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Lacunar infarcts represent one of the most frequent subtypes of ischemic strokes and may represent the first recognizable manifestation of a progressive disease of the small perforating arteries, capillaries, and venules of the brain, defined as cerebral small vessel disease. The pathophysiological mechanisms leading to a perforating artery occlusion are multiple and still not completely defined, due to spatial resolution issues in neuroimaging, sparsity of pathological studies, and lack of valid experimental models. Recent advances in the endovascular treatment of large vessel occlusion may have diverted attention from the management of patients with small vessel occlusions, often excluded from clinical trials of acute therapy and secondary prevention. However, patients with a lacunar stroke benefit from early diagnosis, reperfusion therapy, and secondary prevention measures. In addition, there are new developments in the knowledge of this entity that suggest potential benefits of thrombolysis in an extended time window in selected patients, as well as novel therapeutic approaches targeting different pathophysiological mechanisms involved in small vessel disease. This review offers a comprehensive update in lacunar stroke pathophysiology and clinical perspective for managing lacunar strokes, in light of the latest insights from imaging and translational studies. [ABSTRACT FROM AUTHOR]

Introduction: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease (CSVD). We assessed whether the topography of RSSI was related to CSVD markers on magnetic resonance imaging (MRI).Material and Methods: We screened the local registries of two independent stroke centers in Catalonia and selected patients with a symptomatic RSSI on MRI performed during admission. RSSI location was classified into brainstem, supratentorial subcortical structures (SSS), and centrum semiovale (CSO) regions. Clinical variables, including vascular risk factors, were collected. Radiological markers of CSVD on MRI were evaluated individually and by means of the global CSVD burden score. The associations between each RSSI location and CSVD markers were studied in uni- and multivariate logistic regression analysis.Results: Among 475 patients with RSSI, 152 (32%) had an infarct in the brainstem, 227 (48%) in SSS, and 96 (20%) in CSO region. The median CSVD burden score was 2 (IQR, 1-3). After adjusting for confounding factors, a RSSI in CSO was associated with higher periventricular and deep white matter hyperintensity scores [OR 1.64 (95% CI, 1.16-2.33), and OR 1.44 (95% CI, 1.07-1.93), respectively]. Higher CSVD burden score was positively associated with CSO [OR 1.48 (95% CI, 1.22-1.81)] and inversely associated with SSS [0.85 (95% CI, 0.72-0.99)] location after adjusting for relevant confounders.Conclusions: CSO RSSI were related to a higher burden of CSVD, particularly to white matter hyperintensities, compared to other RSSI locations. The pathophysiological significance of such findings should be investigated in the future with advanced neuroimaging techniques. [ABSTRACT FROM AUTHOR]

Objectives: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease. Paramagnetic signals in perforating arteries supplying RSSI may be detected on T2*-relaxation derived sequences on MRI and is defined as susceptibility vessel sign (SVS). We aimed to study the prevalence of SVS in patients with RSSI, and explore whether its identification is related to cerebral small vessel disease markers.Materials and Methods: We selected patients with RSSI identified on MRI during admission from a single-center stroke registry. The main demographic and clinical features, including vascular risk factors, were collected. Radiological features of RSSI and cerebral small vessel disease [white matter hyperintensities in deep and periventricular regions, enlarged perivascular spaces, lacunae, microbleeds, and brain atrophy] were described using validated qualitative scores. The presence of SVS was assessed on T2*gradient-echo or other susceptibility-weighted imaging. We compared the clinical and radiological features of patients with or without SVS in uni- and multivariate models.Results: Out of 210 patients with an RSSI on an MRI, 35 (17%) showed SVS. The proportion of SVS+ patients was similar in different susceptibility imaging modalities (p=.64). Risk factor profiles and clinical course were similar in SVS+ and SVS- patients. SVS+ patients had a higher grade of deep white matter hyperintensities and brain atrophy, more lacunae (p=.001, p=.034, p=.022, respectively), and a similar degree of the rest of radiological variables, compared to SVS- patients. In the multivariate analysis, the grade of deep white matter hyperintensities was the only independent factor associated with SVS [OR 3.1 (95% CI, 1.5-6.4)].Conclusions: SVS in patients with RSSI is uncommon and related to a higher grade of deep white matter hyperintensities. Pathophysiological mechanisms underlying the deposition of hemosiderin in the path of occluded perforating arteries are uncertain and might include endothelial dysfunction or embolic mechanisms. [ABSTRACT FROM AUTHOR]

Hemichorea and other hyperkinetic movement disorders are a rare presentation of stroke, usually secondary to deep infarctions affecting the basal ganglia and the thalamus. Chorea can also result from lesions limited to the cortex, as shown in recent reports. Still, the pathophysiology of this form of cortical stroke-related chorea remains unknown. We report 4 cases of acute ischemic cortical strokes presenting as hemichorea, with the infarction being limited to the parietal and insular cortex in perfusion computed tomography scans and magnetic resonance imaging. These cases suggest potential dysfunction of pathways connecting these cortical regions with the basal ganglia. [ABSTRACT FROM AUTHOR]

The article discusses the experience of treating mechanical thrombectomy (MT) in infectious endocarditis (IE). It examines the complications in the use of revascularization and neurological recovery, main risk factors like central nervous system bleeding during revascularization and analyzing cases of endocarditis cohort.

In patients with infective endocarditis and neurological complications, the optimal timing for cardiac surgery is unclear due to the varied risk of clinical deterioration when early surgery is performed. The aim of this review is to summarize the best evidence on the optimal timing for cardiac surgery in the presence of each type of neurological complication. An English literature search was carried out from June 2018 through July 2022. The resulting selection, comprising observational studies, clinical trials, systematic reviews and society guidelines, was organized into four sections according to the four groups of neurological complications: ischemic, hemorrhagic, infectious, and asymptomatic complications. Cardiac surgery could be performed without delay in cases of ischemic vascular neurological complication (provided the absence of severe damage, which can be avoided with the performance of mechanical thrombectomy in cases of major stroke), as well as infectious or asymptomatic complications. In the presence of intracranial hemorrhage, a delay of four weeks is recommended for most cases, although recent studies have suggested that performing cardiac surgery within four weeks could be a suitable option for selected cases. The findings of this review are mostly in line with the recommendations of the current European and American infective endocarditis guidelines. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting. We obtained CD163+ cells from control rats and 16 h following transient middle cerebral artery occlusion, after verifying that infiltration of CD163+ peripheral myeloid cells is negligible at this acute time point. Transcriptome analysis of the sorted CD163+ cells identified ischemia-induced upregulation of the hypoxia inducible factor-1 pathway and induction of genes encoding for extracellular matrix components and leukocyte chemoattractants, amongst others. Using a cell depletion strategy, we found that CNS border-associated macrophages participate in granulocyte recruitment, promote the expression of vascular endothelial growth factor (VEGF), increase the permeability of pial and cortical blood vessels, and contribute to neurological dysfunction in the acute phase of ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and in some CD163+ perivascular macrophages in the brain tissue of ischemic stroke patients deceased one day after stroke onset. These findings show ischemia-induced reprogramming of the gene expression profile of CD163+ macrophages that has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and promotes neurological impairment in the acute phase of stroke. [ABSTRACT FROM AUTHOR]

Vascular endothelial function is challenged during cerebral ischemia and reperfusion. The endothelial responses are involved in inflammatory leukocyte attraction, adhesion and infiltration, blood–brain barrier leakage, and angiogenesis. This study investigated gene expression changes in brain endothelial cells after acute ischemic stroke using transcriptomics and translatomics. We isolated brain endothelial mRNA by: (i) translating ribosome affinity purification, enabling immunoprecipitation of brain endothelial ribosome-attached mRNA for translatome sequencing and (ii) isolating CD31+ endothelial cells by fluorescence-activating cell sorting for classical transcriptomic analysis. Both techniques revealed similar pathways regulated by ischemia but they showed specific differences in some transcripts derived from non-endothelial cells. We defined a gene set characterizing the endothelial response to acute stroke (24h) by selecting the differentially expressed genes common to both techniques, thus corresponding with the translatome and minimizing non-endothelial mRNA contamination. Enriched pathways were related to inflammation and immunoregulation, angiogenesis, extracellular matrix, oxidative stress, and lipid trafficking and storage. We validated, by flow cytometry and immunofluorescence, the protein expression of several genes encoding cell surface proteins. The inflammatory response was associated with the endothelial upregulation of genes related to lipid storage functions and we identified lipid droplet biogenesis in the endothelial cells after ischemia. The study reports a robust translatomic signature of brain endothelial cells after acute stroke and identifies enrichment in novel pathways involved in membrane signaling and lipid storage. Altogether these results highlight the endothelial contribution to the inflammatory response, and identify novel molecules that could be targets to improve vascular function after ischemic stroke. [ABSTRACT FROM AUTHOR]

Treatments for acute ischaemic stroke continue to evolve after the superior value of endovascular thrombectomy was confirmed over systemic thrombolysis. Unfortunately, numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischaemic stroke, making the search for new treatments imperative. Increased awareness of the relevance of rigorous preclinical testing, and appropriate selection of study participants, might overcome the barriers to progress in stroke research. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials. Randomised controlled trials of combination treatments completed within the past 5 years have included growth factors, hypothermia, minocycline, natalizumab, fingolimod, and uric acid; the latter two drugs with alteplase produced encouraging results. Blocking of excitotoxicity is also being reassessed in clinical trials with new approaches, such as the postsynaptic density-95 inhibitor NA-1, or peritoneal dialysis to remove excess glutamate. The findings of these randomised trials are anticipated to improve treatment options and clinical outcomes in of patients with acute stroke. [ABSTRACT FROM AUTHOR]

Purpose: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion.Methods: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion.Results: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion.Conclusions: Fluid exchanges between perivascular spaces (PVS) and interstitium may contribute to the pathophysiology of small vessel disease (SVD). We aimed to analyze water diffusivity measures and their relationship with PVS and other SVD imaging markers.We enrolled 50 consecutive patients with a recent small subcortical infarct. We collected clinical variables, including vascular risk factors and sleep quality scales. All patients underwent a 3-Tesla MRI with standard structural sequences and multishell-diffusion images to obtain extracellular free water content (FW) and water diffusivity along the perivascular space (ALPS) index. We obtained volumetric measurements of white matter hyperintensities (WMH) and PVS, and the number of lacunes and microbleeds. To analyze the association between PVS, ALPS index, FW, and SVD imaging features, we utilized linear regression models including age, sex, history of hypertension and diabetes, Pittsburgh Sleep Quality Index, WMH, and brain volume.All patients (mean age 70 years, 36% women) had usable data. FW and PVS were strongly associated in all models (0.008 < Beta < 0.054; P < 0.045). Higher FW was related to the other SVD features in univariable models and remained significant for WMH (1.175 < Beta < 1.262; P < 0.001) and brain volume (Beta < 0.0001; P < 0.002) in multivariable models. ALPS index was not associated with FW, PVS, or any other SVD markers.The increased extracellular water in SVD suggests that impaired brain fluid exchanges, PVS dilation, and other SVD features are linked. Further investigation is needed to determine the specificity of the ALPS index to PVS diffusion. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are professional antigen presenting cells that constantly survey the environment acting as sentinels of the immune system, including in the CNS. DCs are strategically located near the cerebrospinal fluid, but they can potentially migrate to draining cervical lymph nodes either triggering immunogenic T cell responses or displaying tolerogenic functions. Under physiological conditions, the presence of DCs in the brain parenchyma is minimal but their numbers increase in neuroinflammation. Although DCs belong to a distinct immune cell lineage, they show various phenotypes and share certain common markers with monocytes, macrophages, and microglia. All these cells can express major histocompatibility complex class II, and acquire similar morphologies hampering their precise identification. Neuroinflammation is increasingly recognized in many brain disorders; here we review the literature reporting DCs in the inflamed brain in disease conditions and corresponding animal models of multiple sclerosis, stroke, brain tumors, Alzheimer's disease, Parkinson's disease, and epilepsy. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy. Methods: This single‐center, randomized, double‐blind, placebo‐controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near‐normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra‐arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion‐weighted magnetic resonance imaging (MRI) and MRI‐spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N‐acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity. Results: The prevalence of hypoperfusion was 24% with intra‐arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04–0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5–1.2] vs 3.2 [1.8–5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91–1.36] vs 1.00 [0.74–1.22], p < 0.0001). Interpretation: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022;92:860–870 [ABSTRACT FROM AUTHOR]

Abstract: Heat shock protein 70 (Hsp-70) can act as a danger signal and activate immune responses. We studied the presence of Hsp-70 in lymphoid tissue and plasma of acute stroke patients and asymptomatic controls free of neurological disease. Immunofluorescence, Western blotting, qRT-PCR and flow cytometry studies were performed. Plasma Hsp-70 concentration at day 7 was similar in patients and controls, whereas patients disclosed stronger immunoreactivity to Hsp-70 in lymphoid tissue than controls. Most Hsp-70+ cells were antigen presenting cells located in T cell zones. Stronger immunoreactivity to Hsp-70 was associated with smaller infarctions and better functional outcome. [Copyright &y& Elsevier]

Objectives: After an acute ischemic stroke, patients with a large CT perfusion (CTP) predicted infarct core (pIC) have poor clinical outcome. However, previous research suggests that this relationship may be relevant for subgroups of patients determined by pretreatment and treatment-related variables while negligible for others. We aimed to identify these variables. Methods: We included a cohort of 828 patients with acute proximal carotid arterial occlusions imaged with a whole-brain CTP within 8 h from stroke onset. pIC was computed on CTP Maps (cerebral blood flow < 30%), and poor clinical outcome was defined as a 90-day modified Rankin Scale score > 2. Potential mediators of the association between pIC and clinical outcome were evaluated through first-order and advanced interaction analyses in the derivation cohort (n = 654) for obtaining a prediction model. The derived model was further validated in an independent cohort (n = 174). Results: The volume of pIC was significantly associated with poor clinical outcome (OR = 2.19, 95% CI = 1.73 – 2.78, p < 0.001). The strength of this association depended on baseline National Institute of Health Stroke Scale, glucose levels, the use of thrombectomy, and the interaction of age with thrombectomy. The model combining these variables showed good discrimination for predicting clinical outcome in both the derivation cohort and validation cohorts (area under the receiver operating characteristic curve 0.780 (95% CI = 0.746–0.815) and 0.782 (95% CI = 0.715–0.850), respectively). Conclusions: In patients imaged within 8 h from stroke onset, the association between pIC and clinical outcome is significantly modified by baseline and therapeutic variables. These variables deserve consideration when evaluating the prognostic relevance of pIC. Key Points: •The volume of CT perfusion (CTP) predicted infarct core (pIC) is associated with poor clinical outcome in acute ischemic stroke imaged within 8 h of onset. •The relationship between pIC and clinical outcome may be modified by baseline clinical severity, glucose levels, thrombectomy use, and the interaction of age with thrombectomy. •CTP pIC should be evaluated in an individual basis for predicting clinical outcome in patients imaged within 8 h from stroke onset. [ABSTRACT FROM AUTHOR]

Background: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.Methods: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.Findings: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087).Interpretation: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window.Funding: Stryker Neurovascular. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. Aim: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. Methods: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). Results: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. Conclusions: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes. [ABSTRACT FROM AUTHOR]

Emergent stent placement may be required during neurothrombectomy. Our aim was to investigate the incidence, predictors and clinical relevance of early extracranial carotid stent occlusion following neurothrombectomy. We retrospectively analyzed a cohort of 761 consecutive neurothrombectomies performed at our center between May 2010 and August 2018, from whom a total of 106 patients had acute internal carotid artery occlusions. Early stent occlusion was defined as complete vessel occlusion within 24 h of neurothrombectomy. Clinical outcome was evaluated at day 90 with the modified Rankin Score scale (mRS). Pretreatment, procedural and outcome variables were recorded and analyzed using logistic regression. Carotid stenting was performed in 99 (13%) patients. Of those, 22 (22%) had early stent occlusion at follow-up. Stent occlusion was associated with a lower use of post-stenting angioplasty [adjusted OR (aOR) = 11.2, 95%CI = 2.49–50.78, p = 0.002)], increased residual intrastent stenosis (aOR = 2.1, 95%CI = 1.38–3.06, p < 0.001) and unsuccesful intracranial recanalization (modified TICI score 0-2a) (aOR = 13.5, 95%CI = 1.97–92.24, p = 0.008). Stent occlusion was associated with poor clinical outcome at day 90 (poorer mRS shift, aOR = 3.9, 95%CI = 1.3–11.3, p = 0.014; mRS>2, aOR = 6.3, 95%CI = 1.8–22.7, p = 0.005), and with an increased rate of symptomatic intracranial hemorrhage at 24 h (14% versus 1%, p = 0.033). Early carotid stent occlusion occurred in one out of five neurothrombectomies and was associated with periprocedural factors that included increased residual intrastent stenosis, a lower use of post-stenting angioplasty and unsuccessful intracranial recanalization. Further investigation is warranted for the evaluation of strategies aimed to prevent carotid stent occlusion. Image 1 • Stent thrombosis occurs in one fifth of the patients treated with acute stenting. • Stent thrombosis is associated with specific procedural variables. • Stent thrombosis is associated with poor clinical outcome. • Further investigation of strategies aimed to prevent stent occlusion is needed. [ABSTRACT FROM AUTHOR]

Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as regions with cerebral blood volume (CBV) values < 2.5% of normal brain [very-low CBV (VLCBV)-regions]. Median baseline glucose levels were 119 (IQR = 105–141) mg/dL. Thirty-nine (15%) patients had pretreatment VLCBV-regions, and 42 (16%) developed a PH after MT. In adjusted models, pretreatment glucose levels interacted significantly with VLCBV on the prediction of PH (p-interaction = 0.011). In patients with VLCBV-regions, higher glucose was significantly associated with PH (adjusted-OR = 3.15; 95% CI = 1.08–9.19, p = 0.036), whereas this association was not significant in patients without VLCBV-regions. CBV values measured at pretreatment CTP in coregistered regions that developed PH or infarct at follow-up were not correlated with pretreatment glucose levels, thus suggesting the existence of alternative deleterious mechanisms other than direct glucose-driven hemodynamic impairments. Overall, these results suggest that both severe hypoperfusion and glucose levels should be considered in the evaluation of adjunctive neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Computed tomography perfusion (CTP) allows the estimation of pretreatment ischemic core after acute ischemic stroke. However, CTP-derived ischemic core may overestimate final infarct volume. We aimed to evaluate the accuracy of CTP-derived ischemic core for the prediction of final infarct volume according to time from stroke onset to recanalization in 104 patients achieving complete recanalization after mechanical thrombectomy who had a pretreatment CTP and a 24-h follow-up MRI-DWI. A range of CTP thresholds was explored in perfusion maps at constant increments for ischemic core calculation. Time to recanalization modified significantly the association between ischemic core and DWI lesion in a non-linear fashion (p -interaction = 0.018). Patients with recanalization before 4.5 h had significantly lower intraclass correlation coefficient (ICC) values between CTP-predicted ischemic core and DWI lesion (n = 54; best threshold relative cerebral blood flow (rCBF) < 25%, ICC = 0.673, 95% CI = 0.495–0.797) than those with later recanalization (n = 50; best threshold rCBF < 30%, ICC = 0.887, 95% CI = 0.811–0.935, p = 0.013), as well as poorer spatial lesion agreement. The significance of the associations between CTP-derived ischemic core and clinical outcome at 90 days was lost in patients recanalized before 4.5 h. CTP-derived ischemic core must be interpreted with caution given its dependency on time to recanalization, primarily in patients with higher chances of early recanalization. [ABSTRACT FROM AUTHOR]

Background and purpose: Ischemic stroke (IS) and hemorrhagic stroke (HemS) typically lead to a breakdown of the blood–brain barrier with neural antigen presentation. This presentation could potentially generate destructive auto-immune responses. Pre-existing antineuronal and antiglial antibodies (AA), predominantly NMDA receptor antibodies, have been reported in patients with stroke. This article summarizes three independent prospective studies, the Lübeck cohort (LC), Barcelona cohort (BC), and Heidelberg cohort (HC), exploring the frequency and clinical relevance of AA in patients with acute stroke (AS). Methods: In all cohorts together, 344 consecutive patients admitted with AS (322 × IS, 22 × HemS) were screened for AA in serum at admission. Clinical outcome parameters as well as a second AA screening were available at 30 days in the LC or at 90 days in the BC. A control group was included in the BC (20 subjects free from neurological disease) and the HC (78 neurological and ophthalmological patients without evidence for stroke). Results: The rate of positivity for AA was similar in control subjects and AS patients (13%, 95% CI [7%, 22%] vs. 13%, 95% CI [10%, 17%]; p = 0.46) with no significant difference between cohorts (LC 25/171, BC 12/75, HC 9/98). No patient had developed new AA after 30 days, whereas 2 out of 60 patients had developed new AA after 90 days. AA positive patients did not exhibit significant differences to AA negative patients in stroke subtype (LC, BC), initial stroke severity (BC, LC, HC), infarct volume (BC), and functional status at admission (BC, LC, HC) and follow-up (BC, LC). Conclusions: AS does not induce AA to a relevant degree. Pre-existing AA can be found in the serum of stroke patients, but they do not have a significant association with clinical features and outcomes. [ABSTRACT FROM AUTHOR]

Hypoperfusion is the typical perfusion pattern associated with recent small subcortical infarcts of the brain, but other perfusion patterns may be present in patients with these infarcts. Using CT perfusion, we studied 67 consecutive patients who had a small subcortical infarct at a follow-up MRI study to investigate the correlation between the perfusion pattern and the clinical and radiological course. On CT perfusion map analysis, 51 patients (76%) had focal hypoperfusion, 4 patients (6%) had hyperperfusion and the remaining 12 patients (18%) showed no abnormalities. On dynamic sequential imaging analysis obtained from the source perfusion images, 32 patients (48%) had a sustained hypoperfusion pattern, 11 patients (16%) had a reperfusion pattern, and 18 patients (27%) had a delayed compensation pattern. Systolic blood pressure was higher in patients with sustained hypoperfusion although the perfusion pattern was independent of the final volume of infarction. These results reinforce the notion that mechanisms other than hypoperfusion are at play in patients with small subcortical infarcts including the intervention of compensatory sources of blood flow. The ultimate clinical significance of these perfusion patterns remains to be determined in larger series of patients assessed longitudinally. [ABSTRACT FROM AUTHOR]

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30–21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose To assess the reliability of the Fazekas score on brain CT in acute stroke patients. Methods Two raters evaluated the Fazekas score in 157 CT scans from consecutive patients with acute stroke. Results The Fazekas scores on brain CT scans showed consistent (weighted κ, 0.73) and moderate (weighted κ, 0.56) interobserver agreement for periventricular and deep white matter areas, respectively. Intraobserver reliability was substantial for both areas (weighted κ, 0.85 and 0.8). Conclusion The Fazekas score on CT can be used to reliably grade white matter changes, and can be a useful tool when MRI is not available. [ABSTRACT FROM AUTHOR]

Endovascular reperfusion therapy is increasingly used for acute ischemic stroke treatment. The occurrence of parenchymal hemorrhage is clinically relevant and increases with reperfusion therapies. Herein we aimed to examine the optimal perfusion CT-derived parameters and the impact of the duration of brain ischemia for the prediction of parenchymal hemorrhage after endovascular therapy. A cohort of 146 consecutive patients with anterior circulation occlusions and treated with endovascular reperfusion therapy was analyzed. Recanalization was assessed at the end of reperfusion treatment, and the rate of parenchymal hemorrhage at follow-up neuroimaging. In regression analyses, cerebral blood volume and cerebral blood flow performed better than Delay Time maps for the prediction of parenchymal hemorrhage. The most informative thresholds (receiver operating curves) for relative cerebral blood volume and relative cerebral blood flow were values lower than 2.5% of normal brain. In binary regression analyses, the volume of regions with reduced relative cerebral blood volume and/or relative cerebral blood flow was significantly associated with an increased risk of parenchymal hemorrhage, as well as delayed vessel recanalization. These results highlight the relevance of the severity and duration of ischemia as drivers of blood-brain barrier disruption in acute ischemic stroke and support the role of perfusion CT for the prediction of parenchymal hemorrhage. [ABSTRACT FROM AUTHOR]

Acute stroke induces a local inflammatory reaction causing leukocyte infiltration. Circulating monocytes are recruited to the ischemic brain and become tissue macrophages morphologically indistinguishable from reactive microglia. However, monocytes are a heterogeneous population of cells with different functions. Herein, we investigated the infiltration and fate of the monocyte subsets in a mouse model of focal brain ischemia by permanent occlusion of the distal portion of the middle cerebral artery. We separated two main subtypes of CD11b hi monocytes according to their expression of the surface markers Ly6C and CD43. Using adoptive transfer of reporter monocytes and monocyte depletion, we identified the pro-inflammatory Ly6C hi CD43 lo CCR2 + subset as the predominant monocytes recruited to the ischemic tissue. Monocytes were seen in the leptomeninges from where they entered the cortex along the penetrating arterioles. Four days post-ischemia, they had invaded the infarcted core, where they were often located adjacent to blood vessels. At this time, Iba-1 − and Iba-1 + cells in the ischemic tissue incorporated BrdU, but BrdU incorporation was rare in the reporter monocytes. The monocyte phenotype progressively changed by down-regulating Ly6C, up-regulating F4/80, expressing low or intermediate levels of Iba-1, and developing macrophage morphology. Moreover, monocytes progressively acquired the expression of typical markers of alternatively activated macrophages, like arginase-1 and YM-1. Collectively, the results show that stroke mobilized immature pro-inflammatory Ly6C hi CD43 lo monocytes that acutely infiltrated the ischemic tissue reaching the core of the lesion. Monocytes differentiated to macrophages with features of alternative activation suggesting possible roles in tissue repair during the sub-acute phase of stroke. [ABSTRACT FROM AUTHOR]

Objective Acquired anomalies of the dural venous sinuses (DVS) have been correlated extensively with the development of dural arteriovenous fistulas (DAVFs). Despite the known similarities of DAVFs' pathogenesis with that of arteriovenous malformations (AVMs), the relationship of venous sinuses anomalies with AVMs scarcely has been studied. We aimed to investigate whether patients with AVM show a greater prevalence of congenital DVS anomalies. We hypothesized that these congenital anomalies trigger AVM development during early childhood just as acquired DVS anomalies trigger DAVFs formation during adulthood. Methods Angiographic anomalies of the brain venous sinuses were studied in a cohort of 45 consecutive patients with AVM and compared with the angiographic; venous sinus anomalies of a control group formed by a second consecutive; series of 45 patients with subarachnoid hemorrhage. Results Congenital anomalies of any DVS were more frequent in patients with AVM than in the control group (49.8% vs. 22.2%; P = 0.015). Congenital abnormalities of the superior sagittal sinus not only were more frequent in patients with AVM (27% vs. 6.7%; P = 0.021) but seemed also related to the AVM location: in 5 of the 6 AVM cases with unilateral superior sagittal sinus aplasia, the AVM was ipsilateral to the venous anomaly. Conclusions Patients with AVM have a greater likelihood of congenital anomalies of any DVS. These anomalies seem to be related also to the AVM location. These findings suggest that congenital anomalies of DVS may be related to the development of AVMs. [ABSTRACT FROM AUTHOR]

Objectives: Acute ischemic strokes (stroke) are frequent and severe extracardiac complications in infective endocarditis (IE). Since intravenous thrombolysis (IV-thrombolysis) is contraindicated, mechanical thrombectomy (thrombectomy) offers potential benefit. We aimed to compare thrombectomy efficacy and safety between IE-related and general stroke cases., Methods: Multicenter study of consecutive IE cases treated with thrombectomy at nine stroke centers in Spain from 2011 to 2022. Using propensity score matching, 50 IE cases were 1:4 matched with non-IE stroke patients (n=200). Efficacy was defined by successful recanalization rates [modified treatment in cerebral ischemia scale (mTICI) ≥2b], neurological improvement at 24 hours [decrease of National Institutes of Health Stroke Scale (NIHSS) compared to baseline], and good neurological outcome rates at 3 months [modified Rankin scale (mRS) ≤ 2]. Safety was assessed by intracranial hemorrhage (IC-hemorrhage), symptomatic IC-hemorrhage, crude mortality, and stroke-related mortality., Results: Among 54 IE cases, 50 were matched with 200 controls. Successful recanalization was similarly achieved in both groups (76% vs 83%). Median NIHSS at 24h was comparable, with analogous rates of neurological improvement (78% vs 78%), and early dramatic response (48% vs 46.5%). No differences were seen regarding IC-hemorrhage rates, except for when prior IV-thrombolysis was given. Although crude mortality was higher in the IE cohort, no differences were seen in stroke-related mortality (12% vs 15%). At three months, mRS scores of the two groups were superimposable., Conclusions: Thrombectomy in IE is as effective and safe as in non-IE patients, and prior IV-thrombolysis could decrease the procedural safety. Clinical practice guidelines may consider including the recommendation to perform thrombectomy alone in IE-related stroke., (Copyright © 2025 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary veins integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct., Materials and Methods: We gathered demographic, clinical, and 3 Tesla-MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluate the venular integrity using two visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary-small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score., Results: In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter and DTI-along the perivascular spaces, were associated with one or both venular scores. In multivariate analysis (OR, 95% CI), free water (1.33, 1.03-1.73), mean diffusivity (4.56, 1.32-15.81), fractional anisotropy (0.77, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (2.39, 1.06-5.39;0.78, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (0.48, 0.25-0.94), fractional anisotropy with and without free water correction (0.82,0.86-0.99; 0.83, 0.7-0.99, respectively) remained significant for vein count., Conclusions: In patients with a recent small subcortical infarct, disruption of the deep medullary veins, increased extracellular water, and white matter injury appear to be associated., Abbreviations: SVD=small vessel disease; DMV=deep medullary veins; WMH=white matter hyperintensities; PVS=perivascular spaces; DTI-ALPS=diffusion tensor image analysis along the perivascular spaces; FW=free water; MD=mean diffusivity; FA= fractional anisotropy; BG=basal ganglia., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Importance: Prehospital transfer protocols are based on rapid access to reperfusion therapies for patients with ischemic stroke. The effect of different protocols among patients receiving a final diagnosis of intracerebral hemorrhage (ICH) is unknown., Objective: To determine the effect of direct transport to an endovascular treatment (EVT)-capable stroke center vs transport to the nearest local stroke center., Design, Setting, and Participants: This was a prespecified secondary analysis of RACECAT, a multicenter, population-based, cluster-randomized clinical trial conducted from March 2017 to June 2020 in Catalonia, Spain. Patients were evaluated by a blinded end point assessment. All consecutive patients suspected of experiencing a large vessel occlusion stroke (Rapid Arterial Occlusion Evaluation Scale [RACE] score in the field >4 on a scale of 0 to 9, with lower to higher stroke severity) with final diagnosis of ICH were included. A total of 1401 patients were enrolled in RACECAT with suspicion of large vessel occlusion stroke. The current analysis was conducted in October 2022., Intervention: Direct transport to an EVT-capable stroke center (n = 137) or to the closest local stroke center (n = 165)., Main Outcomes and Measures: The primary outcome was tested using cumulative ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI of the shift analysis of disability at 90 days as assessed by the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) in the intention-to-treat population. Secondary outcomes, included 90-day mortality, death or severe functional dependency, early neurological deterioration, early mortality, ICH volume and enlargement, rate of neurosurgical treatment, rate of clinical complications during initial transport, and rate of adverse events until day 5., Results: Of 1401 patients enrolled, 1099 were excluded from this analysis (32 rejected informed consent, 920 had ischemic stroke, 29 had transient ischemic attack, 12 had subarachnoid hemorrhage, and 106 had stroke mimic). Thus, 302 patients were included (204 [67.5%] men; mean [SD] age 71.7 [12.8] years; and median [IQR] RACE score, 7 [6-8]). For the primary outcome, direct transfer to an EVT-capable stroke center (mean [SD] mRS score, 4.93 [1.38]) resulted in worse functional outcome at 90 days compared with transfer to the nearest local stroke center (mean [SD] mRS score, 4.66 [1.39]; adjusted common OR, 0.63; 95% CI, 0.41-0.96). Direct transfer to an EVT-capable stroke center also suggested potentially higher 90-day mortality compared with transfer to the nearest local stroke center (67 of 137 [48.9%] vs 62 of 165 [37.6%]; adjusted hazard ratio, 1.40; 95% CI, 0.99-1.99). The rates of medical complications during the initial transfer (30 of 137 [22.6%] vs 9 of 165 patients [5.6%]; adjusted OR, 5.29; 95% CI, 2.38-11.73) and in-hospital pneumonia (49 of 137 patients [35.8%] vs 29 of 165 patients [17.6%]; OR, 2.61; 95% CI, 1.53-4.44) were higher in the EVT-capable stroke center group., Conclusions and Relevance: In this secondary analysis of the RACECAT randomized clinical trial, bypassing the closest stroke center resulted in reduced chances of functional independence at 90 days for patients who received a final diagnosis of ICH., Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

Background: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection., Methods: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments., Results: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae., Conclusions: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection., Competing Interests: Disclosures None.

Objectives: To study prehospital care process in relation to hospital outcomes in stroke-code cases first attended by 2 different levels of ambulance. To analyze factors associated with a satisfactory functional outcome at 3 months., Material and Methods: Prospective multicenter observational cohort study. All stroke-code cases attended by prehospital emergency services from January 2016 to April 2022 were included. Prehospital and hospital variables were collected. The classificatory variable was type of ambulance attending (basic vs advanced life support). The main outcome variables were mortality and functional status after ischemic strokes in patients who underwent reperfusion treatment 90 days after the ischemic episode., Results: Out of 22 968 stroke-code activations, ischemic stroke was diagnosed in 12 467 patients (54.3%) whose functional status was good before the episode. Basic ambulances attended 93.1%; an advanced ambulance was ordered in 1.6% of the patients. Even though there were differences in patient and clinical characteristics recorded during the prehospital process, type of ambulance was not independently associated with mortality (adjusted odds ratio [aOR], 1.1; 95% CI, 0.77-1.59) or functional status at 3 months (aOR, 1.05; 95% CI, 0,72-1,47)., Conclusion: The percentage of patient complications in stroke-code cases attended by basic ambulance teams is low. Type of ambulance responding was not associated with either mortality or functional outcome at 3 months in this study.

Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion)., Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics., Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2-5] versus 3 [1-5], common odds ratio, 1.25 [95% CI, 1.06-1.48]); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08-1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81-1.28]). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16-1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51-0.75]), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25-52]) and thrombectomy(mean difference 66 minutes [95% CI, 37-95])., Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02795962.

Background and Purpose: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors., Methods: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted., Results: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p &lt; 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p &lt; 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p &lt; 0.001)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates., (© 2022 European Academy of Neurology.)

Background: The mechanisms and outcomes in coronavirus disease (COVID-19)-associated stroke are unique from those of non-COVID-19 stroke., Objective: To describe the efficacy and outcomes of acute revascularization of large vessel occlusion (LVO) in the setting of COVID-19 in an international cohort., Methods: We conducted an international multicenter retrospective study of consecutively admitted patients with COVID-19 with concomitant acute LVO across 50 comprehensive stroke centers. Our control group constituted historical controls of patients presenting with LVO and receiving a mechanical thrombectomy between January 2018 and December 2020., Results: The total cohort was 575 patients with acute LVO; 194 patients had COVID-19 while 381 patients did not. Patients in the COVID-19 group were younger (62.5 vs 71.2; P < .001) and lacked vascular risk factors (49, 25.3% vs 54, 14.2%; P = .001). Modified thrombolysis in cerebral infarction 3 revascularization was less common in the COVID-19 group (74, 39.2% vs 252, 67.2%; P < .001). Poor functional outcome at discharge (defined as modified Ranklin Scale 3-6) was more common in the COVID-19 group (150, 79.8% vs 132, 66.7%; P = .004). COVID-19 was independently associated with a lower likelihood of achieving modified thrombolysis in cerebral infarction 3 (odds ratio [OR]: 0.4, 95% CI: 0.2-0.7; P < .001) and unfavorable outcomes (OR: 2.5, 95% CI: 1.4-4.5; P = .002)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor outcomes in patients with stroke due to LVO. Patients with COVID-19 with LVO were younger, had fewer cerebrovascular risk factors, and suffered from higher morbidity/mortality rates., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces ( n = 52) during the first wave of the pandemic (weeks 10-16 of 2020)., Methods: We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces., Results: We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03% in < 50-year-old, 0.22% in 50-59-year-old, 0.9% in 60-69-year-old, 3.3% in 70-79-year-old, 12.6% in 80-89-year-old, and 26.5% in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population., Conclusion: The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background and Purpose:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors., Methods:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria)., Results:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3)., Conclusions:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Objective: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI., Methods: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery -Timepoint 1- (Tp1) and at the 6-to-12-month follow-up -Timepoint2- (Tp2)., Results: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate post-surgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005)., Conclusions: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs., Competing Interests: Declaration of Competing Interest All the authors listed in the manuscript certify that, to the best of their knowledge, no aspect of their personal or professional circumstances currently, or in the past 12 months, places any of them in the position of having a conflict of interest with any entity that may potentially benefit from, or be harmed by, the publication of the results of this study., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view., Methods: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days., Results: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period., Conclusion: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately., (© 2021 S. Karger AG, Basel.)

Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19., Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality., Secondary Outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage., Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH)., Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.

Rationale: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials., Aim: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy., Sample Size Estimates: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up)., Methods and Design: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg)., Study Outcome(s): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed., Discussion: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

About half of acute stroke patients treated with mechanical thrombectomy (MT) do not show clinical improvement despite successful recanalization. Early arterial reocclusion (EAR) may be one of the causes that explain this phenomenon. We aimed to analyze the incidence and clinico-radiological correlations of EAR after successful MT. A consecutive series of patients treated with MT between 2010 and 2018 at a single-center included in a prospective registry was retrospectively reviewed. Specific inclusion criteria for the analysis were (1) successful recanalization after MT and (2) availability of pretreatment CT perfusion and follow-up MRI. EAR was evaluated in the follow-up MR angiography. Adjusted regression models were used to analyze the association of EAR with pretreatment variables, infarct growth, final infarct volume, and clinical outcome at 90 days (ordinal distribution of the modified Rankin Scale scores). Out of 831 MT performed, 218 (26%) patients fulfilled inclusion criteria, from whom 13 (6%) suffered EAR. In multivariate analysis controlled by confounders, EAR was independently associated with poor clinical outcome (aOR = 3.2, 95%CI = 1.16-9.72, p = 0.039), greater final infarct volume (aOR = 3.8, 95%CI = 1.93-7.49, p < 0.001), and increased infarct growth (aOR = 8.5, CI95% = 2.04-34.70, p = 0.003). According to mediation analyses, the association between EAR and poor clinical outcome was mainly explained through its effects on final infarct volume and infarct growth. Additionally, EAR was associated with non-cardioembolic etiology (adjusted Odds Ratio (aOR) = 10.1, 95%CI = 1.25-81.35, p = 0.030) and longer procedural time (aOR = 2.6, 95%CI = 1.31-5.40, p = 0.007). Although uncommon, EAR hampers the benefits of successful recanalization after MT resulting in increased infarct growth and larger final lesions.

Background and Purpose: Reliable recognition of large vessel occlusion (LVO) on noncontrast computed tomography (NCCT) may accelerate identification of endovascular treatment candidates. We aim to validate a machine learning algorithm (MethinksLVO) to identify LVO on NCCT., Methods: Patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. Software detection of LVO (MethinksLVO) on NCCT was tested against the CTA readings of 2 experienced radiologists (NR-CTA). We used a deep learning algorithm to identify clot signs on NCCT. The software image output trained a binary classifier to determine LVO on NCCT. We studied software accuracy when adding National Institutes of Health Stroke Scale and time from onset to the model (MethinksLVO+)., Results: From 1453 patients, 823 (57%) had LVO by NR-CTA. The area under the curve for the identification of LVO with MethinksLVO was 0.87 (sensitivity: 83%, specificity: 71%, positive predictive value: 79%, negative predictive value: 76%) and improved to 0.91 with MethinksLVO+ (sensitivity: 83%, specificity: 85%, positive predictive value: 88%, negative predictive value: 79%)., Conclusions: In patients with suspected acute stroke, MethinksLVO software can rapidly and reliably predict LVO. MethinksLVO could reduce the need to perform CTA, generate alarms, and increase the efficiency of patient transfers in stroke networks.