Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

The protective role of endothelial GLUT1 in ischemic stroke.

OBJECTIVE: To provide thorough insight on the protective role of endothelial glucose transporter 1 (GLUT1) in ischemic stroke. METHODS: We comprehensively review the role of endothelial GLUT1 in ischemic stroke by narrating the findings concerning biological characteristics of GLUT1 in brain in depth, summarizing the changes of endothelial GLUT1 expression and activity during ischemic stroke, discussing how GLUT1 achieves its neuroprotective effect via maintaining endothelial function, and identifying some outstanding blind spots in current studies. RESULTS: Endothelial GLUT1 maintains persistent high glucose and energy requirements of the brain by transporting glucose through the blood-brain barrier, which preserves endothelial function and is beneficial to stroke prognosis. CONCLUSION: This review underscores the potential involvement of GLUT1 trafficking, activity modulation, and degradation, and we look forward to more clinical and animal studies to illuminate these mechanisms.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Presentation: A Population Study.

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Collaterals and stroke reperfusion: Too few leads to too much.

Adequate reperfusion after ischemic stroke is a major determinant of functional outcome yet remains unpredictable and insufficient for most survivors. In this issue of Neuron, Binder et al.1 identify leptomeningeal collaterals (LMCs) in mice and human patients as a key factor in regulating reperfusion and hemorrhagic transformation following stroke.

Increased sensitivity in detection of deficits following two commonly used animal models of stroke.

Stroke is a leading cause of death and disability in the United States. Most strokes are ischemic, resulting in both cognitive and motor impairments. Animal models of ischemic stroke such as the distal middle cerebral artery occlusion (dMCAO) and photothrombotic stroke (PTS) procedures have become invaluable tools, with their own advantages and disadvantages. The dMCAO model is clinically relevant as it occludes the artery most affected in humans, but yields variability in the infarct location as well as the behavioral and cognitive phenotypes disrupted. The PTS model has the advantage of allowing for targeted location of infarct, but is less clinically relevant. The present study evaluates phenotype disruption over time in mice subjected to either dMCAO, PTS, or a sham surgery. Post-surgery, animals were tested over 28 days on standard motor tasks (grid walk, cylinder, tapered beam, and rotating beam), as well as a novel odor-based operant task; the 5:1 Odor Discrimination Task (ODT). Results demonstrate a significantly greater disturbance of motor control with PTS as compared with Sham and dMCAO. Disruption of the PTS group was detected up to 28 days post-stroke on the grid walk, and up to 7 days on the rotating and tapered beam tasks. PTS also led to significant short-term disruption of ODT performance (1-day post-surgery), exclusively in males, which appeared to be driven by motoric disruption of the lick response. Together, this data provides critical insights into the selection and optimization of animal models for ischemic stroke research. Notably, the PTS procedure was best suited for producing disruptions of motor behavior that can be detected with common behavioral assays and are relatively enduring, as is observed in human stroke.

Abnormal degree centrality as a potential imaging biomarker for ischemic stroke: A resting-state functional magnetic resonance imaging study.

OBJECTIVE: To explore degree centrality (DC) abnormalities in ischemic stroke patients and determine whether these abnormalities have potential value in understanding the pathological mechanisms of ischemic stroke patients. METHODS: Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were subjected to DC analysis. Then we conducted a correlation analysis between DC values and neuropsychological test scores, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Finally, extracted the abnormal DC values of brain regions and defined them as features for support vector machine (SVM) analysis. RESULTS: Compared with HCs, ischemic stroke patients showed increased DC in the bilateral supplementary motor area, and median cingulate and paracingulate gyri and decreased DC in the left postcentral gyrus, right calcarine fissure and surrounding cortex, lingual gyrus, and orbital parts of the right superior frontal gyrus and bilateral cuneus. Correlation analyses revealed that DC values in the right lingual gyrus, calcarine fissure and surrounding cortex, and orbital parts of the right superior frontal gyrus were positively correlated with the MMSE scores. The SVM classification of the DC values achieved an area under the curve (AUC) of 0.93, an accuracy of 89.47%. CONCLUSION: Our research results indicate that ischemic stroke patients exhibit abnormalities in the global connectivity mechanisms and patterns of the brain network. These abnormal changes may provide neuroimaging evidence for stroke-related motor, visual, and cognitive impairments, contribute to a deeper comprehension of the underlying pathophysiological mechanisms implicated in ischemic stroke.

Thrombolysis treatment protected impairment of functional ability, quality of life and fatigue seven years after stroke.

OBJECTIVES: We studied quality of life, functional outcome, depression, and fatigue of ischemic stroke patients treated with or without thrombolysis seven years post-stroke. MATERIALS AND METHODS: A total of 204 ischemic stroke patients treated with or without thrombolysis during 2013-2015. After seven years the 136 survivors were assessed with telephone interview, which included questions about subjective quality of life (European Quality of Life-5 Dimensions), depression, fatigue with Fatigue Severity Scale, functional ability assessed with Barthel Index and Modified Rankin Scale, living conditions, need of care, and medical aids. RESULTS: At admission patients with thrombolysis had higher National Institutes of Health Stroke Scale scores compared with those not treated with thrombolysis. At seven years post-stroke, 99% of alive patients answered the questionnaires. There were no group differences concerning functional outcome, quality of life, depression, fatigue, or insomnia. The Barthel Index was normal in both groups. The quality of life was good in both groups without group differences in any domains. Of all patients, 68% reported no problems in usual activities, and 61% were without pain. Anxiety or depression were experienced by 19% of all stroke patients, while fatigue was present in 32% of cases. CONCLUSIONS: Seven years post-stroke the quality of life was good and functional outcome remained in good level in both study groups. One third experienced fatigue, while every fifth experienced depression. The thrombolysis treatment seems to protect from decreased quality of life, fatigue, and decreased mobility, self-care, and usual activities despite more severe stroke.

Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.

Inhibition of Notch1 signal promotes brain recovery by modulating glial activity after stroke.

BACKGROUND: Notch1 signaling inhibiton with N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester] (DAPT) treatment could promote brain recovery and the intervention effect is different between striatum (STR) and cortex (CTX), which might be accounted for different changes of glial activities, but the in-depth mechanism is still unknown. The purpose of this study was to identify whether DAPT could modulate microglial subtype shifts and astroglial-endfeet aquaporin-4 (AQP4) mediated waste solute drainage. METHODS: Sprague-Dawley rats (n=10) were subjected to 90min of middle cerebral artery occlusion (MCAO) and were treated with DAPT (n=5) or act as control with no treatment (n=5). Two groups of rats underwent MRI scans at 24h and 4 week, and sacrificed at 4 week after stroke for immunofluorescence (IF). RESULTS: Compared with control rats, MRI data showed structural recovery in ipsilateral STR but not CTX. And IF showed decreased pro-inflammatory M1 microglia and increased anti-inflammatory M2 microglia in striatal lesion core and peri-lesions of STR, CTX. Meanwhile, IF showed decreased AQP4 polarity in ischemic brain tissue, however, AQP4 polarity in striatal peri-lesions of DAPT treated rats was higher than that in control rats but shows no difference in cortical peri-lesions between control and treated rats. CONCLUSIONS: The present study indicated that DAPT could promote protective microglia subtype shift and striatal astrocyte mediated waste solute drainage, that the later might be the major contributor of waste solute metabolism and one of the accounts for discrepant recovery of STR and CTX.

Differentiating ischemic stroke patients from healthy subjects using a large-scale, retrospective EEG database and machine learning methods.

OBJECTIVES: We set out to develop a machine learning model capable of distinguishing patients presenting with ischemic stroke from a healthy cohort of subjects. The model relies on a 3-min resting electroencephalogram (EEG) recording from which features can be computed. MATERIALS AND METHODS: Using a large-scale, retrospective database of EEG recordings and matching clinical reports, we were able to construct a dataset of 1385 healthy subjects and 374 stroke patients. With subjects often producing more than one recording per session, the final dataset consisted of 2401 EEG recordings (63% healthy, 37% stroke). RESULTS: Using a rich set of features encompassing both the spectral and temporal domains, our model yielded an AUC of 0.95, with a sensitivity and specificity of 93% and 86%, respectively. Allowing for multiple recordings per subject in the training set boosted sensitivity by 7%, attributable to a more balanced dataset. CONCLUSIONS: Our work demonstrates strong potential for the use of EEG in conjunction with machine learning methods to distinguish stroke patients from healthy subjects. Our approach provides a solution that is not only timely (3-minutes recording time) but also highly precise and accurate (AUC: 0.95).

Multi-Task Heterogeneous Ensemble Learning-Based Cross-Subject EEG Classification Under Stroke Patients.

Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.

The role of dorsolateral striatum in the effects of deep cerebellar stimulation-mediated motor recovery following ischemic stroke in rodents.

Despite great advances in acute care and rehabilitation, stroke remains the leading cause of motor impairment in the industrialized world. We have developed a deep brain stimulation (DBS)-based approach for post-stroke rehabilitation that has shown reproducible effects in rodent models and has been recently translated to humans. Mechanisms underlying the rehabilitative effects of this novel therapy have been largely focused on the ipsilesional cortex, including cortical reorganization, synaptogenesis, neurogenesis and greater expression of markers of long-term potentiation. The role of subcortical structures on its therapeutic benefits, particularly the striatum, remain unclear. In this study, we compared the motor rehabilitative effects of deep cerebellar stimulation in two rodent models of cerebral ischemia: a) cortical ischemia; and b) combined striatal and cortical ischemia. All animals underwent the same procedures, including implantation of the electrodes and tethered connections for stimulation. Both experimental groups received four weeks of continuous lateral cerebellar nucleus (LCN) DBS and each was paired with a no stimulation, sham, group. Fine motor function was indexed using the pasta matrix task. Brain tissue was harvested for histology and immunohistochemical analyses. In the cortical-only ischemia, the average pasta matrix performance of both sham and stimulated groups reduced from 19 to 24 pieces to 7-8 pieces following the stroke induction. At the end of the four-week treatment, the performance of stimulated group was significantly greater than that of sham group (14 pieces vs 7 pieces, p < 0.0001). Similarly, in the combined cortical and striatal ischemia, the performance of both sham and stimulated groups reduced from 29 to 30 pieces to 7-11 pieces following the stroke induction. However, at the end of the four-week treatment, the performance of stimulated group was not significantly greater than that of sham group (15 pieces vs 11 pieces, p = 0.452). In the post-mortem analysis, the number of cells expressing CaMKIIα at the perilesional cortical and striatum of the LCN DBS treated animals receiving cortical-only stroke elevated but not those receiving cortical+striatal stroke. The current findings suggested that the observed, LCN DBS-enhanced motor recovery and perilesional plasticity may involve striatal mechanisms.

Procedural blood pressure and contrast extravasation on dual energy computed tomography after endovascular stroke treatment.

BACKGROUND: Blood brain barrier disruption (BBBD) can be visualized by contrast extravasation (CE) after endovascular treatment (EVT) in patients with acute ischemic stroke. Elevated blood pressure is a risk factor for BBBD. However, the association between procedural blood pressure and CE post-EVT is unknown. METHODS: In this single-center retrospective study, we analyzed 501 eligible patients who received a dual energy CT (DECT) immediately post-EVT for acute ischemic stroke. Procedural blood pressure values (SBPmean, SBPmax, SBPmax-min, and MAPmean) were collected. CE was quantified by measuring the maximum parenchymal iodine concentration on DECT iodine overlay map reconstructions. As a measure for the extent of BBBD, we created CE-ASPECTS by deducting one point per hyperdense ASPECTS region on iodine overlay maps. The association between blood pressure and CE was assessed using multivariable linear regression. RESULTS: The procedural SBPmean, SBPmax, and MAPmean were 150 ± 26 mmHg, 173 ± 29 mmHg, and 101 ± 17 mmHg, respectively. The median maximum iodine concentration on post-EVT DECT was 1.2 mg/ml (IQR 0.7-2.0), and median CE-ASPECTS was 8 (IQR 5-11). The maximum iodine concentration was not associated with blood pressure. SBPmean, SBPmax, and MAPmean were significantly associated with CE-ASPECTS (per 10 mmHg, ß = -0.2, 95 % CI -0.31 to -0.09, ß = -0.15, 95 % CI -0.25 to -0.06, ß = -0.33, 95 % CI -0.49 to -0.17, respectively). CONCLUSION: In acute ischemic stroke patients undergoing EVT, particularly in patients achieving successful recanalization, SBPmean, SBPmax, and MAPmean are associated with the extent of BBBD on immediate post-EVT DECT, but not with maximum iodine concentration.

Assessing left atrial size and pump function in ischemic stroke patients: Is cardiac MRI superior to transthoracic echocardiography?

OBJECTIVES: Current guidelines recommend transthoracic echocardiography (TTE) following an ischemic stroke as the primary technique to identify cardiac abnormalities associated with an increased risk of cerebral embolism. It is unclear whether cardiac magnetic resonance imaging (cMRI), a technique shown to provide increased imaging resolution, may also enhance the cardiac assessment of ischemic stroke patients. We compared cMRI with TTE in the evaluation of Left Atrial (LA) size and pump function in a cohort of 44 patients with ischemic stroke. MATERIALS AND METHODS: The biplane method was utilized to acquire LA diameters as well as area measurements in both TTE and cMRI. We calculated LA volume (LAV), LAV index (LAVI), LA Global Longitudinal Strain (GLS) and LA pump function. Results were compared using paired two sample for means t-test. Lin's concordance correlation coefficient (CCC) and Bland-Altman methods quantified the agreement of measurements obtained by TTE and cMRI. RESULTS: LAVI measurements by cMRI were significantly larger (34.97 v. 28.81; p = 0.001) than by TTE. The concordance correlation demonstrated only a weak agreement between LA size measured by cMRI and TTE (ρc = 0.397; p= 0.001, 95% CI 0.16 - 0.59), and the Bland-Altman plot demonstrated that LAVI measured by cMRI averaged 6.3 ml/m2 larger magnitude than those obtained by TTE. CONCLUSIONS: Using TTE alone leads to an underestimation of LA abnormalities important in the evaluation of ischemic stroke patients. Nearly one in every five ischemic stroke patients evaluated based on the current guidelines may have a missed potential source of cardiac embolism.

Status Epilepticus after mechanical thrombectomy: The role of early EEG assessment in Stroke Unit, clinical and radiological prognostication.

BACKGROUND: Convulsive (CSE) and non-convulsive (NCSE) Status Epilepticus are a complication in 0.2-0.3% ischemic strokes. Large stroke and cortical involvement are the main risk factors for developing SE. This study evaluates the prevalence of SE in patients treated with endovascular thrombectomy (EVT) through EEG recording within 72- h from admission. Moreover, we compared clinical, radiological, and outcome measures in SE and no-SE patients. MATERIALS AND METHODS: We collected retrospectively demographical and clinical characteristics of acute ischemic stroke patients who underwent EVT, admitted in the Stroke Unit (SU) of the University Hospital of Trieste between January 2018 and March 2020 who underwent EEG recording within 72- h from the symptoms' onset. RESULTS: Out of 247 EVT patients, 138 met the inclusion criteria, of whom 9 (6.5%) showed SE with median onset time of 1 day (IQR 1-2). No difference was found between the two groups as for age, sex, risk factors, grade of recanalization, etiology of stroke, and closed vessel. The no-SE group presented higher NIHSS improvement rate (p=0.025) compared to the SE group. The sum of the lobes involved in the ischemic lesion was significantly higher in SE group (p=0.048). CONCLUSION: SE after EVT in large strokes is a non-rare complication, with most being NCSE. Performing a rapid EEG assessment in a Stroke Unit setting may allow for a prompt recognition and treatment of SE in the acute/hyper-acute phase. SE may be correlated with worse clinical outcomes in patients with large vessel occlusion.

Ignored Role of Paroxysmal Atrial Fibrillation in the Pathophysiology of Cryptogenic Stroke in Patients with Patent Foramen Ovale and Atrial Septal Aneurysm.

The association between cryptogenic stroke (CS) and patent foramen ovale (PFO) with or without atrial septal aneurysm (ASA) has been a debate for decades in terms of pathophysiologic processes and clinical courses. This issue has become more interesting and complex, because of the concerns associating the CS with so-called normal variant pathologies of interatrial septum, namely ASA and PFO. While there is an anatomical pathology in the interatrial septum, namely PFO and ASA, the embolic source of stroke is not clearly defined. Moreover, in patients with PFO and CS, the risk of recurrent stroke has also been associated with other PFOunrelated factors, such as hyperlipidemia, body mass index, diabetes mellitus, and hypertension, leading to the difficulty in understanding the pathophysiologic mechanism of CS in patients with PFO and/or ASA. Theoretically, the embolic source of cryptogenic stroke in which PFO and/or ASA has been involved can be categorized into three different anatomical locations, namely PFO tissue and/or ASA tissue itself, right or left atrial chambers, and venous vascular territory distal to the right atrium, i.e., inferior vena cava and lower extremity venous system. However, the possible role of paroxysmal atrial fibrillation associated with PFO and/or ASA as a source of cryptogenic stroke has never been mentioned clearly in the literature. This review aims to explain the association of cryptogenic stroke with PFO and/or ASA in a comprehensive manner, including anatomical, clinical, and mechanistic aspects. The potential role of paroxysmal atrial fibrillation and its contribution to clinical course have been also discussed in a hypothetical manner to elucidate the pathophysiology of CS and support further treatment modalities.

Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke.

Altered left atrial metrics in patients with cryptogenic stroke: A systematic review and meta-analysis.

BACKGROUND: There is no defined cause for cryptogenic stroke/embolic stroke of undetermined source (CS-ESUS). As atrial fibrillation (AF) develops in a significant proportion of these patients, it has been suggested that left atrial (LA) myopathy may predispose to CS-ESUS. We investigated alterations in echocardiographic measures of LA size and function in patients with CS-ESUS. METHODS: A systematic literature review and meta-analysis was performed. PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS were searched for articles published between 1 January 1990 and 10 February 2023. All observational studies of adult CS-ESUS patients with LA volume or function measurements performed by transthoracic echocardiogram were included. Individual random effects meta-analyses were performed on LA measurements in the CS-ESUS patients using subgroup analysis of comparator groups. RESULTS: We included 29 articles with 3927 CS-ESUS patients. Analysis of weighted mean differences showed CS-ESUS patients had altered LA structure and function parameters, with a larger maximum indexed LA volume, reduced LA emptying fraction and/or LA reservoir strain, compared to healthy controls and noncardioembolic stroke patients. Conversely, CS-ESUS patients had a smaller left atrium with better function, compared to cardioembolic stroke patients and CS-ESUS patients who subsequently developed atrial fibrillation. CONCLUSIONS: LA volume and function are altered in CS-ESUS patients compared to healthy controls and other stroke aetiologies. An underlying atrial myopathy in a subset of CS-ESUS patients may be involved in both thrombogenesis and dysrhythmia (specifically AF). While LA functional assessment is not currently recommended following stroke, it may offer an opportunity for recurrent stroke risk stratification.