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Background: Little is known on the role of mismatch profile in patients undergoing early endovascular treatment (EVT). We aimed to describe pretreatment perfusion parameters and mismatch profiles in anterior circulation large vessel occlusion acute ischemic stroke undergoing EVT in the early time window and assess their association with time from stroke onset and outcomes. Methods: Retrospective single-center study, including early (s [for parameters] or χ 2 for trend [for profiles]) and association with modified Rankin Scale score >2, symptomatic intracranial hemorrhage, and mortality (multivariate regression analyses [each parameter/profile entered into a separate logistic regression model, adjusted for baseline variables associated with each outcome in the univariate analysis at the P Results: Among 357 patients, unfavorable mismatch profiles ranged from 21% to 60%, depending on the criterion, and were not correlated with time from stroke onset ( P =0.490). All individual perfusion parameters and unfavorable mismatch profiles were associated with poor functional outcome: ischemic core volume adjusted odds ratio (aOR), 1.49 ([95% CI, 1.13–1.97] P =0.005); penumbral volume aOR, 0.30 ([95% CI, 0.10–0.84] P =0.022); mismatch ratio aOR, 0.67 ([95% CI, 0.50–0.90] P =0.007); EXTEND-IA aOR, 2.61 ([95% CI, 1.23–5.51] P =0.012); SWIFT PRIME aOR, 2.50 ([95% CI, 1.30–4.57] P =0.006); DEFUSE 3 aOR, 2.28 ([95% CI, 1.14–4.57] P =0.020); and DAWN aOR, 4.19 ([95% CI, 2.13–8.26] P P =0.008 and aOR, 2.83 [95% CI, 1.09–7.36]; P =0.033) and death (aOR, 3.26 [95% CI, 1.33–8.02]; P =0.010 and aOR, 2.52 [95% CI, 1.10–5.82]; P =0.030). Conclusions: Pretreatment perfusion parameters and mismatch profiles in early EVT-treated patients were not correlated with time from stroke onset but were independently associated with functional outcome. Mismatch assessment in the early time window may improve EVT patient selection, independently of onset-to-treatment time.

Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown. Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0–2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0–1), symptomatic intracranial hemorrhage, and early neurological deterioration. Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63–82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4–10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66–1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95–1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35–4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64–3.84]; P Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Background. Effective treatment of acute ischemic stroke requires reperfusion of salvageable tissue. We investigated the predictors of penumbra salvage (PS) and infarct growth (IG) in a large cohort of stroke patients. Methods. In the ASTRAL registry from 2003 to 2016, we selected middle cerebral artery strokes

We report the case of a 34-year-old female patient complaining of headaches 1 day after childbirth, initially interpreted as postdural puncture headache (PDPH) and treated successfully with an epidural blood patch. Five days later, she presented with an acute proportional right sensorimotor hemisyndrome and a new-onset left-sided headache, attributed to a venous stroke from left-sided cerebral sinus venous thrombosis (CSVT). Simultaneously, we found radiologic signs of reversible cerebral vasoconstriction syndrome (RCVS), considered asymptomatic. We administered anticoagulant therapy to the patient, and she showed full motor recovery at 3-month clinical follow-up. PDPH, CSVT, and RCVS are well-known neurologic complications during the peripartum period. All 3 conditions present with headaches, and headache features may overlap, masking co-occurrence and making accurate diagnosis (differentiation) of these diseases difficult. Each disease can potentially lead to disabling deficits, but all respond to specific treatment. Knowledge of the causes of headaches in the peripartum period, their specific clinical characteristics, and potential complications helps to prioritize and interpret diagnostic tests to offer appropriate therapy.

Background and purpose: Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study-level meta-analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. Methods: We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0-2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). Results: Twelve studies with a total of 679 patients were included in the meta-analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83-70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35-55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30-20.93) and 12.3% (95% CI 8.64-17.33). sICH occurred in 4.2% (95% CI 2.47-7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75-5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. Conclusions: Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials. info:eu-repo/semantics/publishedVersion

In-hospital strokes (IHS) are associated with longer diagnosis times, treatment delays and poorer outcomes. Strokes occurring in the stroke unit have seldom been studied. Our aim was to assess the management of in-stroke-unit ischaemic stroke (ISUS) by analysing ISUS characteristics, delays in diagnosis, treatments and outcomes.Consecutive patients from the Acute Stroke Registry and Analysis of Lausanne (ASTRAL), from January 2003 to June 2019, were classified as ISUS, other-IHS or community-onset stroke (COS). Baseline and stroke characteristics, time to imaging and time to treatment, missed treatment opportunities, treatment rates and outcomes were compared using multivariate analysis with adjustment for relevant clinical, imaging and laboratory data available in ASTRAL.Amongst the 3456 patients analysed, 138 (4.0%) were ISUS, 214 (6.2%) other-IHS and 3104 (89.8%) COS. In multivariate analysis, patients with ISUS more frequently had known stroke onset time than other-IHS (adjusted odds ratio [aOR] 2.44; 95% confidence interval [CI] 1.39-4.35) or COS (aOR 2.56; 95% CI 1.59-4.17), had fewer missed treatment opportunities than other-IHS (aOR 0.22; 95% CI 0.06-0.86) and higher endovascular treatment (EVT) rates than COS (aOR 3.03; 95% CI 1.54-5.88). ISUS was associated with a favourable shift in the modified Rankin Scale at 3 months in comparison with other-IHS (aOR 1.73; 95% CI 1.11-2.69) or COS (aOR 1.46; 95% CI 1.00-2.12).In-stroke-unit ischaemic stroke more frequently had known stroke onset time than other-IHS or COS, fewer missed treatment opportunities than other-IHS and a higher EVT rate than COS. This readiness to identify and treat patients in the stroke unit may explain the better long-term outcome of ISUS.

Background and ObjectivesPatients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS) and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether AIS patients with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer and previously known active cancer and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups.MethodsUsing 2003-2021 data from the ASTRAL registry, we compared patients with known active cancer to patients with newly diagnosed cancer (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin Scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables.ResultsAmong 6686 patients with AIS, 362 (5.4%) had active cancer, including 102 (1.5%) with newly diagnosed cancer. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with active cancer, 152 (42.5%) AISs were classified as cancer-related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with newly diagnosed cancer had less pre-stroke disability (aOR 0.62, 95%CI 0.44-0.86) and fewer prior stroke/TIA events (aOR 0.43, 95%CI 0.21-0.88) than patients with known active cancer. 3-month mRS scores were similar between cancer groups (aOR 1.27, 95%CI 0.65-2.49), and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95%CI 1.49-43.17) and metastatic cancer (aOR 2.19, 95%CI 1.22-3.97). At 12 months, mortality risk was higher in patients with newly diagnosed cancer versus patients with known active cancer (HR 2.11, 95%CI 1.38-3.21) while recurrent stroke risk was similar between groups (aHR 1.27, 95%CI 0.67-2.43).DiscussionIn a comprehensive institutional registry spanning nearly two decades, 5.4% of patients with AIS had active cancer, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with newly diagnosed cancer had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with known active cancer.

Background: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to medical management may differ between clinician specialties. Methods: We conducted an international survey (1/1/22-3/31/22) regarding management strategies in acute BAO prior to the announcement of 2 trials indicating superiority of EVT, and compared responses between interventionalists (INT) and non-interventionalists (nINT). Selection practices for routine EVT based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINT=702), INT more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p0.05), although nINT more commonly preferred perfusion imaging (24.2% vs. 19.7%, p=0.04). Among respondents who indicated they would randomize to medical management, INT were more likely to randomize when the NIHSS was ≥10 (15.9% vs. 6.9%, p Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a patient to medical treatment. There were small differences in preference of advanced neuroimaging, although these preferences were unsupported by clinical trial data.

Introduction: Endovascular treatment (EVT), in particular mechanical thrombectomy, has dramatically improved the clinical outcome of patients with large vessels occlusion (LVO) of the anterior circulation. In contrast, the benefits of EVT cannot be applied to lacunar strokes (LS). The absence of a LVO in LS has been historically associated with a more favorable outcome, but in the new era of EVT, this assumption may not be correct anymore. We aimed to test the general assumption that LS have a better prognosis than other stroke subtypes, and analyze the outcome of LS treated with IVT as compared to strokes with LVO treated with IVT and/or mechanical thrombectomy in the multicentric Swiss Stroke Registry. Methods: retrospective propensity score matching analysis of patients from the Swiss stroke registry (SSR) with lacunar stroke treated with thrombolysis versus LVO of the medial cerebral artery treated with EVT (with or without thrombolysis). Primary endpoint was a shift analysis of mRs at 90 days after stroke. Secondary outcomes were favorable functional outcome (mRS 0-1), independence (mRS 0-2), survival with high disability (mRS 3-5) and mortality (mRS 6) at 90 days. Results: From 13'227 patients, the propensity score method matched (sex, age, NIHSS, time to treatment, prior anticoagulation, pre-stroke modified Rankin Score, mRs) 538 patients (269 in each group. There was no difference between groups in mRs shift analysis at 90 days after stroke (OR=0.99, 95%CI=0.73-1.35, p=0.952). There was also no significant difference in mRS 0-1 (59.9% vs 55.8% respectively; OR=0.79, 95%CI=0.55-1.16, p=0.75). LS+IVT patients showed a non-significant trend towards mRS 3-5 (OR=1.23, 95%CI=0.78-1.94, p=0.38), while patients treated with EVT had a slightly, non-significant, higher mortality (6.3% vs 1.9%, p=0.38). Conclusions: Lacunar strokes - which cannot directly benefit from thrombectomy therapy - when treated with IVT and matched on key prognostic variables, seem to have similar outcomes as LVO strokes treated with EVT. This observation confirms that lacunar stroke is not a benign entity and therefore suggests that reperfusion therapy should be addressed with the same intensity as LVO stroke.

© 2023 American Society of Neuroimaging., Background and purpose: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. Methods: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. Results: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). Conclusions: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.

Background and ObjectivesCurrent guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO.MethodsWe analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6–24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days).ResultsOf 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72–87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13–22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78–8.79 and OR 3.10, 95% CI 1.20–7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97–6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86–0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75–0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR.DiscussionIn patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management.Classification of EvidenceThis investigation's results provide Class III evidence that in patients with preexisting disability presenting 6–24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function.

Background: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. Methods: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those Results: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio adjusted 1.14 [0.83–1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio adjusted 3.77 [3.14–4.53]) and poor functional outcome (odds ratio adjusted 2.63 [2.13–3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. Conclusions: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Introduction: Migraine with aura (MA) accounts for up to 10% of “stroke mimics” and can present cerebral perfusion abnormalities. We aimed to compare perfusion-CT (PCT) findings in acute-onset MA mimicking an ischemic stroke with those observed in transient ischemic attack (TIA). Methods: We retrospectively studied patients admitted to our hospital between 2002 and 2014 with suspicion of acute ischemic stroke, having PCT and receiving a final diagnosis of MA. We visually assessed PCT for the presence and extent of focal hypoperfusion (FHP). MA patients with FHP were compared with consecutive TIA patients showing FHP. We performed both qualitative and quantitative analysis of PCT. Results: Of 47 patients with MA (median age = 33 years, 55% females), 16 (34%) displayed FHP. Compared to MA patients without FHP, MA patients with FHP had similar headaches and aura features, but a less frequent history of MA ( p = 0.010). Compared to 74 TIA patients with FHP (median age = 69 years, 43% females), MA patients with FHP showed hypoperfusion that more frequently involved adjacent vascular territories or a whole hemisphere ( p Conclusion: Focal perfusion abnormalities in acute MA often involve adjacent vascular territories and hypoperfusion is less pronounced than in TIA. MA can be best differentiated from TIA by a smaller rMTT increase.

ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.

Background and Purpose: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention. Methods: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early ( Results: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, P adj =0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, −2.5 versus 2, P adj =0.01). Conclusions: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications.

BACKGROUND AND PURPOSE: Both ASPECTS and core volume on CTP are used to estimate infarct volume in acute ischemic stroke. To evaluate the potential role of ASPECTS for acute endovascular treatment decisions, we studied the correlation between ASPECTS and CTP core, depending on the timing and the presence of large-vessel occlusion. MATERIALS AND METHODS: We retrospectively reviewed all MCA acute ischemic strokes with standardized reconstructions of CTP maps entered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) registry. Correlation between ASPECTS and CTP core was determined for early (

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA 2 DS 2 -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥ 3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥ 4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. Results: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42–2.16]; P P =0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20–2.15]; P =0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59–4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30–3.75]), dependency or death (OR, 1.42 [0.91–2.23]), or mortality (OR, 1.65 [0.94–2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76–5.04]), dependency or death (OR, 1.49 [1.07–2.07]), and mortality (OR, 1.65 [1.11–2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73–4.29]). Conclusions: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Most case series of patients with ischemic stroke (IS) and COVID-19 are limited to selected centers or lack 3-month outcomes. The aim of this study was to describe the frequency, clinical and radiological features, and 3-month outcomes of patients with IS and COVID-19 in a nationwide stroke registry. From the Swiss Stroke Registry (SSR), we included all consecutive IS patients ≥18 years admitted to Swiss Stroke Centers or Stroke Units during the first wave of COVID-19 (25 February to 8 June 2020). We compared baseline features, etiology, and 3-month outcome of SARS-CoV-2 polymerase chain reaction-positive (PCR+) IS patients to SARS-CoV-2 PCR- and/or asymptomatic non-tested IS patients. Of the 2341 IS patients registered in the SSR during the study period, 36 (1.5%) had confirmed COVID-19 infection, of which 33 were within 1 month before or after stroke onset. In multivariate analysis, COVID+ patients had more lesions in multiple vascular territories (OR 2.35, 95% CI 1.08-5.14, p = 0.032) and fewer cryptogenic strokes (OR 0.37, 95% CI 0.14-0.99, p = 0.049). COVID-19 was judged the likely principal cause of stroke in 8 patients (24%), a contributing/triggering factor in 12 (36%), and likely not contributing to stroke in 13 patients (40%). There was a strong trend towards worse functional outcome in COVID+ patients after propensity score (PS) adjustment for age, stroke severity, and revascularization treatments (PS-adjusted common OR for shift towards higher modified Rankin Scale (mRS) = 1.85, 95% CI 0.96-3.58, p = 0.07). In this nationwide analysis of consecutive ischemic strokes, concomitant COVID-19 was relatively rare. COVID+ patients more often had multi-territory stroke and less often cryptogenic stroke, and their 3-month functional outcome tended to be worse.

BACKGROUND AND PURPOSE Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. METHODS We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. RESULTS Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. CONCLUSIONS This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.

Background An acute ischemic stroke carries a substantial risk of further recurrences. We aimed at developing and validating a prognostic tool to predict one-year stroke recurrence after acute ischemic stroke. Methods An integer score was derived by Cox regression analysis on a hospital-referred cohort of 3246 acute ischemic stroke patients from Switzerland, and tested for external validity in three similar independent cohorts from Athens ( n = 2495), Milan ( n = 1279), and Helsinki ( n = 714) by means of calibration and discrimination. Results In the derivation cohort, the recurrence rate was 7% ( n = 228/3246). We developed a nine-point score comprising: previous stroke or transient ischemic attack (1-point), stroke mechanism (small vessel disease and unknown mechanism: 0-points; rare stroke mechanism: 3-points; other mechanisms: 1-point), pre-stroke antiplatelets (1-point), active malignancy (2-points), chronic cerebrovascular lesions on imaging (1-point) and absence of early ischemic changes on first imaging (1-point). In the derivation cohort, the one-year risk of re-stroke was 3.0% (95%CI 1.9–4.1) in 932 (29%) patients with a score 0–1, 7.2% (6.1–8.3) in 2038 (63%) with a score 2–4, and 19.2% (14.6–23.9) in 276 (8%) with a score ≥ 5. The score calibrated well in the Athens (recurrences = 208/2495), but not in the Helsinki (recurrences = 15/714) or Milan (recurrences = 65/1279) cohorts. The AUC was 0.67 in the derivation cohort, and 0.56, 0.70, and 0.63 in the Athens, Helsinki, and Milan cohorts, respectively. Conclusion We developed a score to predict one-year stroke recurrence risk in patients with acute ischemic stroke. Since the score was not completely validated when applied to external datasets where it displayed poor to fair calibration and discrimination, additional efforts are required to ameliorate our accuracy for predicting stroke recurrence, by better refining this prognostic tool or developing new ones. Clinical and radiological markers of established cerebrovascular disease and stroke etiology were better predictors than the usual demographic vascular risk factors.

Background and aims Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. Methods We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Results Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; −1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; −3 points for left ventricular ejection fraction 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. Conclusions The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. Clinical trial registration URL: https://www.clinicaltrials.gov / Unique identifier: NCT02766205.

Background and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

Background and Purpose— The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0–4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods— In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results— In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0–4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37–3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%–73.3%). Conclusions— The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT—as compared to no-IVT—may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score 7d ) and 3-month modified Rankin Scale score 0 to 1. Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07–3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75–2.23]; P =0.37; modified Rankin Scale score of 0–1: adjusted odds ratio, 1.1 [95% CI, 0.6–2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9–10.1) versus 20.4 hours (interquartile range, 7.8–34.4), respectively, P Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END—particularly END due to artery-to-artery embolism—occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

Background Posterior circulation and anterior circulation strokes share many clinical, pathogenetic and radiological features, although some clinical signs are highly specific to posterior circulation strokes. Arterial stenosis and occlusions occur in significant numbers in both acute posterior circulation and anterior circulation strokes, making them good candidates for endovascular treatment. Among posterior circulation strokes, basilar artery occlusions stand out because of the diagnostic and acute treatment challenges. Methods We reviewed the literature on clinical stroke syndromes and neuroimaging findings and systematically describe for each anatomical site of stroke the detailed clinical and radiological information (anatomical representation, diffusion weighted imaging and angiographic sequences). The principles of neuroimaging of posterior circulation strokes and the prognosis for each stroke localization are also discussed. Review summary Stroke syndromes in the territories of the vertebral, basilar, cerebellar, and posterior cerebral arteries are presented. Features typical of posterior circulation strokes are highlighted, including patterns of basilar artery occlusions. Clinical severity and prognosis of posterior circulation strokes are highly variable, and given that they are more difficult to detect on CT-based neuroimaging, magnetic resonance imaging is the technique of choice in suspected posterior circulation strokes. Rapid identification of arterial occlusion patterns may provide prognostic information and support acute revascularization decisions. Conclusions Posterior circulation stroke syndromes tightly reflect lesion localization and arterial occlusion patterns. Although many clinical and pathogenetic features are similar to anterior circulation strokes, notable differences exist in terms of clinical presentation, stroke mechanism, prognosis, and response to acute recanalization.

Certain drugs may increase the risk of ischemic stroke (IS). Our goal was to review associations between frequently used drugs and IS. We created an initial list of frequently used drugs to search Pubmed/MEDLINE from 1966 to 2020 and reviewed phase III and IV data, case series, and drug authorities’ safety warnings to assess a potential association with IS. Drugs were grouped according to the World Health Organization Anatomical Therapeutic Chemical Classification System. Predefined criteria were applied to establish a level of evidence for an association, from A (high level of evidence of association) to E (high level of evidence of absence of association). In addition, we assessed relative risks and reviewed potential mechanisms of IS facilitation. We assessed 81 drugs or drug classes from 11 World Health Organization Anatomical Therapeutic Chemical Groups. We identified a high level of association for erythropoietin, combined contraceptives, oral estrogen replacement therapy, bevacizumab, tamoxifen, and antipsychotics and a moderate level for ponatinib, nilotinib, darunavir, and gonadotropin-releasing hormone agonists. Drug dose and treatment duration may modify the risk. For a substantial number of drugs, we found no association, and for others, there were insufficient data to categorize risk. We identified a high level of association of IS with a limited number of drugs, a potential association with some, and a lack of data for others. The summarized information may help clinicians to estimate the contribution of a drug to an IS, to better assess drug benefit-risk ratios, and to support decisions about using specific drugs.

Background and Purpose— Early arterial recanalization is a strong determinant of prognosis in acute ischemic stroke. Nevertheless, reocclusion can occur after initial recanalization. We assessed associated factors and long-term prognosis of reocclusion after successful mechanical thrombectomy (MT). Methods— From the prospectively constructed Acute Stroke Registry and Analysis of Lausanne cohort, we included consecutive patients with anterior and posterior circulation strokes treated by successful MT (modified treatment in cerebral infarction 2b-3) and with 24-hour vascular imaging available. Reocclusion at this time-point was defined as new intracranial occlusion within an arterial segment recanalized at the end of MT. Through multivariate logistic regression, we investigated associated factors and 3-months outcome. In a 4:1 matched-cohort, we also assessed the role of residual thrombus or stenosis on post-recanalization angiographic images as potential predictor of reocclusion. Results— Among 473 patients with successful recanalization, 423 (89%) were included. Of these, 28 (6.6%) had 24-hour reocclusion. Preadmission statin therapy (aOR [adjusted odds ratio], 0.27; 95% CI, 0.08–0.94), intracranial internal carotid artery occlusion (aOR, 3.53; 95% CI, 1.50–8.32), number of passes (aOR, 1.31; 95% CI, 1.06–1.62), transient reocclusion during MT (aOR, 8.55; 95% CI, 2.14–34.09), and atherosclerotic cause (aOR, 3.14; 95% CI, 1.34–7.37) were independently associated with reocclusion. In the matched-cohort analysis, residual thrombus or stenosis was associated with reocclusion (aOR, 15.6; 95% CI, 4.6–52.8). Patients experiencing reocclusion had worse outcome (aOR, 5.0; 95% CI, 1.2–20.0). Conclusions— Reocclusion within 24-hours of successful MT was independently associated with statin pretreatment, occlusion site, more complex procedures, atherosclerotic cause, and residual thrombus or stenosis after recanalization. Reocclusion impact on long-term outcome highlights the need to monitor and prevent this early complication.

Efficacy and safety of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) due to intracranial artery dissection (IAD) are currently not established. We aimed to present a single-center experience on IAD-related AIS treated by IVT. We selected all consecutive patients with IAD-related AIS treated by IVT from a prospectively constructed single-center acute stroke registry from 2003 to 2017. We reviewed demographical, clinical and neuroimaging data and recorded hemorrhagic complications, mortality within 7 days and modified Rankin Scale at 3-months. Out of 181 AISs related to cervicocephalic dissections, 10 (5.5%) were due to IAD and five of these patients received IVT. Among these five patients, median age was 62 years; hypertension and dyslipidemia were the most frequent vascular risk factors. IAD locations were distal internal carotid artery, middle cerebral artery (M1), anterior cerebral artery (A2), and, in two cases, the basilar artery. All anterior circulation IADs were occlusive or subocclusive, while the two basilar artery IADs caused arterial stenosis. After IVT, there were no subarachnoid or symptomatic intracranial hemorrhages. One patient had an asymptomatic hemorrhagic infarct type 1. Two patients died within 7 days from ischemic mass effect. The other three patients had favorable clinical outcomes at 3-months. In this small single-center case series of IAD-related AIS, thrombolysis seemed relatively safe. However, IVT efficacy and the likelihood of arterial recanalization are still uncertain in this context. Further studies are needed to assess the safety and efficacy of IVT in these patients.