High-frequency magnetic paired associated stimulation promotes motor function recovery in ischemic stroke patients: a study protocol for single-center, sham stimulation randomized controlled trials (H2MPAS).

BACKGROUND: Numerous studies have validated the clinical effectiveness of electromagnetic pairing-associated stimulation. Building upon this foundation, we have developed a novel approach involving high-frequency magnetic paired-associated stimulation, aiming to enhance clinical applicability and potentially improve efficacy. However, the clinical effectiveness of this approach remains unclear. Our objective is to demonstrate the therapeutic efficacy of this novel approach by employing high-frequency pairing to intervene in patients experiencing motor dysfunction following a stroke. METHODS: This is a single-center, single-blind, sham stimulation controlled clinical trial involving patients with upper limb motor dysfunction post-stroke. The intervention utilizes paired magnetic stimulation, combining peripheral and central magnetic stimulation, in patients with Brunnstrom stage III-V stroke lasting from 3 months to 1 year. Evaluation of patients' upper limb motor function occurred before the intervention and after 3 weeks of intervention. Follow-up visits will be conducted after 5 weeks and 3 months of intervention. The primary outcome measure is the Action Research Arm Test, with secondary measures including the Fugl-Meyer Assessment-upper, Modified Barthel Index, modified Tardieu scale, functional near-infrared spectroscopy, and neuroelectrophysiology. DISCUSSION: The high-frequency magnetic paired associative stimulation used in this study combined high-frequency magnetic stimulation with paired stimulation, potentially facilitating both cortical excitation through high-frequency stimulation and specific circuit enhancement through paired stimulation. As dual-coil magnetic stimulation equipment becomes increasingly popular, magnetic-magnetic paired associated stimulation may offer patients improved clinical outcomes at reduced costs. TRIAL REGISTRATION: Chinese Clinical Trial Registry,ChiCTR2400083363. Registered on 23 April 2024.

The Blood-Cerebrospinal Fluid Barrier Dysfunction in Brain Disorders and Stroke: Why, How, What For?

Ischemic stroke (IS) results in the interruption of blood flow to the brain, which can cause significant damage. The pathophysiological mechanisms of IS include ionic imbalances, oxidative stress, neuroinflammation, and impairment of brain barriers. Brain barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (B-CSF), protect the brain from harmful substances by regulating the neurochemical environment. Although the BBB is widely recognized for its crucial role in protecting the brain and its involvement in conditions such as stroke, the B-CSF requires further study. The B-CSF plays a fundamental role in regulating the CSF environment and maintaining the homeostasis of the central nervous system (CNS). However, the impact of B-CSF impairment during pathological events such as IS is not yet fully understood. In conditions like IS and other neurological disorders, the B-CSF can become compromised, allowing the entry of inflammatory substances and increasing neuronal damage. Understanding and preserving the integrity of the B-CSF are crucial for mitigating damage and facilitating recovery after ischemic stroke, highlighting its fundamental role in regulating the CNS during adverse neurological conditions.

Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study.

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

In vitro modelling of the neurovascular unit for ischemic stroke research: Emphasis on human cell applications and 3D model design.

Ischemic stroke has garnered global medical attention as one of the most serious cerebrovascular diseases. The mechanisms involved in both the development and recovery phases of ischemic stroke are complex, involving intricate interactions among different types of cells, each with its own unique functions. To better understand the possible pathogenesis, neurovascular unit (NVU), a concept comprising neurons, endothelial cells, mural cells, glial cells, and extracellular matrix components, has been used in analysing various brain diseases, particularly in ischemic stroke, aiming to depict the interactions between cerebral vasculature and neural cells. While in vivo models often face limitations in terms of reproducibility and the ability to precisely mimic human pathophysiology, it is now important to establish in vitro NVU models for ischemic stroke research. In order to accurately portray the pathological processes occurring within the brain, a diverse array of NVU 2D and 3D in vitro models, each possessing unique characteristics and advantages, have been meticulously developed. This review presents a comprehensive overview of recent advancements in in vitro models specifically tailored for investigating ischemic stroke. Through a systematic categorization of these developments, we elucidate the intricate links between NVU components and the pathogenesis of ischemic stroke. Furthermore, we explore the distinct advantages offered by innovative NVU models, notably 3D models, which closely emulate in vivo conditions. Additionally, an examination of current therapeutic modalities for ischemic stroke developed utilizing in vitro NVU models is provided. Serving as a valuable reference, this review aids in the design and implementation of effective in vitro models for ischemic stroke research.

Normobaric Hyperoxia Combined with Endovascular Treatment in Patients with Acute Ischemic Stroke (OPENS-2) Trial: Protocol for a Prospective, Multicenter, Randomized Controlled Study.

Normobaric hyperoxia (NBO) is a potentially promising stroke treatment strategy that could protect the ischemic penumbra and could be administered as an adjunct before vascular recanalization. However, the efficacy and safety of NBO have not been confirmed by randomized controlled trials. The study aims to assess the efficacy and safety of NBO for ischemic stroke due to large artery occlusion (LVO) of acute anterior circulation among patients who had endovascular treatment (EVT) and were randomized within 6 h from symptom onset. Based on the data of the modified Rankin Scale (mRS) score at 90 days from the normobaric hyperoxia combined with EVT for acute ischemic stroke (OPENS: NCT03620370) trial, 284 patients will be included to achieve a 90% power by using Wilcoxon-Mann-Whitney test and the proportional odds model to calculate the sample size. The study is a prospective, multicenter, blinded, randomized controlled trial. The NBO group is administered with mask oxygen therapy of 10 L/min, while the sham NBO group is with that of 1 L/min. The primary outcome is the mRS score at 90 days. Secondary endpoints include cerebral infarct volume at 24-48 h, functional independence (mRS ≤2) at 90 days, and improvement in neurological function at 24 h. Safety outcomes include 90-day mortality, oxygen-related adverse events, and serious adverse events. This study will indicate whether NBO combined with EVT is superior to EVT alone for acute ischemic stroke caused by LVO in subjects randomized within 6 h from symptom onset and will provide some evidence for NBO intervention as an adjunct to thrombectomy for acute stroke.

Effects of intracranial artery stenosis of anterior circulation on cognition-A CT perfusion-based study.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. METHODS: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-Tmax. The correlations between cognitive function and abnormal perfusion were explored. RESULTS: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. CONCLUSION: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI.

Predictive value of early serum ACSL4 and ASITN/SIR grade for motor function recovery in patients with post-ischemic stroke lower limb neurological sequelae after modified constraint-induced movement therapy.

BACKGROUND: Ischemic stroke accounts for over 85 % of all stroke types. Acyl-CoA synthetase long chain family member 4 (ACSL4) is considered to promote myocardial and cerebral ischaemia/ reperfusion. However, up to now, no study focused on the role of ACSL4 in patients with post-stroke lower limb neurological sequelae. OBJECTIVE: The present study aimed to investigate the predictive value of ACSL4 and collateral circulation for lower limb neurological sequelae of ischemic stroke patients after modified constraint-induced movement therapy (mCIMT). METHODS: This is a prospective cohort study which included 99 ischemic stroke patients with lower limb neurological sequelae who were admitted to our hospital during January 2021 to December 2022. All patients received mCIMT after the admission. Collateral circulation was evaluated by digital subtraction angiography (DSA) and graded by the American Society of Interventional and Therapeutic Neuroradiology/ Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme linked immunosorbent assay (ELISA) was used to detect serum ACSL4. Basic characteristics were collected and lower limb motor function was measured by Fugl-Meyer score (FMS), modified Ashworth score (MAS) and Brunnstrom stage, as well as timed up and go (TUG) test, ten-Meter walk test (10MWT), and six-minute walk test (6MWT) before and after treatment. RESULTS: Serum ACSL4 and percentage of patients with ASITN/SIR 0-1 decreased significantly after treatment compared with the values before treatment. Patients with higher baseline serum ACSL4 values at admission showed significantly lower FMS scores, higher TUG and 10MWT, as well as lower 6MWT. Patients with ASITN/SIR grade 0-1 at admission only showed significantly higher TUG and 10MWT, as well as lower 6MWT. Receiver operating characteristic (ROC) curves showed ACSL4 and ASITN/SIR grade could be used to predict the prognosis. Logistic regression found only national institutes of health stroke scores (NIHSS) was the independent risk factor for post-treatment motor impairment after mCIMT. CONCLUSION: Higher levels of ACSL4 and ASITN/SIR 0-1 are associated with poor recovery of motor functions of patients with post-stroke sequelae after mCIMT.

Assessment of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging in Ischemic Stroke Patients Without Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. METHODS AND RESULTS: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P<0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P<0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P=0.35). CONCLUSIONS: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.

Exploring the Impact of Age and Pre-Stroke Modified Rankin Scale in Elderly Thrombectomy: A 15-Year Single-Center Experience.

INTRODUCTION: The selection of endovascular thrombectomy (EVT) for acute ischemic stroke in the elderly remains challenging due to the underrepresentation of these patients in landmark randomized trials. The aim of this study was to assess the association between age and the pre-stroke modified Rankin scale score with functional outcomes after EVT in elderly patients aged ≥80 years. METHODS: We prospectively collected data from consecutive elderly patients who underwent EVT of the anterior or posterior circulation at our institution between 2007 and 2022. Clinical and radiological parameters were analyzed using a fair outcome (mRS ≤3 or retained pre-stroke mRS score of 4) as the primary outcome. RESULTS: In total, 307 elderly patients were included in the analysis. Fair functional outcomes were achieved in 162 (53%) patients. Eighty-four (27.4%) patients were deceased at 3-month follow-up and the mortality rate increased to 37.1% (114 deceased) at 1-year follow-up. The likelihood of achieving a fair functional outcome decreased by 8% for every 1-year age increase (OR 0.81, 95% CI 0.73-0.90). Lower National Institutes of Health Stroke Scale (OR 0.89, 95% CI 0.85-0.93, p < 0.001) and pre-stroke mRS (OR 0.67, 95% CI 0.53-0.84, p < 0.001) were associated with fair outcomes. CONCLUSIONS: EVT in elderly patients with stroke is beneficial in selected cases. Increasing age was associated with an increased risk of an mRS change to 4 or worse and death within 1 year. The pre-stroke mRS may aid clinicians in the selection of elderly patients for EVT.

A hyper-viscoelastic uniaxial characterization of collagenous embolus analogs in acute ischemic stroke.

PURPOSE: Acute ischemic stroke is a leading cause of death and morbidity worldwide. Despite advances in medical technology, nearly 30% of strokes result in incomplete vessel recanalization. Recent studies have demonstrated that clot composition correlates with success rates of mechanical thrombectomy procedures. To understand clot behavior during thrombectomy, which exerts considerable strains on thrombi, in vitro studies must characterize the rate-dependent high-strain behavior of embolus analogs (EAs) with different formation conditions, which can be used to fit models of hyper-viscoelasticity. METHODS: In this study, the effect of collagen infiltration as a carotid-induced collagen-rich thrombosis surrogate is considered as a contributor to embolus analog high-strain stiffness, when compared to 40% hematocrit EAs. RESULTS: EA high-strain stiffnesses, characterized on a uniaxial load frame, increase by an order of magnitude for collagenous clot analogs. Chandler loop analogs show high-strain stiffnesses and clot compositions commensurate with previous reports of stroke patient clots, and collagenous clots show significant increase in stiffness when compared to stroke patient clots. Finally, hyper-viscoelastic curve fitting demonstrates the asymmetry between tension and compression. Nonlinear, rate-dependent models that consider clot-stiffening behavior match the high strain stiffness of clots fairly well. Furthermore, we demonstrate that the stability of the elastic energy needs to be considered to obtain optimal curve fits for high-strain, rate dependent data. CONCLUSION: This study provides a framework for the development of dynamically formed EAs that mimic the mechanical and structural properties of in vivo clots and provides parameters for numerical simulation of clot behavior with hyper-viscoelastic models.

Heart rate variability biofeedback enhances cognitive, motor, psychological, and autonomic functions in post-stroke rehabilitation.

Post-stroke patients often experience psychological distress and autonomic nervous system (ANS) dysregulation, impacting their well-being. This study evaluated the effectiveness of heart rate variability (HRV) biofeedback on cognitive, motor, psychological, and ANS functions in sixty-two ischemic stroke patients (43 males, mean age = 60.1) at a Medical Center in southern Taiwan. To prevent interaction, we allocated patients to the HRV biofeedback or control (usual care) group based on their assigned rehabilitation days, with 31 patients in each group. Assessments conducted at baseline, three, and six months included the Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment for Upper Extremities (FMA-UE), Perceived Stress Scale, Hospital Anxiety and Depression Scales (HADS), and HRV indices. Mixed-effect models were used to analyze Group by Time interactions. The results revealed significant interactions across all functions. At 3 months, significant improvements in the HRV biofeedback group were observed only in MoCA, FMA-UE, and HADS-depression scores compared to the control group. By 6 months, all measured outcomes demonstrated significant improvements in the biofeedback group relative to the control group. These results suggest that HRV biofeedback may be an effective complementary intervention in post-stroke rehabilitation, warranting further validation.

Systematic Druggable Genome-Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke.

BACKGROUND: Stroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke . METHODS AND RESULTS: Cis-expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3-6 versus 0-2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome-wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes (ABCC2, ATRAID, BLK, CD93, CHST13, NR1H3, NRBP1, PI3, RIPK4, SEMG1, SLC22A4, SLC22A5, SLCO3A1, TEK, TLR4, and WNT10B) demonstrated the causal associations with ordinal modified Rankin Scale (P<1.892×10-5) or poor functional outcome (modified Rankin Scale 3-6 versus 0-2, P<1.893×10-5). Steiger filtering analysis suggested potential directional stability (P<0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2, NRBP1, PI3, and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome-wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2, NRBP1, PI3, and SEMG1, but the robustness of these results was limited by low power. CONCLUSIONS: The present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

Relative Cerebral Blood Flow as an Indirect Imaging Surrogate in Patients With Anterior Circulation Large Vessel Occlusion and Association of Baseline Characteristics With Poor Collateral Status.

BACKGROUND: In acute ischemic stroke (AIS), collateral status (CS) is an important predictor of favorable outcomes in patients with AIS. Among quantitative cerebral perfusion parameters, relative cerebral blood flow (rCBF) is considered an accurate perfusion-based indicator of CS. This study investigated the relationship between admission laboratory values, baseline characteristics, and CS as assessed by rCBF in patients with AIS-large vessel occlusion. METHODS AND RESULTS: In this retrospective multicenter study, consecutive patients presenting with AIS secondary to anterior circulation large vessel occlusion who underwent pretreatment computed tomography perfusion were included. The computed tomography perfusion data processed by RAPID (IschemaView, Menlo Park, CA) generated the rCBF. Binary logistic regression models assessed the relationship between patients' baseline characteristics, admission laboratory values, and poor CS. The primary outcome measure was the presence of poor CS, which was defined as rCBF <38% at a lesion size ≥27 mL. Between January 2017 and September 2022, there were 221 consecutive patients with AIS-large vessel occlusion included in our study (mean age 67.0±15.8 years, 119 men [53.8%]). Logistic regression showed that male sex (odds ratio [OR], 2.98 [1.59-5.59]; P=0.001), chronic kidney disease (OR, 5.18 [2.44-11.0]; P<0.001), admission National Institutes of Health Stroke Scale score ≥12 (OR, 5.17 [2.36-11.36]; P<0.001), and systolic blood pressure <140 (OR, 2.00 [1.07-3.76]; P=0.030) were associated with poor CS. CONCLUSIONS: Higher stroke severity on admission with National Institutes of Health Stroke Scale score ≥12, systolic blood pressure <140, chronic kidney disease, and male sex are statistically significantly associated with poor CS in patients with AIS due to anterior circulation large vessel occlusion as defined by rCBF <38%.

Hypoperfusion Intensity Ratio as an Indirect Imaging Surrogate in Patients With Anterior Circulation Large-Vessel Occlusion and Association of Baseline Characteristics With Poor Collateral Status.

BACKGROUND: Collateral status (CS) plays a crucial role in infarct growth rate, risk of postthrombectomy hemorrhage, and overall clinical outcomes in patients with acute ischemic stroke (AIS) secondary to anterior circulation large-vessel occlusions (LVOs). Hypoperfusion intensity ratio has been previously validated as an indirect noninvasive pretreatment imaging biomarker of CS. In addition to imaging, derangements in admission laboratory findings can also influence outcomes in patients with AIS-LVO. Therefore, our study aims to assess the relationship between admission laboratory findings, baseline characteristics, and CS, as assessed by hypoperfusion intensity ratio in patients with AIS-LVO. METHODS AND RESULTS: In this retrospective study, consecutive patients presenting with AIS secondary to anterior circulation LVO who underwent pretreatment computed tomography perfusion were included. The computed tomography perfusion data processed by RAPID (Ischema View, Menlo Park, CA) generated the hypoperfusion intensity ratio. Binary logistic regression models were used to assess the relationship between patients' baseline characteristics, admission laboratory findings, and poor CS. A total of 221 consecutive patients with AIS-LVO between January 2017 and September 2022 were included in our study (mean±SD age, 67.0±15.8 years; 119 men [53.8%]). Multivariable logistic regression showed that patients with AIS caused by cardioembolic and cryptogenic causes (adjusted odds ratio [OR], 2.67; 95% CI, 1.20-5.97; P=0.016), those who presented with admission National Institutes of Health Stroke Scale score ≥12 (adjusted OR, 3.12; 95% CI, 1.61-6.04; P=0.001), and male patients (adjusted OR, 2.06; 95% CI, 1.13-3.77; P=0.018) were associated with poor CS. CONCLUSIONS: Stroke caused by cardioembolic or cryptogenic causes, admission National Institutes of Health Stroke Scale score of ≥12, and male sex were associated with poor CS, as defined by hypoperfusion intensity ratio in the patients with AIS-LVO.

High relative cerebral blood volume is associated with good long term clinical outcomes in acute ischemic stroke: a retrospective cohort study.

BACKGROUND: Endovascular therapy for acute ischemic stroke has been shown to be highly effective in selected patients. However, the ideal criteria for patient selection are still debated. It is well known that collateral flow is an important factor, but the assessment is often subjective and time-consuming. Relative cerebral blood volume (rCBV) is a putative indicator of collateral capacity and can be quickly and easily determined by automated quantitative analysis. We investigated the relationship between rCBV of the affected region and clinical outcome in patients with acute ischemic stroke after endovascular therapy. METHODS: We conducted a retrospective study on consecutive patients between January 2017 and May 2019. Patients with acute ischemic stroke of the anterior circulation who underwent imaging including computed tomography perfusion and were treated with mechanical thrombectomy (MT) were eligible for inclusion. rCBV was calculated automatically with RAPID software by dividing the average cerebral blood volume (CBV) of the affected region (time-to-maximum (Tmax) > 6 s) by the CBV of the unaffected contralateral side. The primary outcome was determined by the modified Rankin Scale (mRS) after 90 days. Good clinical outcome was defined as mRS ≤ 2. We compared means, performed mono- and multivariate logistical regression and calculated a receiver operating characteristic (ROC)-analysis to determine the ideal cutoff value to predict clinical outcomes. RESULTS: 155 patients were enrolled in this study. 66 patients (42.58%) had good clinical outcomes. Higher rCBV was associated with good clinical outcome (p < 0.001), even after adjustment for the patients' status according to mRS and National Institute of Health Stroke Scale (NIHSS) age and Alberta stroke program early computed tomography score (ASPECTS) at baseline (p = 0.006). ROC-analysis revealed 0.650 (confidence interval: 0.616-0.778) as the optimal cutoff value. CONCLUSION: Higher rCBV at baseline is associated with good clinical long-term outcomes in patients with acute ischemic stroke treated by MT. In this study we provide the biggest collective so far that gives evidence that rCBV can be a valuable tool to identify patients who might benefit from MT and are able give a threshold to help to offer patients MT in borderline cases.

Short-chain fatty acid on blood-brain barrier and glial function in ischemic stroke.

Stroke is the second most common cause of death and one of the most common causes of disability worldwide. The intestine is home to several microorganisms that fulfill essential functions for the natural and physiological functioning of the human body. There is an interaction between the central nervous system (CNS) and the gastrointestinal system that enables bidirectional communication between them, the so-called gut-brain axis. Based on the gut-brain axis, there is evidence of a link between the gut microbiota and the regulation of microglial functions through glial activation. This interaction is partly due to the immunological properties of the microbiota and its connection with the CNS, such that metabolites produced by the microbiota can cross the gut barrier, enter the bloodstream and reach the CNS and significantly affect microglia, astrocytes and other cells of the immune system. Studies addressing the effects of short-chain fatty acids (SCFAs) on glial function and the BBB in ischemic stroke are still scarce. Therefore, this review aims to stimulate the investigation of these associations, as well as to generate new studies on this topic that can clarify the role of SCFAs after stroke in a more robust manner.

Evaluating the interaction between hemorrhagic transformation and cerebral edema on functional outcome after ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. CONCLUSIONS: Most stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.

[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 between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

INTRODUCTION: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. METHODS: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. RESULTS: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). CONCLUSION: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.