Hypoperfusion index ratio and pretreatment with intravenous thrombolysis are independent predictors of good functional outcome in acute ischemic stroke patients with large vessel occlusion treated with acute reperfusion therapies.

INTRODUCTION: We aimed to investigate the performance of several neuroimaging markers provided by perfusion imaging of Acute Ischemic Stroke (AIS) patients with large vessel occlusion (LVO) in order to predict clinical outcomes following reperfusion treatments. METHODS: We prospectively evaluated consecutive AIS patients with LVO who were treated with reperfusion therapies, during a six-year period. In order to compare patients with good (mRS scores 0-2) and poor (mRS scores 3-6) functional outcomes, data regarding clinical characteristics, the Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), CT angiography collateral status and perfusion parameters including ischemic core, hypoperfusion volume, mismatch volume between core and penumbra, Tmax > 10 s volume, CBV index and the Hypoperfusion Index Ratio (HIR) were assessed. RESULTS: A total of 84 acute stroke patients with LVO who met all the inclusion criteria were enrolled. In multivariable logistic regression models increasing age (odds ratio [OR]: 0.93; 95%CI: 0.88-0.96, p = 0.001), lower admission National Institute of Health Stroke Scale (NIHSS)-score (OR: 0.88; 95%CI: 0.80-0.95, p = 0.004), pretreatment with intravenous thrombolysis (OR: 3.83; 95%CI: 1.29-12.49, p = 0.019) and HIR (OR:0.36; 95%CI: 0.10-0.95, p = 0.042) were independent predictors of good functional outcome at 3 months. The initial univariable associations between HIR and higher likelihood for symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2) were attenuated in multivariable analyses failing to reach statistical significance. DISCUSSION: Our pilot observational study of unselected AIS patients with LVO treated with reperfusion therapies demonstrated that pre-treatment low HIR in perfusion imaging and IVT were associated with better functional outcomes.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

Medical Management Versus Endovascular Treatment for Large-Vessel Occlusion Anterior Circulation Stroke With Low NIHSS.

BACKGROUND: Endovascular treatment (EVT) for acute ischemic stroke (AIS) patients presenting with National Institutes of Health Stroke Scale score of 0 to 5 is common in clinical practice but has not yet been proven safe and effective. Our objective is to assess whether EVT on top of best medical treatment (BMT) in AIS patients with large-vessel occlusion of the anterior circulation presenting with mild symptoms is beneficial compared with BMT. METHODS: We searched MEDLINE, SCOPUS, and reference lists of retrieved articles published until December 28, 2022. A systematic literature search was conducted to identify clinical trials or observational cohort studies evaluating patients with AIS due to anterior circulation large-vessel occlusion and admission National Institutes of Health Stroke Scale score ≤5 treated with EVT versus BMT alone. The primary outcome was excellent functional outcome (modified Rankin Scale score 0-1) at 3 months. The protocol had been registered before data collection (PROSPERO). RESULTS: Eleven observational eligible studies were included in the meta-analysis, comprising a total of 2019 AIS patients with National Institutes of Health Stroke Scale score ≤5 treated with EVT versus 3171 patients treated with BMT. EVT was not associated with excellent functional outcome (risk ratio, 1.10 [95% CI, 0.93-1.31]). When stratified for different study design (per-protocol versus intention-to-treat), there were no significant subgroup differences. EVT was not associated with good functional outcome (modified Rankin Scale score 0-2; risk ratio, 1.01 [95% CI, 0.89-1.16]) or reduced disability at 3 months (common odds ratio, 0.92 [95% CI, 0.60-1.41]). Symptomatic intracranial hemorrhage was more common in the patients receiving EVT (risk ratio, 3.53 [95% CI, 2.35-5.31]). No correlation was found between EVT and mortality at 3 months (risk ratio, 1.34 [95% CI, 0.83-2.18]). The same overall associations were confirmed in the sensitivity analysis of studies that performed propensity score matching. CONCLUSIONS: EVT appears equivalent to BMT for patients with anterior circulation large-vessel occlusion AIS with low baseline National Institutes of Health Stroke Scale, despite the increased risk for symptomatic intracranial hemorrhage. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42022334417.

Intravenous Thrombolysis with Tenecteplase for the Treatment of Acute Ischemic Stroke.

OBJECTIVE: Intravenous thrombolysis (IVT) with tenecteplase has been associated with better clinical outcomes in acute ischemic stroke (AIS) patients with confirmed large vessel occlusions compared to IVT with alteplase. However, the utility of tenecteplase for the treatment of all AIS patients eligible for IVT has not been established. METHODS: We compared the safety and efficacy of tenecteplase versus alteplase in AIS patients by analyzing propensity score matched data from 20 centers participating in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients receiving IVT with tenecteplase were matched with up to 3 patients receiving alteplase from the same center. The primary outcome of interest was the distribution of 3-month functional outcomes. Secondary outcomes included the rates of patients with symptomatic intracranial hemorrhage (SICH) in the first 24 hours, excellent (modified Rankin Scale [mRS] score = 0-1) or good (mRS score = 0-2) functional outcome, and all-cause mortality at 3 months. RESULTS: A total of 331 tenecteplase-treated AIS patients were matched to 797 patients treated with alteplase (median age = 70 years, 43.9% women, median National Institutes of Health Stroke Scale score = 11, interquartile range = 6-17). Patients treated with tenecteplase had better 3-month functional outcomes (common odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.18-2.00) with higher odds of good functional outcome (OR = 2.00, 95% CI = 1.45-2.77) and a lower likelihood of all-cause mortality (OR = 0.43, 95% CI = 0.27-0.67) at 3 months, compared to alteplase-treated patients. No difference was found in the likelihood of the 3-month excellent functional outcomes (OR = 1.31, 95% CI = 0.96-1.78) and 24-hour SICH (1.0% vs 1.3%, OR = 0.72, 95% CI = 0.20-2.64). INTERPRETATION: IVT with tenecteplase was associated with better 3-month clinical outcomes compared to IVT with alteplase in AIS patients, with no increased risk of symptomatic intracranial bleeding. ANN NEUROL 2022;92:349-357.

Bilateral dural arteriovenous fistula diagnosed with neurovascular ultrasonography.

BACKGROUND: Intracranial dural arteriovenous fistulas (dAVFs) are pathological anastomoses between meningeal arteries and dural venous sinuses or cortical veins. Diagnosis of dAVFs can be challenging due to their broad range of clinical manifestations and the lack of specificity in their symptoms. We present a rare case of a patient with bilateral dAVFs, who was referred to our department for carotid doppler ultrasonography/transcranial color Doppler. CASE REPORT: A 67-year-old man was referred by his treating physician for neurovascular ultrasonography due to vision impairment associated with papilledema of both eyes. On ultrasound examination both external carotid arteries showed a "pseudo-internalization" pattern with high end-diastolic velocities and reduced resistance indices. Subsequent magnetic resonance and digital subtraction angiography revealed dAVF of both transverse sinuses, with occipital and medial meningeal arteries as feeders. CONCLUSIONS: Neurovascular sonography may serve as a screening and follow-up tool when a DAVF in the transverse sinus/sigmoid sinus is suspected.

Intravenous thrombolysis for acute ischemic stroke: why not?

PURPOSE OF REVIEW: The aim of this study was to summarize available evidence regarding the safety and efficacy of intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with specific comorbidities and potential contraindications to systemic reperfusion therapy. Recent advances in IVT implementation in wake-up stroke and in extended time window using advanced neuroimaging will also be highlighted. RECENT FINDINGS: Despite theoretical concerns of a higher bleeding risk with IVT, there are no data showing increased risk of symptomatic intracerebral haemorrhage (sICH) in patients with stroke mimics, including seizures, increasing age and dual antiplatelet pretreatment. In addition, recent randomized evidence allows us to expand the time window of IVT for AIS using advanced neuroimaging both in wake-up stroke patients and in patients presenting within 4.5-9 h from symptom onset fulfilling certain neuroimaging criteria (based on DWI/FLAIR mismatch or perfusion mismatch). SUMMARY: IVT is a highly effective systemic reperfusion therapy that counts 25 years of everyday clinical experience but still presents several challenges in its application. Appropriate patient selection and adherence to rt-PA protocol is paramount in terms of safety. The effort to simplify the indications, expand the therapeutic time window and eliminate specific initial contraindications is continuously evolving.

Hereditary cerebral amyloid angiopathy mimicking CADASIL syndrome.

BACKGROUND: Small vessel disease (SVD), and most specifically hereditary forms like CADASIL and cerebral amyloid angiopathy (hCAA), are conditions of increasing clinical importance. We report a rare case of hCAA in a Greek family that presented with a CADASIL clinical and neuroimaging phenotype. METHODS: A 65-year-old man was admitted with recurrent transient episodes of right leg numbness. The patient's medical history started at the age of 50 years with depression and behavioral disorders. His family history was positive for stroke (father), dementia (father and brother), migraine (daughter) and depression (father and daughter). RESULTS: Neurological examination disclosed anomic aphasia with severely impaired cognitive status, and brisk reflexes. Brain computed tomography and magnetic resonance imaging showed CADASIL-like leukoencephalopathy (hyperintense lesions in bilateral temporopolar area, external capsule, thalami, centrum semiovale and superior frontal regions) with occipital calcifications and cerebral microbleeds. Screen for variants in NOTCH3 gene was negative. Exome sequencing revealed a novel pathogenic mutation for hCAA. CONCLUSIONS: We report a novel amyloid precursor protein mutation which results in a CADASIL-like clinical phenotype (progressive cognitive and motor decline, stroke, migraine and behavioral disorders) and CADASIL-leukoencephalopathy coupled with occipital calcifications. Earlier recognition and swift hCAA diagnosis may prompt rational preventive and potential disease-modifying interventions.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.

Eligibility for intravenous thrombolysis in acute ischemic stroke patients presenting in the 4.5-9 h window.

PURPOSE: Recent randomized-controlled clinical trials have provided preliminary evidence for expanding the time window of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients by applying certain neuroimaging criteria. We prospectively assessed the potential eligibility for IVT in the extended time window (4.5-9 h) among consecutive AIS patients treated in a comprehensive stroke center during a nine-month period. METHODS: Potential eligibility for IVT in the extended time window was evaluated by using inclusion criteria from the EXTEND trial. All patients were underwent baseline emergent neurovascular imaging using either computed tomography angiography/computed tomography perfusion (CTA/CTP) or magnetic resonance angiography/magnetic resonance perfusion (MRA/MRP). Images were post processed by the automated software RAPID. RESULTS: Our study population consisted of 317 AIS patients, and, among them, 31 (9.8 %) patients were presented in the time window of 4.5-9 h. Seven patients (2.2 %) fulfilled the EXTEND neuroimaging criteria. Four patients (1.3 %) were treated with IVT because they fulfilled both clinical and neuroimaging EXTEND criteria. Patients eligible for EXTEND neuroimaging criteria had no ischemic core lesion, whereas the mean volume of critical hypoperfusion was relatively small (17.0 ± 11.8 ml). There was no hemorrhagic complication in any of the patients treated with IVT. The median mRS score at three months was 0 (range: 0-3) among patients who were eligible for EXTEND neuroimaging criteria. CONCLUSION: Our everyday clinical practice experience suggests 9.8 % of consecutive AIS patients present in the 4.5-9 h window and 2.2 % adhere to EXTEND neuroimaging eligibility criteria for IVT. Only 1.3% of AIS is eligible for IVT according to EXTEND neuroimaging and clinical eligibility criteria.

Ultrasound Assessment of Extracranial Carotids and Vertebral Arteries in Acute Cerebral Ischemia.

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications.

Combined brain and heart magnetic resonance imaging in systemic vasculitides: fiction or real need?

Systemic vasculitides (SVs) is a group of diseases characterised by inflammation/necrosis of the blood vessel wall in various organs. Simultaneous brain and heart involvement is a cause of increased morbidity/mortality in SV. We aimed to present evidence of concurrent brain/heart involvement in SV and the role of a combined brain/heart magnetic resonance imaging (MRI) in their risk stratification. Cerebral vasculitis (CV) can be presented as focal deficits, seizures, headache, neuropsychiatric manifestations or cognitive dysfunction and cardiovascular disease (CVD) as myocardial/vascular inflammation, perfusion/function defects and fibrosis. MRI is a non-invasive, non-radiating technique that allows the reliable identification of intraparenchymal brain lesions and the detection of myocardial/vascular inflammation and fibrosis. However, its use in SV is currently hampered by high cost, lack of availability/expertise and lack of awareness among the clinicians. Although there are no clinical data supporting the combined use of brain/heart MRI in asymptomatic SV, it would be called for in cases with clinical suspicion of brain/heart involvement, especially in those at high risk for CVD/stroke such as SLE/APS. Furthermore, it may be of value in SV with multi-organ involvement, cognitive dysfunction or other neuropsychiatric symptoms with concurrent cardiac involvement, presenting as typical or atypical symptoms with normal routine cardiac evaluation, new onset of arrhythmia and/or HF.

ANCA-Negative Churg-Strauss Syndrome Presenting as Acute Multiple Cerebral Infarcts: A Case Report.

Eosinophilic granulomatosis with polyangiitis (EGPA, previously named Churg-Strauss syndrome) is a form of necrotizing vasculitis occurring in patients with asthma and eosinophilia. Ischemic stroke is a relatively rare complication of the disease. We report a case of a 63-year-old woman with multiple embolic infarcts, hypereosinophilia (for >7 years), and skin rash. Elevated cardiac enzymes and cardiac magnetic resonance imaging were consistent with endomyocarditis. The simultaneous presence of history of asthma, sinusitis, hypereosinophilia, and vasculitis led to the diagnosis of EGPA. This case contributes to the recent debate of the 2 possible presentations of the disease according to the ANCA (antineutrophil cytoplasmic antibodies) status. We furthermore underscore the need for careful differential diagnosis of the "ANCA negative" cases with persistent hypereosinophilia from the idiopathic hypereosinophilic syndrome.

The Pathophysiological Mechanism Is an Independent Predictor of Long-Term Outcome in Stroke Patients with Large Vessel Atherosclerosis.

BACKGROUND: Etiopathological mechanisms underlying ischemic stroke play a crucial role in long-term prognosis. We aimed to investigate the association between the mechanism of stroke due to large vessel disease, and long-term outcome. METHODS: All consecutive patients registered in the Athens Stroke Registry with atherosclerotic stroke between 1993 and 2010 were included in the analysis. The patients were subdivided into 3 groups according to the presumed underlying mechanism: low-flow infarcts, artery-to-artery embolism, and intrinsic atherosclerosis. They were followed up for up to 10 years or until death. The end points of the study were 10-year all-cause mortality, stroke recurrence, and composite cardiovascular events. RESULTS: Five hundred two patients were classified as follows: 156 (31%) as low-flow (watershed) strokes, 256 (51%) as artery-to-artery embolic strokes, and 90 (18%) as intrinsic atherosclerotic strokes. The cumulative probability of 10-year mortality rate was similar between groups of patients with different stroke mechanisms: 49.9% (95% confidence interval [CI], 38.5-61.3) for patients with low-flow mechanism, 47.6% (95% CI, 39.4-55.8) for patients with artery-to-artery embolism, and 48.5% (95% CI, 34.0-63.0) for patients with intrinsic atherosclerosis. Patients in the intrinsic atherosclerosis group had significantly higher risks of recurrence (adjusted hazard ratio [HR] = 2.1; 95% CI, 1.19-3.73) compared with those in the artery-to-artery embolism group. Moreover, patients in the intrinsic atherosclerosis and low-flow groups had significantly higher risks of composite cardiovascular events compared with those in the artery-to-artery embolism group (adjusted HR = 1.94; 95% CI, 1.26-3.00; and adjusted HR = 1.64; 95% CI, 1.13-2.38, respectively). CONCLUSION: Low-flow and intrinsic atherosclerosis strokes are associated with a high risk for future cardiovascular events and stroke recurrence. However, long-term mortality is similar across different subgroups.

Heart failure and stroke: The underrepresentation of the heart failure with preserved ejection fraction subtype in randomized clinical trials of therapeutic anticoagulation.

Heart failure (HF) is an important comorbidity for patients with ischemic stroke, present in 11 %-18 % of patients, and may also independently increase the risk of first-ever and recurrent ischemic stroke. HF is categorized based on ejection fraction (EF) into HF with reduced (HFrEF), mildly-reduced (HFmrEG) and preserved ejection fraction (HFpEF), with the efficacy of HF therapies differing between the three subcategories. Despite this classification, the incidence, recurrence rates and outcomes of ischemic stroke do not appear to differ significantly between the three subtypes, even when considering the concurrent presence of atrial fibrillation. However, several randomized-controlled clinical trials of anticoagulation defined HF based on reduced EF, inevitably excluding a large proportion of patients with HFpEF. This exclusion is significant considering marked differences between heart failure phenotypes. Such discrepancies raise concerns about the broad applicability of the results of these studies, including those of primary or secondary stroke prevention in HF. Future trials should include both patients with HFrEF and HFpEF to evaluate the safety and efficacy of antiocoagulation therapies in primary and secondary stroke prevention across the spectrum of the EF.

Overview of systematic reviews comparing endovascular to best medical treatment for large-vessel occlusion acute ischaemic stroke: an umbrella review.

Background: The literature on endovascular treatment (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) has been rapidly increasing after the publication of positive randomized-controlled clinical trials (RCTs) and a plethora of systematic reviews (SRs) showing benefit compared to best medical therapy (BMT) for LVO. Objectives: An overview of SRs (umbrella review) and meta-analysis of primary RCTs were performed to summarize the literature and present efficacy and safety of EVT. Design and methods: MEDLINE via Pubmed, Embase and Epistemonikos databases were searched from January 2015 until 15 October 2023. All SRs of RCTs comparing EVT to BMT were included. Quality was assessed using Risk of Bias in Systematic Reviews scores and the RoB 2 Cochrane Collaboration tool, as appropriate. GRADE approach was used to evaluate the strength of evidence. Data were presented according to the Preferred Reporting Items for Overviews of Reviews statement. The primary outcome was 3-month good functional outcome [modified Rankin scale (mRS) score 0-2]. Results: Three eligible SRs and 4 additional RCTs were included in the overview, comprising a total of 24 RCTs, corresponding to 5968 AIS patients with LVO (3044 randomized to EVT versus 2924 patients randomized to BMT). High-quality evidence shows that EVT is associated with an increased likelihood of good functional outcome [risk ratio (RR) 1.78 (95% confidence interval (CI): 1.54-2.06); 166 more per 1000 patients], independent ambulation [mRS-scores 0-3; RR 1.50 (95% CI: 1.37-1.64); 174 more per 1000 patients], excellent functional outcome [mRS-scores 0-1; RR 1.90 (95% CI: 1.62-2.22); 118 more per 1000 patients] at 3 months. EVT was associated with reduced 3-month mortality [RR 0.81 (95% CI: 0.74-0.88); 61 less per 1000 patients] despite an increase in symptomatic intracranial haemorrhage [sICH; RR 1.65 (95% CI: 1.23-2.21); 22 more per 1000 patients]. Conclusion: In patients with AIS due to LVO in the anterior or posterior circulation, within 24 h from symptom onset, EVT improves functional outcomes and increases the chance of survival despite increased sICH risk. Registration: PROSPERO Registration Number CRD42023461138.