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Occlusive and nonocclusive cervicocephalic thrombi can be encountered during neurovascular imaging in patients with acute ischemic stroke. Radiographic and morphological characteristics on basic and advanced imaging modalities can be important clues towards determination of pathomechanism and the choice of acute and subacute treatment modalities. The aim of this review article is to evaluate the epidemiology, radiographic properties, histologic clot composition of cervicocephalic arterial thrombi, and its response to various medical and endovascular therapy modalities. Future studies are needed to derive and validate a classification system for extracranial and intracranial partially occlusive thrombi to enable further testing of various stroke treatment and prevention strategies in these patients.

© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.562 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made., Objective: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. Methods: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. Results: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). Conclusions: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573., This research was funded by The Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005) and the Dr. C. J. Vaillant Foundation.

Background and ObjectivesAcute arterial ischemic stroke (AIS) has been reported as a rare adverse event following coronavirus disease 2019 (COVID-19) vaccination with messenger RNA (mRNA) or viral vector vaccines. However, data are sparse regarding the risk of postvaccination AIS and its potential association with thrombotic-thrombocytopenia syndrome (TTS).MethodsA systematic review and meta-analysis of randomized controlled clinical trials (RCTs), pharmacovigilance registries, registry-based studies, observational cohorts, and case-series was performed with the aim to calculate the following: (1) the pooled proportion of patients presenting with AIS following COVID-19 vaccination; (2) the prevalence of AIS after mRNA and vector-based vaccination; and (3) the proportion of TTS among postvaccination AIS cases. Patient characteristics were assessed as secondary outcomes.ResultsTwo RCTs, 3 cohort studies, and 11 registry-based studies comprising 17,481 AIS cases among 782,989,363 COVID-19 vaccinations were included in the meta-analysis. The pooled proportion of AIS following exposure to any COVID-19 vaccine type was 4.7 cases per 100,000 vaccinations (95% CI 2.2–8.1; I2 = 99.9%). The pooled proportion of AIS following mRNA vaccination (9.2 cases per 100,000 vaccinations; 95% CI 2.5–19.3; I2 = 99.9%) did not differ compared with adenovirus-based vaccination (2.9 cases per 100,000 vaccinations; 95% CI 0.3–7.8; I2 = 99.9%). No differences regarding demographics were disclosed between patients with AIS following mRNA-based or vector-based vaccination. The pooled proportion of TTS among postvaccination AIS cases was 3.1% (95% CI 0.7%–7.2%; I2 = 78.8%).DiscussionThe pooled proportion of AIS following COVID-19 vaccination is comparable with the prevalence of AIS in the general population and much lower than the AIS prevalence among severe acute respiratory syndrome coronavirus 2–infected patients. TTS is very uncommonly reported in patients with AIS following COVID-19 vaccination.

Background and ObjectivesProlonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence.MethodsWe searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT).ResultsWe included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54–6.03; RR 2.16, 95% CI 1.66–2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57–2.70; RR 2.01, 95% CI 1.43–2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15–0.59), but not in RCTs (RR 0.72, 95% CI 0.49–1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders.DiscussionPCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

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.

BackgroundThe periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of antithrombotics following eCAS.MethodsWe followed PRISMA guidelines and searched MEDLINE, Embase, and Scopus from January 1, 2004 to November 30, 2022 for studies evaluating eCAS in tandem occlusion. The primary endpoint was 90-day good functional outcome. Secondary outcomes were symptomatic intracerebral hemorrhage, in-stent thrombosis, delayed stent thrombosis, and successful recanalization. Meta-analysis of proportions and meta-analysis of odds ratios were implemented.Results34 studies with 1658 patients were included. We found that the use of no antiplatelets (noAPT), single antiplatelet (SAPT), dual antiplatelets (DAPT), or glycoprotein IIb/IIIa inhibitors (GPI) yielded similar rates of good functional outcomes, with a marginal benefit of GPI over SAPT (OR 1.88, 95% CI 1.05 to 3.35, Pheterogeneity=0.31). Sensitivity analysis and meta-regression excluded a significant impact of intravenous thrombolysis and Alberta Stroke Program Early CT Score (ASPECTS). We observed no increase in symptomatic intracerebral hemorrhage (sICH) with DAPT or GPI compared with noAPT or SAPT. We also found similar rates of delayed stent thrombosis across groups, with acute in-stent thrombosis showing marginal, non-significant benefits from GPI and DAPT over SAPT and noAPT.ConclusionsIn AIS due to tandem occlusion, the periprocedural antithrombotic regimen of eCAS seems to have a marginal effect on good functional outcome. Overall, high intensity antithrombotic therapy may provide a marginal benefit on good functional outcome and carotid stent patency without a significant increase in risk of sICH.

Background: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults. We aimed to determine the impact of age, gender and risk factors (including sex-specific) on CVT onset. Methods: We used data from the BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis), a multicentre multinational prospective observational study on CVT. Composite factors analysis (CFA) was performed to determine the impact on the age of CVT onset in males and females. Results: A total of 1309 CVT patients (75.3% females) aged ⩾18 years were recruited. The overall median (IQR-interquartile range) age for males and females was 46 (35–58) years and 37 (28–47) years ( p Conclusions: Women suffer CVT 9 years earlier in comparison to men. Female patients with multiple (⩾1) risk factors suffer CVT ~12 years earlier compared to those with no identifiable risk factors.

BACKGROUND We developed a prognostic score to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials.. METHODS We used data from the International CVT Consortium. We excluded patients with pre-existent functional dependency. We used logistic regression to predict poor outcome (modified Rankin Scale 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunken using Ridge regression to adjust for optimism in internal validation. RESULTS Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, we derived the SI2 NCAL2 C score utilizing the following components: absence of female Sex-specific risk factor, Intracerebral hemorrhage, Infection of the central nervous system, Neurologic focal deficits, Coma, Age, lower Level of hemoglobin (g/L), higher Level of glucose (mmol/L) at admission, and Cancer. C-statistics were 0.80 (95%CI 0.75-0.84), 0.84 (95%CI 0.80-0.88) and 0.84 (95%CI 0.80-0.88) for the poor outcome, 30 days and 1 year mortality model, respectively. Calibration plots indicated good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

© 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 ObjectivesThere is accumulating evidence supporting an association between the thrombosis and thrombocytopenia syndrome (TTS) and adenovirus vector-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yet TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.MethodsWe performed a systematic review and meta-analysis of clinical trials, cohorts, case series, and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with postvaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.ResultsSixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4,182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were included further in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95% confidence interval [CI] 36%–66%; I2 = 61%). TTS was independently associated with a higher likelihood of CVST when compared to patients without TTS with thrombotic events after vaccination (odds ratio 13.8; 95% CI 2.0–97.3; I2 = 78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95% CI 21%–36%) and 38% (95% CI 27%–49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval 10 days; 95% CI 8–12) and affected predominantly women (69%; 95% CI 60%–77%) under age 45, even in the absence of prothrombotic risk factors.DiscussionApproximately half of patients with TTS present with CVST; almost one-third of patients with TTS do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.Registration InformationThe prespecified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

Background: Mild cognitive impairment (MCI) and dementia are associated with increased age. MCI is a clinical entity described as a transitional state between normal cognition and dementia. Video games (VGs) can potentially promote cognition and functional capacity since multiple cognitive domains are recruited during gameplay. However, there is still a lack of consensus regarding the efficacy of VGs as therapeutic tools, particularly in neurodegenerative diseases. Objective: We aimed to analyze the impact of VGs on cognition and functional capacity outcomes in MCI/dementia patients. Methods: We conducted a systematic review and meta-analysis study (PROSPERO [CRD42021229445]). PubMed, Web of Science, Epistemonikos, CENTRAL, and EBSCO electronic databases were searched for RCT (2000-2021) that analyzed the impact of VGs on cognitive and functional capacity outcomes in MCI/dementia patients. Results: Nine studies were included (n = 409 participants), and Risk of Bias (RoB2) and quality of evidence (GRADE) were assessed. Data regarding attention, memory/learning, visual working memory, executive functions, general cognition, functional capacity, quality of life were identified, and pooled analyses were conducted. An effect favoring VGs interventions was observed on Mini-Mental State Examination (MMSE) score (MD = 1.64, 95%CI 0.60 to 2.69). Conclusion: Although promising, the effects observed should be interpreted with caution since serious methodological shortcomings were identified in the studies included. Nonetheless, the effect observed is higher than the minimum clinically important difference (1.4 points) established to MMSE. Future studies on the current topic urge. Recommendations for the design and conduction of cognitive RCT studies are presented.

Contains fulltext : 238007.pdf (Publisher’s version ) (Closed access) IMPORTANCE: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. OBJECTIVE: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. EXPOSURES: Diagnosis of cerebral venous sinus thrombosis. MAIN OUTCOMES AND MEASURES: Frequencies of admission thrombocytopenia (platelet count 0.4, in a subset of patients with previously collected plasma samples). RESULTS: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/μL) in 52 (6.0%), moderate (50-99 ×103/μL) in 17 (2.0%), and severe (

Neurovascular disorders is a heterogenous group of diseases, including one of the most time critical disorders in emergency medicine; stroke. Sex differences are extensively described in neurovascular disorders, ranging from differences in symptom presentation, risk factors, treatment and outcomes. For example, women with stroke, more often present with generalized weakness, reduced consciousness and headache than men. Furthermore, there are differences in risk factors, outcomes and in the effect of secondary prevention. Women have a higher risk of cerebral venous thrombosis and developing cerebral aneurysms. In general, women have been underrepresented in trials on neurovascular disorders. This chapter provides an extensive overview of sex differences in stroke in general and in the differences specially seen in ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage and in cerebral venous thrombosis.

Introduction: There is uncertainty regarding the optimal timing for initiation of oral anticoagulation in patients with acute ischemic stroke (AIS) due to atrial fibrillation (AF). Methods: We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and prospective observational studies to assess the efficacy and safety of early anticoagulation in AF-related AIS (within 1 week versus 2 weeks). A second comparison was performed assessing the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin-K antagonists (VKAs) in the two early time windows. The outcomes of interest were IS recurrence, all-cause mortality, symptomatic intracerebral haemorrhage (sICH) and any ICH. Results: Eight eligible studies (6 observational, 2 RCTs) were identified, including 5616 patients with AF-related AIS who received early anticoagulation. Patients that received anticoagulants within the first week after index stroke had similar rate of recurrent IS, sICH and all-cause mortality compared to patients that received anticoagulation within two weeks (test for subgroup differences p = 0.1677; p = 0.8941; and p = 0.7786, respectively). When DOACs were compared to VKAs, there was a significant decline of IS recurrence in DOAC-treated patients compared to VKAs (RR: 0.65; 95%CI: 0.52-0.82), which was evident in both time windows of treatment initiation. DOACs were also associated with lower likelihood of sICH and all-cause mortality. Conclusions: Early initiation of anticoagulation within the first week may have a similar efficacy and safety profile compared to later anticoagulation (within two weeks), while DOACs seem more effective in terms of IS recurrence and survival compared to VKAs. info:eu-repo/semantics/publishedVersion

Cotinine, the primary metabolite of nicotine, is currently regarded as the best biomarker of tobacco smoke exposure. We aim to assess whether cotinine levels are associated with (1) intracranial aneurysm and (2) intracranial aneurysm rupture.We performed a single-center case-control study. Cases were consecutive patients admitted with diagnosis of brain aneurysm (ruptured or unruptured). We randomly selected controls without intracranial aneurysm from the same source population that produced the cases. Smoking data were collected by questionnaire, and serum levels of cotinine were used as an objective measure of nicotine exposure. Logistic regression models were used to assess the relationship between cotinine levels and aneurysm rupture.We included 86 patients with intracranial aneurysm and 96 controls. Smoking status (p .001), cotinine levels (p = .009), and female sex (p = .006) were associated with diagnosis of intracranial aneurysm. In the multivariate analysis, controlling for sex, smoker status and age, levels of cotinine were independently associated with aneurysm rupture (OR 1.53, 95% CI 1.10-2.13, p = .012).Our results suggest that high cotinine levels in smokers with brain aneurysm are significantly associated with high rupture risk, independently of smoker status, age, and sex.

Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.

Background: Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a syndrome that mimics heparin-induced thrombocytopenia (HIT) and occurs after vaccination with adenovirus-based SARS-CoV-2 vaccines. We aimed to systematically review the incidence, clinical features, and prognosis of CVT occurring in patients with HIT. Methods: The study protocol was registered with PROSPERO (CRD42021249652). MEDLINE, EMBASE and Cochrane CENTRAL were searched up to June 1, 2021 for HIT case series including >20 patients, or any report of HIT-related CVT. Demographic, neuroradiological, clinical, and mortality data were retrieved. Meta-analysis of proportions with random-effect modeling was used to derive rate of CVT in HIT and in-hospital mortality. Pooled estimates were compared with those for CVT without HIT and HIT without CVT, to determine differences in mortality. Results: From 19073 results, we selected 23 case series of HIT (n=1220) and 27 cases of HIT-related CVT (n=27, 71% female). CVT developed in 1.6% of 1220 patients with HIT (95% CI,1.0%–2.5%, I 2 =0%). Hemorrhagic brain lesions occurred in 81.8% of cases of HIT-related CVT and other concomitant thrombosis affecting other vascular territory was reported in 47.8% of cases. In-hospital mortality was 33.3%. HIT-related CVT carried a 29% absolute increase in mortality rate compared with historical CVT controls (33.3% versus 4.3%, P P =0.046). Conclusions: CVT is a rare thrombotic manifestation in patients with HIT. HIT-related CVT has higher rates of intracerebral hemorrhage and a higher mortality risk, when compared with CVT in historical controls. The recently reported high frequency of CVT in patients with vaccine-induced thrombotic thrombocytopenia was not observed in HIT, suggesting that additional pathophysiological mechanisms besides anti-platelet factor-4 antibodies might be involved in vaccine-induced thrombotic thrombocytopenia-related CVT.

ObjectiveTo examine the incidence, characteristics, treatment, and predictors of late seizures (LS) after cerebral venous thrombosis (CVT), we described these features in a registry of 1,127 patients with CVT.MethodsWe included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with 7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS.ResultsWe included 1,127 patients with CVT. During a median follow-up of 2.0 years (interquartile range [IQR] 1.0–6.3), 123 patients (11%) experienced ≥1 LS (incidence rate for first LS 30 per 1,000 person-years, 95% confidence interval [CI] 25–35). Median time to first LS was 5 months (IQR 1–16 months). Baseline predictors of LS included status epilepticus in the acute phase (hazard ratio [HR] 7.0, 95% CI 3.9–12.6), decompressive hemicraniectomy (HR 4.2, 95% CI 2.4–7.3), acute seizure(s) without status epilepticus (HR 4.1, 95% CI 2.5–6.5), subdural hematoma (HR 2.3, 95% CI 1.1–4.9), and intracerebral hemorrhage (HR 1.9, 95% CI 1.1–3.1). Eighty-five patients (70% of patients with LS) experienced a recurrent seizure during follow-up, despite the fact that 94% received antiepileptic drug treatment after the first LS.ConclusionDuring a median follow-up of 2 years, ≈1 in 10 patients with CVT had LS. Patients with baseline intracranial bleeding, patients with acute symptomatic seizures, and those who underwent decompressive hemicraniectomy were at increased risk of developing LS. The high recurrence risk of LS justifies epilepsy diagnosis after a first LS.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has been placing an overwhelming burden on health systems, thus threatening their ability to operate effectively for acute conditions in which treatments are highly time sensitive, such as cerebrovascular disorders and myocardial infarction. As part of an effort to reduce the consequences of this outbreak on health service delivery to stroke patients, the European Stroke Organisation has undertaken a survey aimed at collecting information on the provision of stroke care during the pandemic. Methods Cross-sectional, web-based survey, conducted from 26 March through 1 April 2020 among stroke care providers, focused on reorganisation of health services, the delivery of acute and post-acute stroke care and the availability of personal protective equipment. Results A total of 426 stroke care providers from 55 countries completed the survey, most of whom worked in Europe (n = 375, 88%) and were stroke physicians/neurologists (n = 334, 78%). Among European respondents, 289 (77%) reported that not all stroke patients were receiving the usual care in their centres and 266 (71%) estimated that functional outcomes and recurrence rates of stroke patients would be negatively affected by the organisational changes caused by the pandemic. The areas considered as being most affected were acute care and rehabilitation. Most professionals had to adapt their activities and schedules and more than half reported shortage of protective equipment. Discussion Strategies to maintain availability of stroke care during the COVID-19 outbreak are crucial to prevent indirect mortality and disability due to suboptimal care. Conclusion European Stroke Organisation proposes a set of targeted actions for decision makers facing this exceptional situation.

Background and Purpose— The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods— PRIORITy-CVT (Pathophysiology of Venous Infarction – Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results— Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression ( P =0.03) and lower risk of enlargement of nonhemorrhagic lesions ( P =0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions— Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.

Introduction: High-quality evidence regarding the use of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) has been provided by recently completed randomized controlled clinical trials (RCTs). Methods: We conducted a systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of EVT in addition to best medical treatment (BMT) versus BMT alone for BAO. The random-effects model was used, while the fragility index (FI) was calculated for dichotomous outcomes of interest. Results: Four RCTs were included comprising a total of 988 patients with acute BAO (mean age: 65.6 years, 70% men, median NIHSS: 24, 39% pretreatment with intravenous thrombolysis). EVT was related to higher likelihood of good functional outcome (RR: 1.54; 95% CI: 1.16–2.05; I2 = 60%), functional independence (RR: 1.83; 95% CI: 1.08–3.08; I2 = 79%) and reduced disability at 3 months (adjusted common OR: 1.96; 95% CI: 1.26–3.05; I2 = 59%) compared to BMT alone. Despite that EVT was associated with a higher risk for symptomatic intracranial hemorrhage (RR: 7.78; 95% CI: 2.36–25.61; I2 = 0%) and any intracranial hemorrhage (RR: 2.85; 95% CI: 1.50–5.44; I2 = 16%), mortality at 3 months was lower among patients that received EVT plus BMT versus BMT alone (RR: 0.76; 95% CI: 0.65–0.89; I2 = 0%). However, sufficient robustness was not evident in any of the reported associations (FI < 10) including the overall effect regarding the primary outcome. The former associations were predominantly driven by RCTs with recruitment limited in China. Conclusions: EVT combined with BMT is associated with a higher likelihood of achieving good functional outcomes and a lower risk of death at 3 months compared to BMT alone, despite the higher risk of sICH. An individual-patient data meta-analysis is warranted to uncover and adjust for potential sources of heterogeneity and to provide further insight.

Background and Purpose: Cerebral venous sinus thrombosis (CVST) has been reported as a rare adverse event in association with thrombosis-thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Methods: We performed a systematic review and meta-analysis of investigator-initiated registries including confirmed CVST cases, with the aim to calculate (1) the odds ratio of TTS–CVST versus non-TTS–CVST after vector-based vaccines and (2) after non-vector-based vaccines, (3) the in-hospital mortality ratio of TTS–CVST compared to non-TTS–CVST; and (4) the dependency or death at discharge among TTS–CVST compared to non-TTS–CVST cases. Results: Two eligible studies were included in the meta-analysis, comprising a total of 211 patients with CVST associated with COVID-19 vaccination. Vector-based COVID-19 vaccination was associated with a higher likelihood of TTS-associated CVST than with non-TTS–CVST (OR: 52.34, 95% CI 9.58–285.98). TTS–CVST was also associated with higher likelihood of in-hospital mortality (OR: 13.29; 95% CI 3.96–44.60) and death or dependency at discharge compared to non-TTS–CVST (OR: 6.70; 95% CI 3.15–14.26). TTS–CVST was recorded with a shorter interval between vaccination and symptom onset [Mean Difference (MD):-6.54 days; 95% CI − 12.64 to − 0.45], affecting younger patients (MD:-9.00 years; 95% CI − 14.02 to − 3.99) without risk factors for thromboses (OR:2.34; 95% CI 1.26–4.33), and was complicated more frequently with intracerebral hemorrhage (OR:3.60; 95% CI 1.31–9.87) and concomitant thromboses in other sites (OR:11.85; 95% CI 3.51–39.98) compared to non-TTS–CVST cases. Conclusions: TTS–CVST following COVID-19 vaccination has distinct risk factor profile, clinical phenotype and prognosis compared to non-TTS–CVST. Further epidemiological data are required to evaluate the impact of different treatment strategies on outcome of TTS–CVST cases following COVID-19 vaccination.

Introduction: Cerebral Venous Sinus Thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of SARS-CoV-2 vaccination. The estimated background rate of CVST in adults is around 1 case per million per month, and CVST with thrombocytopenia accounts for 8% of all CVST. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. Methods: We estimated the absolute risk of any CVST, CVST with thrombocytopenia, and CVST without thrombocytopenia, within 28 days of first dose SARS-CoV-2 vaccination, using data from the European Medicines Agency’s EudraVigilance database (until 13 June 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. Results: The absolute risk of CVST within 28 days of first dose vaccination was 7.5 (95%CI 6.9-8.3), 0.7 (95%CI 0.2-2.4), 0.6 (95%CI 0.5-0.7) and 0.6 (95%CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95%CI 3.9-4.9), 0.7 (95%CI 0.2-2.4), 0.0 (95%CI 0.0-0.1) and 0.0 (95%CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2 and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the risk of CVST, both with and without thrombocytopenia, was the highest in the 18-24 years age group (7.3 per million, 95%CI 2.8-18.8 and 3.7, 95%CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia was the lowest in ChAdOx1 nCov-19 recipients ≥70 years (0.2, 95%CI 0.0-1.3). Age Discussion: The risk of CVST with thrombocytopenia within 28 days of first dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S, comparing with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of mRNA vaccines for SARS-CoV-2.

Background and Purpose: Prolonged cardiac rhythm monitoring can reveal a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation (AF). We sought to evaluate the potential utility of available prolonged cardiac rhythm monitoring strategies with respect to secondary stroke prevention. Methods: We searched Medline and Scopus databases to identify randomized controlled clinical trials (RCTs) comparing AF detection, anticoagulation initiation and stroke recurrence rates in patients with history of recent IS or transient ischemic attack (TIA) receiving cardiac rhythm monitoring with implantable loop recorders (ILRs), 30-days external loop recorders or Holter monitors. We performed a network meta-analysis to combine direct and indirect evidence for any given pair of monitoring devices that were evaluated within a trial and reported effect estimates with risk ratios (RRs) and corresponding 95% confidence intervals (95%CIs). Results: We identified 5 RCTs including a total of 2202 patients (mean age 68 years, 40% women). In indirect analyses the likelihood of AF detection and anticoagulation initiation was higher for both ILR (RR=8.48, 95%CI: 3.41, 21.06; RR=3.29, 95%CI: 1.70-6.39) and external loop recorders (RR=3.06, 95%CI: 1.66, 5.61; RR=1.63, 95%CI: 1.03-2.58) compared to Holter devices. The probability of AF detection and anticoagulation initiation was lower for Holter and external loop recorders compared to ILR devices (RR=0.36, 95%CI: 0.15, 0.85 and RR=0.50, 95%CI: 0.25-0.98, respectively). No difference in the risk of stroke recurrence was found in the indirect comparisons of different cardiac rhythm monitoring strategies. Conclusion: The likelihood of AF detection and anticoagulation initiation after an ischemic stroke or TIA is higher with ILRs compared to both external loop recorders and Holter devices.

Background: The optimal timing for the initiation of anticoagulation in patients with acute ischemic stroke (AIS) related to atrial fibrillation (AF) remains uncertain. Observational studies assessing early anticoagulant initiation (≤14 days after index AIS) have provided conflicting results from the early use of non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs). Methods: We performed a meta-analysis of prospective observational studies and RCTs to assess the efficacy and safety of early anticoagulation in AF-related AIS. We also compared the efficacy and safety between NOAC and VKA regimens. A random-effects model was used to pool the individual risk ratios (RRs) and corresponding 95% confidence intervals (CIs) between the two groups. Recurrent ischemic stroke was defined as the primary outcome. Results: Nine eligible studies (7 observational, 2 RCTs) were identified, including 6,840 patients with AF-related AIS (pooled mean baseline NIHSS score: 5.5; 95%CI: 3.7-7.2) who received early anticoagulation. The overall ischemic stroke recurrence rate was 5% (95%CI: 3.3-7%) and differed (p=0.05) between studies reporting anticoagulation initiation within a week (2.5%, 95%CI: 0.2-7.4%) or two weeks (6.7%, 95%CI:4.6-9.1%) from index event. The corresponding proportions of patients experiencing a fatal outcome, symptomatic or asymptomatic ICH were 4% (95%CI: 1.6-7.5%), 1.2% (95%CI: 0.3-2.6%) and 13.2% (95%CI: 6.4-22.1%), respectively. Of the 2 identified RCTs, 136 and 135 patients were randomized to early anticoagulation with NOAC or VKA, respectively. Both groups had a similar risk for ischemic stroke recurrence (RR=0.78; 95%CI: 0.32, 1.91; p=0.59). No significant differences were uncovered between early NOAC or early VKA treatment initiation for the outcomes of mortality (RR=0.57; 95%CI: 0.11, 2.97; p=0.51), symptomatic ICH (RR=0.38; 95%CI: 0.02, 9.10; p=0.55) or asymptomatic ICH (RR=1.10; 95%CI: 0.73, 1.67; p=0.64). Conclusions: Preliminary evidence from RCTs on early anticoagulation after AF-related AIS suggest that NOACs have comparable efficacy to VKAs in preventing ischemic stroke recurrence. Large scale RCTs are warranted to evaluate the potential superiority of NOACs in terms of safety endpoints.

Background and Purpose: Tenecteplase is being evaluated as an alternative intravenous (IV) thrombolytic agent for the treatment of acute ischemic stroke (AIS) within ongoing randomized controlled clinical trials. However, several research teams have published their real-world experience with tenecteplase for the treatment of AIS. Methods: We searched Medline and Scopus for non-randomized clinical trials and observational cohort studies (prospective or retrospective) comparing IV tenecteplase (at any dose) to IV alteplase for patients with AIS. We calculated the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95%CI) for the association of tenecteplase vs. alteplase use and outcomes of interest. We pooled estimates using random-effects models. The primary outcome was the probability of modified Rankin scale (mRS) score of 0-2 at 90 days. Non-inferiority of tenecteplase vs. alteplase for the primary outcome in the meta-analysis was set at margins of 1.3% and 5% based on a recent survey. Results: We identified 6 studies comparing IV tenecteplase (n=583) to IV alteplase (n=904). Patients receiving tenecteplase had higher odds of successful recanalization (OR=2.82, 95%CI: 1.12, 7.11; adjusted OR=2.38, 95%CI: 1.18, 4.81) and early neurological improvement (OR=4.88, 95%CI: 2.03, 11.71; adjusted OR=7.60, 95%CI: 1.97, 29.41) when compared to alteplase. Tenecteplase was non-inferior (when applying the 5% non-inferiority margin) to alteplase for the primary outcome of mRS 0-2 at 90 days (absolute risk difference=0.06, 95%CI: -0.04, 0.15; OR=1.20, 95%CI: 0.86, 1.67; adjusted OR=1.24, 95%CI: 0.88, 1.76). No difference in the risk of symptomatic intracranial hemorrhage was uncovered between the two groups (OR=0.96, 95%CI: 0.45, 2.07; adjusted OR=0.92, 95%CI: 0.47, 1.81). Conclusion: Real world evidence suggests that tenecteplase has a comparable efficacy and safety profile to alteplase for the treatment of AIS, while being possibly superior in achieving successful reperfusion and early neurological improvement.

BackgroundEmergent carotid artery stenting (eCAS) is performed during mechanical thrombectomy for acute ischemic stroke due to tandem occlusion. However, the optimal management strategy in this setting is still unclear.ObjectiveTo carry out a systematic review and meta-analysis to investigate the safety and efficacy of eCAS in patients with tandem occlusion.MethodsSystematic review followed the PRISMA guidelines. Medline, EMBASE, and Scopus were searched from January 1, 2004 to March 7, 2022 for studies evaluating eCAS and no-stenting approach in patients with stroke with tandem occlusion. Primary endpoint was the 90-day modified Rankin Scale score 0–2; secondary outcomes were (1) symptomatic intracerebral hemorrhage (sICH), (2) recurrent stroke, (3) successful recanalization (Thrombolysis in Cerebral Infarction score 2b–3), (4) embolization in new territories, and (5) restenosis rate. Meta-analysis was performed using the Mantel-Haenszel method and random-effects modeling.ResultsForty-six studies reached synthesis. eCAS was associated with higher good functional outcome compared with the no-stenting approach (OR=1.52, 95% CI 1.19 to 1.95), despite a significantly increased risk of sICH (OR=1.97, 95% CI 1.23 to 3.15), and higher successful recanalization rate (OR=1.91, 95% CI 1.29 to 2.85). Restenosis rate was lower in the eCAS group than in the no-stenting group (2% vs 9%, p=0.001). Recanalization rate was higher in retrograde than antegrade eCAS (OR=0.51, 95% CI 0.28 to 0.93). Intraprocedural antiplatelets during eCAS were associated with higher rate of good functional outcome (60% vs 46%, p=0.016) and lower rate of sICH (7% vs 11%; p=0.08) compared with glycoprotein IIb/IIIa inhibitors.ConclusionsIn observational studies, eCAS seems to be associated with higher good functional outcome than no-stenting in patients with acute ischemic stroke due to tandem occlusion, despite the higher risk of sICH. Dedicated trials are needed to confirm these results.

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available. info:eu-repo/semantics/publishedVersion

© 2022 British Society for Haematology and John Wiley & Sons Ltd., The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I2 = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I2 = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I2 = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE.