions contribute to endothelial dysfunction and atherosclerosis. It is unclear whether thyroid dysfunction or elevated thyroid autoantibodies are associated with atherosclerosis. Therefore, we investigated the influence of thyroid autoimmunity related to elevated thyroid autoantibodies on functional outcome in euthyroidism with acute ischemic stroke (AIS). Methods: All patients with AIS underwent tests for thyroid function and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin autoantibody). We divided the patients suffering from euthyroidism and AIS into positive thyroid autoantibody and negative thyroid autoantibody groups. Demographic profiles, risk factors, and functional outcomes were compared between the two groups. Results: Out of the total 422 patients, 50 (11.8%) were included in the positive thyroid autoantibody group. The National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge was higher in the positive thyroid autoantibody group than the negative thyroid autoantibody group (P < 0.05). In addition, there was significant difference in the mortality during hospitalizations between the two groups (P < 0.01). Conclusion: This study showed that thyroid autoantibodies aggravate stroke severity in euthyroidism with AIS. We speculate that vascular damage related to thyroid autoimmunity may aggravate the increased risk of unfavorable outcomes, independent of thyroid function.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Frequency-Specific Changes of Amplitude of Low-Frequency Fluctuations in Patients with Acute Basal Ganglia Ischemic Stroke.

Objective: The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods: In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results: Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion: In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Dichotomous effects of autophagy on infarct volume in experimental permanent/transient ischemic stroke model: a systematic review and meta-analysis.

According to the recent findings, autophagy modulation is being a potential therapeutic target in the management of ischemic stroke in a pre-clinical setting. However, the pros and cons of autophagic response strongly depend on the activation time of autophagy after injury. In this systematic review, we aimed to explore the impacts of pharmacological modulation of autophagy on infarct size in experimental ischemic stroke models. Based on our preliminary search, 3551 publications were identified. Of twenty-nine publications that met the inclusion criteria, twenty studies reported infarct volume reduction by percentage (%) with no evidence of any publication bias while nine studies reported by mm3, which had publication bias (39.25 units, standardized mean differences (SMD) = 41.92, 95% confidence interval (CI): 30.33 to 53.51). Based on a meta-analysis, the point estimate (pooled mean difference) for improvement of infarct volume during autophagy modulation according to the mm3 and percentage were 35.64 (mean differences (MD) = 35.64, 95% CI: 26.43 to 44.85, z-value = 7.58, p-value < 0.001) and 14.38 (MD = 14.38, 95% CI = 10.50 to 18.26, z-value = 7.26, p < 0.001) units, respectively. Despite the undeniable role of autophagy in ischemic stroke, the dichotomous effects of autophagy regarding infarct volume reduction should be taken into account. Based on our findings, the studies included in this meta-analysis mostly reported a negative relation between autophagy induction and stroke volume development due to over-activity of autophagy upon the severe ischemic stroke; therefore, further pre-clinical studies are also recommended to establish adjusted autophagy with considering a time-dependent effect as a promising therapeutic target.

Dodging blood brain barrier with "nano" warriors: Novel strategy against ischemic stroke.

Ischemic stroke (IS) is one of the leading causes of death and disability resulting in inevitable burden globally. Ischemic injury initiates cascade of pathological events comprising energy dwindling, failure of ionic gradients, failure of blood brain barrier (BBB), vasogenic edema, calcium over accumulation, excitotoxicity, increased oxidative stress, mitochondrial dysfunction, inflammation and eventually cell death. In spite of such complexity of the disease, the only treatment approved by US Food and Drug Administration (FDA) is tissue plasminogen activator (t-PA). This therapy overcome blood deficiency in the brain along with side effects of reperfusion which are responsible for considerable tissue injury. Therefore, there is urgent need of novel therapeutic perspectives that can protect the integrity of BBB and salvageable brain tissue. Advancement in nanomedicine is empowering new approaches that are potent to improve the understanding and treatment of the IS. Herein, we focus nanomaterial mediated drug delivery systems (DDSs) and their role to bypass and cross BBB especially via intranasal drug delivery. The various nanocarriers used in DDSs are also discussed. In a nut shell, the objective is to provide an overview of use of nanomedicine in the diagnosis and treatment of IS to facilitate the research from benchtop to bedside.

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.

Choice of antithrombotic therapy for patients with atrial fibrillation undergoing carotid angioplasty and stenting: a nationwide population-based study.

Nonvalvular atrial fibrillation (NVAF) and carotid stenosis are important risk factors for stroke. Carotid angioplasty and stent placement (CAS) is recommended for patients with symptomatic high-grade carotid stenosis. The optimal medical management for patients with NVAF after CAS remains unclear. We aimed to clarify this issue using real-world data from the Taiwanese National Health Insurance Research Database (NHIRD). In total, 2116 consecutive NVAF patients who received CAS between January 1, 2010, and December 31, 2016, from NHIRD were divided into groups based on post-procedure medication as follows: only antiplatelet agent (OAP, n = 587); only anticoagulation agent (OAC, n = 477); dual antiplatelet agents (DAP, n = 49); and a combination of antiplatelet and anticoagulation agents (CAPAC, n = 304). Mortality, vascular events, and major bleeding episodes were compared after matching with the Charlson comorbidity index and CHA2DS2-VASc score. The CAPAC and the OAC groups had lower mortality rates than the OAP group (P = 0.0219), with no statistical differences in major bleeding, ischemic stroke, or vascular events. Conclusively, OAC therapy after CAS appears suitable for NVAF patients. CAPAC therapy might be considered as initial therapy or when there is concern about vascular events.

ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke.

Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2wt) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood-brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIPwt) and its phosphorylation-deficient mutant RKIPS153A, known inhibitors of the ERK1/2 signaling cascade. RKIPwt and RKIPS153A attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.

Middle Cerebral Artery Pulsatility Index Correlates with Prognosis and Diastolic Dysfunctions in Acute Ischemic Stroke.

OBJECTIVE: To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions. MATERIALS AND METHODS: Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated. RESULTS: We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI. CONCLUSIONS: High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.

Microvascular rarefaction in patients with cerebrovascular events.

Capillary density rarefaction and endothelial dysfunction contribute to chronic hypoperfusion and cerebral small vessel disease. Previous animal experiments revealed spatiotemporal microvascular remodeling directing post-stroke brain reorganization. We hypothesized that microcirculatory changes during acute cerebrovascular events could be reflected systemically and visualized sublingually. In a prospective observational trial in vivo sublingual sidestream darkfield videomicroscopy was performed in twenty-one patients with either acute stroke (n = 13 ischemic, n = 1 ischemic with hemorrhagic transformation and n = 2 hemorrhagic stroke) or transitory ischemic attacks (n = 5) within 24 h after hospital admission and compared to an age- and sex-matched control group. Repetitive measurements were performed on the third day and after one week. Functional and perfused total capillary density was rarefied in the overall patient group (3060 vs 3717 µm/mm2, p = 0.001 and 5263 vs 6550 µm/mm2, p = 0.002, respectively) and in patients with ischemic strokes (2897 vs. 3717 µm/mm2, p < 0.001 and 5263 vs. 6550 µm/mm2, p = 0.006, respectively) when compared to healthy controls. The perfused boundary region (PBR), which was measured as an inverse indicator of glycocalyx thickness, was markedly related to red blood cell (RBC) filling percentage (regarded as an estimate of microvessel perfusion) in the overall patient group (r = -0.843, p < 0.001), in patients with ischemic strokes (r = -0.82, p = 0.001) as well as in healthy volunteers (r = -0.845, p < 0.001). In addition, there were significant associations between platelet count or platelet aggregation values (as measured by whole blood impedance aggregometry) and microvascular parameters in the overall patient collective, as well as in patients with ischemic strokes. In conclusion, cerebrovascular events are associated with altered systemic microvascular perfusion.