Direct oral anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study.

Introduction: Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking. Methods: DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting. Discussion: DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT. Clinical trial registration: ClinicalTrials.gov, NCT04660747.

Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) associated with pregnancy and puerperium has long been recognized, with poor information in terms of functional outcomes. Our objective was to analyze risk factors, clinical, imaging, and laboratory variables to predict functional outcome and death in this population. METHODS: CVT registries from three referral centers from Pakistan, Turkey, and Mexico, recruiting prospective cases, were combined for CVT associated with pregnancy or puerperium. Datasets and variables were standardized. Demographic characteristics, presentation, risk factors, and functional outcomes in pregnancy/puerperium-related CVT were analyzed. Binary logistic regression was used to assess predictors of outcome. The main outcome was modified Rankin score >2 at 30 days and mortality at 30 days. RESULTS: Five hundred fifty-three cases (median age 28 years [IQR 23-34]) of CVT associated with pregnancy and puerperium were included; 439 cases (79.4%) happened in the puerperium and 20.6% during pregnancy (53.5% occurred during the first trimester). Anemia (36.7%) and dehydration (22.9%) were the commonest obstetric risk factors identified. Predictors of poor outcome (mRS >2) were encephalopathy (OR 12.8, p < 0.001), cases from Mexican origin (OR 3.1, p = 0.004), fever/puerperal infection (OR 2.7, p = 0.02), and anemia (OR 2.2, p = 0.01). Cases from Mexican origin (OR 12.0, p = 0.003) and Encephalopathy (OR 7.7, p < 0.001), presented with the highest mortality association in the final adjusted model. DISCUSSION/CONCLUSION: In CVT associated with pregnancy and puerperium, encephalopathy, fever/puerperal infection, and anemia are associated with bad functional outcomes, meanwhile encephalopathy and cases from Mexican origin with higher mortality in the acute (30-days) of CVT onset. Anemia and infection are potential reversible predictors of poor outcome that clinicians should be aware of in order to prevent poor outcomes in these patients.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main Outcomes and Measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic.

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 <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >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 (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.

COVID-19 Lockdown Effects on Acute Stroke Care in Latin America.

OBJECTIVES: COVID-19 pandemic has forced important changes in health care worldwide. Stroke care networks have been affected, especially during peak periods. We assessed the impact of the pandemic and lockdowns in stroke admissions and care in Latin America. MATERIALS AND METHODS: A multinational study (7 countries, 18 centers) of patients admitted during the pandemic outbreak (March-June 2020). Comparisons were made with the same period in 2019. Numbers of cases, stroke etiology and severity, acute care and hospitalization outcomes were assessed. RESULTS: Most countries reported mild decreases in stroke admissions compared to the same period of 2019 (1187 vs. 1166, p = 0.03). Among stroke subtypes, there was a reduction in ischemic strokes (IS) admissions (78.3% vs. 73.9%, p = 0.01) compared with 2019, especially in IS with NIHSS 0-5 (50.1% vs. 44.9%, p = 0.03). A substantial increase in the proportion of stroke admissions beyond 48 h from symptoms onset was observed (13.8% vs. 20.5%, p < 0.001). Nevertheless, no differences in total reperfusion treatment rates were observed, with similar door-to-needle, door-to-CT, and door-to-groin times in both periods. Other stroke outcomes, as all-type mortality during hospitalization (4.9% vs. 9.7%, p < 0.001), length of stay (IQR 1-5 days vs. 0-9 days, p < 0.001), and likelihood to be discharged home (91.6% vs. 83.0%, p < 0.001), were compromised during COVID-19 lockdown period. CONCLUSIONS: In this Latin America survey, there was a mild decrease in admissions of IS during the COVID-19 lockdown period, with a significant delay in time to consultations and worse hospitalization outcomes.

Risk factors for ischemic antiphospholipid syndrome: A case-control study.

OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.

Acute symptomatic seizures in cerebral venous thrombosis.

OBJECTIVE: To identify characteristics, predictors, and outcomes of acute symptomatic seizures (ASS) in cerebral venous thrombosis (CVT), we investigated 1,281 consecutive adult patients with CVT included from 12 hospitals within the International CVT Consortium. METHODS: We defined ASS as any seizure between symptom onset and 7 days after diagnosis of CVT. We stratified ASS into prediagnosis and solely postdiagnosis ASS. Status epilepticus (SE) was also analyzed separately. We analyzed predictors for ASS and the association between ASS and clinical outcome (modified Rankin Scale) with multivariable logistic regression. RESULTS: Of 1,281 eligible patients, 441 (34%) had ASS. Baseline predictors for ASS were intracerebral hemorrhage (ICH; adjusted odds ratio [aOR] 4.1, 95% confidence interval [CI] 3.0-5.5), cerebral edema/infarction without ICH (aOR 2.8, 95% CI 2.0-4.0), cortical vein thrombosis (aOR 2.1, 95% CI 1.5-2.9), superior sagittal sinus thrombosis (aOR 2.0, 95% CI 1.5-2.6), focal neurologic deficit (aOR 1.9, 95% CI 1.4-2.6), sulcal subarachnoid hemorrhage (aOR 1.6, 95% CI 1.1-2.5), and female-specific risk factors (aOR 1.5, 95% CI 1.1-2.1). Ninety-three (7%) patients had solely postdiagnosis ASS, best predicted by cortical vein thrombosis (positive/negative predictive value 22%/92%). Eighty (6%) patients had SE, independently predicted by ICH, focal neurologic deficits, and cerebral edema/infarction. Neither ASS nor SE was independently associated with outcome. CONCLUSION: ASS occurred in one-third of patients with CVT and was associated with brain parenchymal lesions and thrombosis of the superficial system. In the absence of prediagnosis ASS, no subgroup was identified with sufficient risk of postdiagnosis ASS to justify prophylactic antiepileptic drug treatment. We found no association between ASS and outcome.

Late seizures in cerebral venous thrombosis.

OBJECTIVE: To 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. METHODS: We included consecutive adult patients from an international consortium of 12 hospital-based CVT registries. We excluded patients with a history of epilepsy or with <8 days of follow-up. We defined LS as seizures occurring >7 days after diagnosis of CVT. We used multivariable Cox regression to identify predictors of LS. RESULTS: We 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. CONCLUSION: During 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.

Sex Differences Among Participants in the Latin American Stroke Registry.

Background Reports on sex differences in stroke outcome and risk factors are scarce in Latin America. Our objective was to analyze clinical and prognostic differences according to sex among participants in the LASE (Latin American Stroke Registry). Methods and Results Nineteen centers across Central and South America compiled data on demographics, vascular risk factors, clinical stroke description, ancillary tests, and functional outcomes at short-term follow-up of patients included from January 2012 to January 2017. For the present study, all these variables were analyzed according to sex at hospital discharge. We included 4788 patients with a median in-hospital stay of 8 days (interquartile range, 5-8); 2677 were male (median age, 66 years) and 2111 female (median age, 60 years). Ischemic stroke occurred in 4293: 3686 as cerebral infarction (77%) and 607 as transient ischemic attack cases (12.7%); 495 patients (10.3%) corresponded to intracerebral hemorrhage. Poor functional outcome (modified Rankin scale, 3-6) was present in 1662 (34.7%) patients and 38.2% of women (P<0.001). Mortality was present in 6.8% of the registry, with 7.8% in women compared with 6.0% in men (P=0.01). Death and poor functional outcome for all-type stroke showed a higher risk in female patients (hazard ratio, 1.3, P=0.03; and hazard ratio, 1.1, P=0.001, respectively). Conclusions A worse functional outcome and higher mortality rates occurred in women compared with men in the LASE, confirming sex differences issues at short-term follow-up.

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

OBJECTIVE: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence. METHODS: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration. RESULTS: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ2: 12.1 [p = 0.357] and χ2: 21.7 [p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively. CONCLUSIONS: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.

Priorities to reduce the burden of stroke in Latin American countries.

The large and increasing burden of stroke in Latin American countries, and the need to meet the UN and WHO requirements for reducing the burden from non-communicable disorders (including stroke), brought together stroke experts and representatives of the Ministries of Health of 13 Latin American countries for the 1st Latin American Stroke Ministerial meeting in Gramado, Brazil, to discuss the problem and identify ways of cooperating to reduce the burden of stroke in the region. Discussions were focused on the regional and country-specific activities associated with stroke prevention and treatment, including public stroke awareness, prevention strategies, delivery and organisation of care, clinical practice gaps, and unmet needs. The meeting culminated with the adoption of the special Gramado Declaration, signed by all Ministerial officials who attended the meeting. With agreed priorities for stroke prevention, treatment, and research, an opportunity now exists to translate this Declaration into an action plan to reduce the burden of stroke.

Diagnostic accuracy of noncontrast CT imaging markers in cerebral venous thrombosis.

OBJECTIVE: To assess the added diagnostic value of semiquantitative imaging markers on noncontrast CT scans in cerebral venous thrombosis (CVT). METHODS: In a retrospective, multicenter, blinded, case-control study of patients with recent onset (<2 weeks) CVT, 3 readers assessed (1) the accuracy of the visual impression of CVT based on a combination of direct and indirect signs, (2) the accuracy of attenuation values of the venous sinuses in Hounsfield units (with adjustment for hematocrit levels), and (3) the accuracy of attenuation ratios of affected vs unaffected sinuses in comparison with reference standard MRI or CT angiography. Controls were age-matched patients with (sub)acute neurologic presentations. RESULTS: We enrolled 285 patients with CVT and 303 controls from 10 international centers. Sensitivity of visual impression of thrombosis ranged from 41% to 73% and specificity ranged from 97% to 100%. Attenuation measurement had an area under the curve (AUC) of 0.78 (95% confidence interval [CI] 0.74-0.81). After adjustment for hematocrit, the AUC remained 0.78 (95% CI 0.74-0.81). The analysis of attenuation ratios of affected vs unaffected sinuses had AUC of 0.83 (95% CI 0.8-0.86). Adding this imaging marker significantly improved discrimination, but sensitivity when tolerating a false-positive rate of 20% was not higher than 76% (95% CI 0.70-0.81). CONCLUSION: Semiquantitative analysis of attenuation values for diagnosis of CVT increased sensitivity but still failed to identify 1 out of 4 CVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that visual analysis of plain CT with or without attenuation measurements has high specificity but only moderate sensitivity for CVT.

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

A Practical Score for Prediction of Outcome After Cerebral Venous Thrombosis.

Background: Most patients with cerebral venous thrombosis (CVT) have independent survival in the short term. However, identification of high-risk individuals with an unfavorable outcome is a challenging task. We aimed to develop a CVT grading scale (CVT-GS) to aid in the short-term clinical decision-making. Methods: We included 467 consecutive patients with CVT who were hospitalized from 1981 to 2015 in two third-level referral hospitals. Factors associated with 30-day mortality were selected with bivariate analyses to integrate a Cox proportional-hazards model to determine components of the final scoring. After the scale was configured, the prognostic performance was tested for prediction of short-term death or moderately impaired to death [modified Rankin scale (mRS) > 2]. CVT-GS was categorized as mild, moderate or severe for the prediction of 30-day fatality rate and a probability of mRS > 2. Results: The 30-day case fatality rate was 9.0%. The CVT-GS (0-13 points; more points predicting poorer outcomes) was composed of parenchymal lesion size > 6 cm (3 points), bilateral Babinski signs (3 points), male sex (2 points), parenchymal hemorrhage (2 points), and level of consciousness (coma: 3 points, stupor: 2, somnolence: 1, and alert: 0). CVT was categorized as mild (0-2 points, 0.4% fatality rate), moderate (3-7 points, 9.9% fatality rate), or severe (8-13 points, 61.4% fatality rate). The CVT-GS had an accuracy of 91.6% for the prediction of 30-day mortality and 85.3% for mRS > 2. Conclusions: CVT-GS is a practical clinical tool for prediction of outcome after CVT. This score may aid in clinical decision-making and could serve to stratify patients enrolled in clinical trials.