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Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (≥85y = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction = 0.129), adjusted (p interaction = 0.094) or weighted (p interaction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2021.

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (

BACKGROUND AND PURPOSE: We systematically evaluated the impact of the coronavirus 2019 (COVID-19) pandemic on stroke care across the world. METHODS: Observational studies comparing characteristics, acute treatment delivery, or hospitalization outcomes between patients with stroke admitted during the COVID-19 pandemic and those admitted before the pandemic were identified by Medline, Scopus, and Embase databases search. Random-effects meta-analyses were conducted for all outcomes. RESULTS: We identified 46 studies including 129 491 patients. Patients admitted with stroke during the COVID-19 pandemic were found to be younger (mean difference, -1.19 [95% CI, -2.05 to -0.32]; I2=70%) and more frequently male (odds ratio, 1.11 [95% CI, 1.01-1.22]; I2=54%) compared with patients admitted with stroke in the prepandemic era. Patients admitted with stroke during the COVID-19 pandemic, also, had higher baseline National Institutes of Health Stroke Scale scores (mean difference, 0.55 [95% CI, 0.12-0.98]; I2=90%), higher probability for large vessel occlusion presence (odds ratio, 1.63 [95% CI, 1.07-2.48]; I2=49%) and higher risk for in-hospital mortality (odds ratio, 1.26 [95% CI, 1.05-1.52]; I2=55%). Patients with acute ischemic stroke admitted during the COVID-19 pandemic had higher probability of receiving endovascular thrombectomy treatment (odds ratio, 1.24 [95% CI, 1.05-1.47]; I2=40%). No difference in the rates of intravenous thrombolysis administration or difference in time metrics regarding onset to treatment time for intravenous thrombolysis and onset to groin puncture time for endovascular thrombectomy were detected. CONCLUSIONS: The present systematic review and meta-analysis indicates an increased prevalence of younger patients, more severe strokes attributed to large vessel occlusion, and higher endovascular treatment rates during the COVID-19 pandemic. Patients admitted with stroke during the COVID-19 pandemic had higher in-hospital mortality. These findings need to be interpreted with caution in view of discrepant reports and heterogeneity being present across studies. © 2021 Lippincott Williams and Wilkins. All rights reserved.

Objective: Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations. Methods: We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9–1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8–1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1–0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43–8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62–9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00–1.94, I2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65–3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35–1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19–9.80, I2 = 45%). Interpretation: SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380–388. © 2020 American Neurological Association

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary. © The Author(s), 2021.

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either Vitamin K antagonists or nonVitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 The Authors.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT. © European Stroke Organisation 2020.

Background: Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether combining ischemic and hemorrhagic stroke risk in individual patients might provide a meaningful paradigm for risk stratification. Methods: We enrolled consecutive patients with anticoagulation-associated ICH in 15 tertiary centers in the USA, Europe and Asia between 2015 and 2017. Each patient was assigned baseline ischemic stroke and hemorrhage risk based on their CHA2DS2-VASc and HAS-BLED scores. We computed a net risk by subtracting hemorrhagic from ischemic risk. If the sum was positive the patient was assigned a “Favorable” indication for anticoagulation; if negative, “Unfavorable”. Results: We enrolled 357 patients [59% men, median age 76 (68–82) years]. 31% used non-vitamin K antagonist (NOAC). 191 (53.5%) patients had a favorable indication for anticoagulation prior to their ICH; 166 (46.5%) unfavorable. Those with unfavorable indication were younger [72 (66–80) vs 78 (73–84) years, p = 0.001], with lower CHA2DS2-VASc score [3(3–4) vs 5(4–6), p < 0.001]. Those with favorable indication had a significantly higher prevalence of most cardiovascular risk factors and were more likely to use a NOAC (35% vs 25%, p = 0.045). Both groups had similar prevalence of hypertension and chronic kidney disease. Conclusions: In this anticoagulation-associated ICH cohort, baseline hemorrhagic risk exceeded ischemic risk in approximately 50%, highlighting the importance of careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining 50% suffered an ICH despite excess baseline ischemic risk, stressing the need for biomarkers to allow more precise estimation of hemorrhagic complication risk. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Background and Purpose Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. Methods We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0–1 and 0–2 respectively. Results We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P

Zateyshchikov, Dmitry A/0000-0001-7065-2045; Vyshnyvetskyy, Ivan/0000-0001-7228-3052; Bustillo, Sonia Ruiz/0000-0002-6074-914X; Maslovskyi, Valentyn/0000-0001-5184-1799; Ruzic, Alen/0000-0001-5031-2975; Nikolaev, Konstantin/0000-0003-4601-6203; Musial, Jacek/0000-0002-8994-0036; Malynovsky, Yaroslav V/0000-0002-9118-1104; Tsivgoulis, Georgios/0000-0002-0640-3797; Maslovskyi, Valentyn/0000-0001-5184-1799; Grinshtein, Yury/0000-0001-8847-235X; Shpagina, Lyubov/0000-0003-0871-7551; Yildiz, Oznur/0000-0002-5379-6829; Marchev, Sotir/0000-0001-9250-510X; Weitz, Jeffrey/0000-0002-1092-7550; Apartsin, Konstantin A/0000-0003-0577-9001; Reis, Gilmar/0000-0002-4847-1034; Baker, Ross/0000-0002-2728-6788; Koziolkin, Olexandr/0000-0001-9878-5798; Barbarash, Olga/0000-0002-4642-3610; Sala-Llinas, Ernest/0000-0002-6499-1638; Gallus, Alexander/0000-0001-7347-9989; lodigiani, corrado/0000-0002-9152-9385; Kosmacheva, Elena/0000-0001-8600-0199; Ramacciotti, Eduardo/0000-0002-5735-1333; Khorana, Alok/0000-0002-9509-0998; Giorgi-Pierfranceschi, Matteo/0000-0002-7988-9652; Torbicki, Adam/0000-0003-3475-8832; Abragamovic, Orest/0000-0001-6862-6809; Jara-Palomares, Luis/0000-0002-4125-3376; Prozesky, Hans/0000-0001-9715-3449; Andreev, Denis/0000-0002-0276-7374; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463; Apostolovic, Svetlana/0000-0001-9015-297X; Gregorio, Tiago/0000-0002-0131-9430; Sanchez Martinez, Rosario/0000-0003-0408-3029; Antonicelli, Roberto/0000-0002-5921-1828; Konstantinides, Stavros/0000-0001-6359-7279; Karapanayiotides, Theodoros/0000-0002-2357-7967; Repin, Alexey/0000-0001-7123-0645 WOS: 000445020900006 PubMed: 30145946 BACKGROUND Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. METHODS In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma n-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. RESULTS Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). CONCLUSIONS Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. Janssen Research and Development; Daiichi SankyoDaiichi Sankyo Company Limited; Portola; Boehringer IngelheimBoehringer Ingelheim; JanssenJohnson & Johnson USAJanssen Biotech Inc; BayerBayer AG; BMS PfizerPfizer; Aspen; Sanofi; University of Cincinnati and Spectrum Health; PfizerPfizer; ATLAS Group (Colorado Prevention Center); Johnson JohnsonJohnson & Johnson USA; Ortho-McNeil-JanssenJohnson & Johnson USAJanssen Biotech Inc; Bayer/JanssenJohnson & Johnson USAJanssen Biotech IncBayer AG; MerckMerck & Company; AmgenAmgen Supported by Janssen Research and Development.r Dr. Spyropoulos reports receiving advisory board fees from Daiichi Sankyo and Portola, grant support, consulting fees, and advisory board fees from Boehringer Ingelheim and Janssen, consulting fees and advisory board fees from Bayer, and a stipend from ATLAS Group (Colorado Prevention Center); Dr. Ageno, receiving grant support and advisory board fees from Bayer and BMS Pfizer and advisory board fees from Portola, Daiichi Sankyo, Aspen, Boehringer Ingelheim, and Sanofi; Dr. Albers, receiving consulting fees from Bayer; Dr. Elliott, receiving fees for serving on a steering committee from Bayer and lecture fees from the University of Cincinnati and Spectrum Health; Dr. Halperin, receiving consulting fees from Boehringer Ingelheim, Daiichi Sankyo, Pfizer, ATLAS Group (Colorado Prevention Center), Johnson & Johnson, and Ortho-McNeil-Janssen; Dr. Hiatt, receiving grant support from Janssen and Bayer; Dr. Steg, receiving grant support and fees for serving on a steering committee from Bayer/Janssen, grant support and lecture fees from Merck, grant support, consulting fees, lecture fees, and fees for serving as cochair of the ODYSSEY outcomes trial and the SCORED trial from Sanofi, grant support and fees for serving as chair of the CLARIFY registry from Servier, consulting fees and fees for serving on the executive steering committee for the REDUCE IT trial from Amarin, consulting fees and lecture fees from Amgen, consulting fees, lecture fees, and fees for critical event committee work from Bristol-Myers Squibb, fees for serving on the executive steering committee of the REDUAL PCI trial from Boehringer Ingelheim, fees for critical event committee work from Pfizer, consulting fees and fees for serving on the executive steering committee for the PARADISE MI trial from Novartis, consulting fees from Regeneron and Lilly, and consulting fees and fees for serving as cochair of the THEMIS trial from AstraZeneca; Dr. Weitz, receiving consulting fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer and Portola; Dr. Suh and Dr. Barnathan, being employed by Janssen Research and Development and owning stock in Johnson & Johnson; Dr. Spiro, being employed by and owning shares in Bayer U.S.; and Dr. Raskob, receiving consulting fees from Bayer, BMS, Boehringer Ingelheim, Eli Lilly, Portola, and Novartis and consulting fees and honoraria from Daiichi Sankyo and Pfizer. No other potential conflict of interest relevant to this article was reported.

Background: Occult paroxysmal atrial fibrillation (PAF) is a common and potential treatable cause of cryptogenic stroke (CS). We sought to prospectively identify independent predictors of atrial fibrillation (AF) detection in patients with CS and sinus rhythm on baseline electrocardiogram (ECG), without prior AF history. We had hypothesized that cardiac arrhythmia detection during neurosonology examinations (Carotid Duplex (CDU) and Transcranial Doppler (TCD)) may be associated with higher likelihood of AF detection. Methods: Consecutive CS patients were prospectively evaluated over a six-year period. Demographics, clinical and imaging characteristics of cerebral ischemia were documented. The presence of arrhythmia during spectral waveform analysis of CDU/TCD was recorded. Left atrial enlargement was documented during echocardiography using standard definitions. The outcome event of interest included PAF detection on outpatient 24-h Holter ECG recordings. Statistical analyses were performed using univariate and multivariate logistic regression models. Results: A total of 373 patients with CS were evaluated (mean age 60 ± 11 years, 67% men, median NIHSS-score 4 points). The rate of PAF detection of any duration on Holter ECG recordings was 11% (95% CI 8%–14%). The following three variables were independently associated with the likelihood of AF detection on 24-h Holter-ECG recordings in both multivariate analyses adjusting for potential confounders: age (OR per 10-year increase: 1.68; 95% CI: 1.19–2.37; p = 0.003), moderate or severe left atrial enlargement (OR: 4.81; 95% CI: 1.77–13.03; p = 0.002) and arrhythmia detection during neurosonology evaluations (OR: 3.09; 95% CI: 1.47–6.48; p = 0.003). Conclusion: Our findings underline the potential utility of neurosonology in improving the detection rate of PAF in patients with CS. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

BACKGROUND AND PURPOSE: Evidence suggests that cardioembolism represents the underlying mechanism in the minority of embolic strokes of undetermined source (ESUS). In this population-based study, we sought to compare the clinical and imaging characteristics as well as outcomes in patients with ESUS and cardioembolic stroke (CE). METHODS: We included consecutive patients with first-ever ischemic stroke (IS) from the previously published population-based Evros-Stroke-Registry identified as ESUS or CE according to standardized criteria. Baseline characteristics, admission NIHSS scores, cerebral edema, hemorrhagic transformation, stroke recurrence, functional outcomes (determined by modified Rankin Scale [mRS] scores), and mortality rates were recorded during the 1-year follow-up period. RESULTS: We identified 21 ESUS (3.7% of IS) and 211 CE (37.1% of IS) cases. Patients with ESUS were younger (median age: 68 years [interquartile range [IQR]: 61-75] vs 80 years [IQR: 75-84]; P

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10–25) and 16.6 (95%CI: 10–24) per 100,000 person-years. Patients with ESUS were younger (p

Background and Purpose-Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods-We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results-Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P

Background: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence. © European Stroke Organisation 2018.

Background and Purpose-Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of frst-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. Methods-Adult patients with frst-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classifcation were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. Results-We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefned: 3.0%) with a total follow-up time of 119805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confdence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). Conclusions-This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for effcient stroke prevention and treatment strategies in Northeastern Greece. © 2018 American Heart Association, Inc.

Objective: Whether intracerebral hemorrhage (ICH) associated with non–vitamin K antagonist oral anticoagulants (NOAC-ICH) has a better outcome compared to ICH associated with vitamin K antagonists (VKA-ICH) is uncertain. Methods: We performed a systematic review and individual patient data meta-analysis of cohort studies comparing clinical and radiological outcomes between NOAC-ICH and VKA-ICH patients. The primary outcome measure was 30-day all-cause mortality. All outcomes were assessed in multivariate regression analyses adjusted for age, sex, ICH location, and intraventricular hemorrhage extension. Results: We included 7 eligible studies comprising 219 NOAC-ICH and 831 VKA-ICH patients (mean age = 77 years, 52.5% females). The 30-day mortality was similar between NOAC-ICH and VKA-ICH (24.3% vs 26.5%; hazard ratio = 0.94, 95% confidence interval [CI] = 0.67–1.31). However, in multivariate analyses adjusting for potential confounders, NOAC-ICH was associated with lower admission National Institutes of Health Stroke Scale (NIHSS) score (linear regression coefficient = −2.83, 95% CI = −5.28 to −0.38), lower likelihood of severe stroke (NIHSS > 10 points) on admission (odds ratio [OR] = 0.50, 95% CI = 0.30–0.84), and smaller baseline hematoma volume (linear regression coefficient = −0.24, 95% CI = −0.47 to −0.16). The two groups did not differ in the likelihood of baseline hematoma volume < 30cm3 (OR = 1.14, 95% CI = 0.81–1.62), hematoma expansion (OR = 0.97, 95% CI = 0.63–1.48), in-hospital mortality (OR = 0.73, 95% CI = 0.49–1.11), functional status at discharge (common OR = 0.78, 95% CI = 0.57–1.07), or functional status at 3 months (common OR = 1.03, 95% CI = 0.75–1.43). Interpretation: Although functional outcome at discharge, 1 month, or 3 months was comparable after NOAC-ICH and VKA-ICH, patients with NOAC-ICH had smaller baseline hematoma volumes and less severe acute stroke syndromes. Ann Neurol 2018;84:702–712. © 2018 American Neurological Association

Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever stroke (FES). Adult patients with FES were registered during a 24-month period (2010–2012) and followed-up for 12 months. We calculated cumulative incidences of stroke mortality and recurrence. Univariable and multivariable Cox proportional hazards regression analyses were used to identify independent determinants of 1-year mortality and 1-year stroke recurrence. We prospectively documented 703 first ever stroke cases (mean age 75 ± 12 years; 52.8% males; ischemic stroke 80.8%, intracerebral hemorrhage 11.8%, subarachnoid hemorrhage 4.4%, undefined 3.0%) with a total follow-up time of 119,805 person-years. The cumulative incidence rates of mortality of all FES patients at 28 days, 3 months and 1 year were 21.3% (95% CI 18.5–24.5%), 26% (95% CI 22.9–29.4%) and 34.7% (95% CI 31.3–38.3%), respectively. The risk of 1-year mortality was independently (p < 0.05) associated with advancing age, history of hypertension, increased stroke severity on admission, and hemorrhagic FES type. Cumulative 1-year stroke mortality differed according to both index FES type (ischemic vs. hemorrhage; p < 0.001), but also across different ischemic stroke subtypes (p = 0.025). The cumulative incidence rates of recurrent stroke at 28 days, 3 months and 1 year were 2.0% (95% CI 1.2–3.6%), 4.2% (2.8–6.2%) and 6.7% (5.1–8.8%), respectively. Comparable to other population-based surveys, our study reports 1-year mortality and stroke recurrence rates in patients with FES. These findings highlight the need for effective secondary prevention strategies in a border region of southeastern Europe, which exhibits very high FES incidence rates. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.

The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D–T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor). © 2017, Springer Science+Business Media New York.

Background and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

Objective: To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF). Methods: We evaluated consecutive patients with NVAF with nontraumatic, anticoagulantrelated ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA-or DOAC-related ICH. Results: We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.66 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSSadm] score 13 points, interquartile range 6-21). DOAC-related (n 5 47) and VKA-related (n 5 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA2DS2-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSSadm scores (8 [3-14] vs 15 [7-25] points, p 5 0.003), median baseline hematoma volume (12.8 [4-40] vs 24.3 [11-58.8] cm3, p 5 0.007), and median ICH score (1 [0-2] vs 2 [1-3] points, p5 0.049). Severe ICH (.2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%, p 5 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (p 5 0.006), lower NIHSSadm scores (p 5 0.022), and lower likelihood of severe ICH (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13-0.87, p 5 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference 5 20.57, 95% CI 21.02 to 20.12, p 5 0.010) and lower in-hospital mortality rates (OR 5 0.44, 95% CI 0.21-0.91, p 5 0.030). Conclusions: DOAC-related ICH is associatedwith smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH. © 2017 American Academy of Neurology.

Objective - Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. Approach and Results - We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09-0.92; P=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07-10.0; P=0.037). Conclusions - We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association. © 2017 American Heart Association, Inc.

Background--The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within90 days)and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results--Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score > 4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions--In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days. © 2017 The Authors.

Background and Purpose The aim of this study was to investigate for a possible association between both prestroke CHA2DS2-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS ≥10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods: Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p < 0.001) and younger (p < 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p < 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p < 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes. © 2016, © European Stroke Organisation 2016.

Objectives: The cumulative safety and efficacy measures of percutaneous transluminal angioplasty and stenting (PTAS) for secondary stroke prevention in patients with symptomatic intracranial arterial stenosis (sICAS) have not previously been evaluated using a meta-analytical approach. Methods: We conducted a systematic review and random effects meta-analysis of all available randomized controlled trials (RCTs) evaluating the safety and efficacy of PTAS (in comparison with medical therapy) for sICAS. Results: Three RCTs (678 total patients) were included in the quantitative analysis. PTAS was associated with a higher risk of recurrent ischemic stroke in the territory of qualifying artery both within 30 days [risk ratio (RR) = 2.21, 95% confidence interval (CI) 1.10-4.43] and 1 year (RR = 1.92, 95% CI 1.10-3.36). PTAS was also related to a higher risk of any ischemic stroke within 30 days from the index event (RR = 2.08, 95% CI 1.17-3.71). The risk for intracranial hemorrhage was found to be higher in PTAS patients both within 30 days (RR = 10.60, 95% CI 1.98-56.62) and 1 year (RR = 8.15, 95% CI 1.50-44.34). The composite outcome of any stroke or death within 1 year (RR = 2.29, 95% CI 1.13-4.66) and 2 years (RR = 1.52, 95% CI 1.04-2.21) was higher in PTAS than in medical therapy. PTAS was associated with a higher risk of any stroke or death within 2 years in the sICAS subgroup located in posterior circulation (RR = 2.37, 95% CI 1.27-4.42). Conclusions: PTAS is associated with adverse early and long-term outcomes and should not be recommended in patients with sICAS. Further research to identify subgroups of patients who could also serve as candidates for future interventional trials along with efforts to reduce procedure-related complications are needed. © The Author(s), 2016.

Objective: Even though statin pretreatment is associated with better functional outcomes and lower risk of mortality in acute ischemic stroke, there are limited data evaluating this association in acute ischemic stroke due to large artery atherosclerosis (LAA), which carries the highest risk of early stroke recurrence. Methods: Consecutive patients with acute LAA were prospectively evaluated from 7 tertiary-care stroke centers during a 3-year period. Statin pretreatment, demographics, vascular risk factors, and admission and discharge stroke severity were recorded. The outcome events of interest were neurologic improvement during hospitalization (quantified as the relative decrease in NIH Stroke Scale score at discharge in comparison to hospital admission), favorable functional outcome (FFO) (defined as modified Rankin Scale score of 0-1), recurrent stroke, and death at 1 month. Statistical analyses were performed using univariable and multivariable Cox regression models adjusting for potential confounders. All analyses were repeated following propensity score matching. Results: Statin pretreatment was documented in 192 (37.2%) of 516 consecutive patients with LAA (mean age: 65 ± 13 years; 60.8% men; median NIH Stroke Scale score: 9 points, interquartile range: 5-18). Statin pretreatment was associated with greater neurologic improvement during hospitalization and higher rates of 30-day FFO in unmatched and matched (odds ratio for FFO: 2.44; 95% confidence interval [CI]: 1.07-5.53) analyses. It was also related to lower risk of 1-month mortality and stroke recurrence in unmatched and matched analyses (hazard ratio for recurrent stroke: 0.11, 95% CI: 0.02-0.46; hazard ratio for death: 0.24, 95% CI: 0.08-0.75). Conclusion: Statin pretreatment in patients with acute LAA appears to be associated with better early outcomes regarding neurologic improvement, disability, survival, and stroke recurrence. © 2016 American Academy of Neurology.

Anticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). The identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90 days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7 days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3 ± 9.5 years) underwent a TTE evaluation; 63 patients (7.4 %) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3 %) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2 %) among whom 51 (9.3 %) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7 %. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95 % CI 1.06–4.29, p = 0.033) and CHA2DS2-VASc score (OR 1.22; 95 % CI 1.04–1.45, p = 0.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon. © 2015, Springer-Verlag Berlin Heidelberg.

Background and Purpose - The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods - The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results - Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions - Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

The safety and efficacy of intravenous thrombolysis (IVT) in dissection-related ischemic stroke (DRIS) has not been established. We sought to determine safety and recovery rates of IVT in DRIS using prospective, international, multicenter data and by conducting a comprehensive meta-analysis of reported case series. We analyzed consecutive DRIS patients treated with IVT according to national guidelines during a 5-year period at six tertiary-care stroke centers, and also conducted a comprehensive review and meta-analysis of all available case series reporting safety outcomes in DRIS treated with IVT according to PRISMA guidelines. A total of 39 DRIS patients (mean age 60 ± 18 years; 59 % men; median NIHSS 13 points, IQR 9–17) received IVT in our multicenter study. Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, complete recanalization, favorable functional outcome (FFO; mRS-score of 0–1) and functional independence (FI; mRS-score of 0–2) were 0 % (adjusted Wald 95 % CI 0–8 %), 10 % (3–24 %), 55 % (40–70 %), 61 % (45–74 %) and 68 % (52–81 %). The pooled sICH and mortality rates in meta-analysis including 10 case series (234 IVT-DRIS patients) were 2 % (0–5 %) and 4 % (0–8 %). The pooled recanalization, FFO and FI rates were 45 % (26–67 %), 41 % (29–54 %) and 61 % (48–72 %), respectively. Substantial heterogeneity was only found for FFO (I2 = 61 %; p = 0.006). Subsequent meta-regression analysis identified baseline NIHSS and dissection in the posterior circulation as independent predictors of FFO (p

Background: There are growing concerns for the side effects of dabigatran etexilate (dabigatran), including higher incidence of dyspepsia and gastrointestinal bleeding. We conducted a multicenter early implementation study to prospectively evaluate the safety, efficacy and adherence to dabigatran for secondary stroke prevention. Methods: Consecutive atrial fibrillation (AF) patients with ischemic stroke (IS) or transient ischemic attack (TIA) received dabigatran for secondary stroke prevention during their hospital stay according to American Heart Association recommendations at five tertiary care stroke centers. The study population was prospectively followed and outcomes were documented. The primary and secondary safety outcomes were major hemorrhage and all other bleeding events respectively defined according to RE-LY trial methodology. Results: A total of 78 AF patients (mean age 71 ± 9years; 54% men; 81% IS, 19% TIA; median CHADS2 (Congestive heart failure, Hypertension, diabetes mellitus, age >75 years, prior stroke or TIA); range 2-5) score 4 were treated with dabigatran [(110mg bid (74%); 150mg bid (26%)]. During a mean follow-up period of 7 ± 5 months (range 1-18) we documented no cases of IS, TIA, intracranial hemorrhage, systemic embolism or myocardial infarction in AF patients treated with dabigatran. There were two (2.6%) major bleeding events (lower gastrointestinal bleeding) and two (2.6%) minor bleedings [hematuria (n = 1) and rectal bleeding (n = 1)]. Dabigatran was discontinued in 26% of the study population with high cost being the most common reason for discontinuation (50%). Discussion: Our pilot data indicate that dabigatran appears to be safe for secondary stroke prevention during the first year of implementation of this therapy. However, high cost may limit the long-term treatment of AF patients with dabigatran, leading to early discontinuation. © 2014, SAGE Publications. All rights reserved.

BACKGROUND: There are limited data available regarding symptomatic intracranial atherosclerosis (SIA) prevalence in Caucasians. We sought to investigate SIA prevalence among Caucasian patients hospitalized with acute cerebral ischemia (ACI) in a prospective, multicenter Transcranial Doppler sonography (TCD) study. METHODS: Consecutive patients with ACI were prospectively evaluated with TCD over a 24-month-period. The previously validated criteria of SONIA trial were used for detection of >50% intracranial stenosis with TCD. Brain angiography was performed to confirm the diagnosis in cases with abnormal TCD findings. SIA was diagnosed when there was evidence of a cerebral infarction in the territory of the stenotic artery (identified by TCD and confirmed by Magnetic resonance angiography [MRA]/Computed tomography angiography [CTA]). RESULTS: A total of 467 consecutive patients with ACI (60.4% men, mean age 58 ± 14 years) were evaluated. SIA was documented in 43 patients (9.2%; 95%CI: 6.9%-12.2%). The most common SIA location was M1MCA (34.9%) followed by TICA (18.8%). Diabetes mellitus (OR: 4.25, 95%CI: 2.18-8.26; P < .001) and hypertension (OR: 2.41, 95%CI: 1.02-5.67; P = .045) were independently associated with SIA on multivariate models adjusting for potential confounders. CONCLUSIONS: SIA was identified in almost 10% of patients admitted with symptoms of ACI. These preliminary findings support further collaborative initiatives among stroke physicians to increase the yield of SIA detection in Caucasian patients with ACI. © 2012 by the American Society of Neuroimaging.

We present an uncommon case of a 38-year-old man presented with bilateral subacute weakness of intrinsic hand muscles, manifesting as bilateral claw-hand, without sensory deficits and absent tendon reflexes in upper arms. Nerve conduction studies showed findings consistent with demyelinating GBS. During the fourth day of hospitalization the patient presented symmetrical distal leg weakness and was treated with intravenous immunoglobulin. © 2013 Elsevier B.V.

Background and purpose: A recent retrospective study using an online list service established by the American Academy of Neurology has suggested that ischaemic cerebrovascular events may occur in patients who undergo 'bubble studies' (BS) with either transcranial Doppler (TCD) or transoesophageal echocardiography (TOE). The safety of TCD-BS for right to left shunt (RLS) identification was evaluated prospectively in an international multicentre study. Methods: Consecutive patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attack (TIA)) were screened for potential ischaemic cerebrovascular events following injection of microbubbles during TCD-BS for identification of RLS at three tertiary care stroke centres. TCD-BS was performed according to the standardised International Consensus Protocol. TOE-BS was performed in selected cases for confirmation of TCD-BS. Results: 508 patients hospitalised with acute cerebral ischaemia (mean age 46±12 years, 59% men; 63% ischaemic stroke, 37% TIA) were investigated with TCDBS within 1 week of ictus. RLS was identified in 151 cases (30%). TOE-BS was performed in 101 out of 151 patients with RLS identified on TCD-BS (67%). It was positive in 99 patients (98%). The rate of ischaemic cerebrovascular complications during or after TCD-BS was 0% (95% CI by the adjusted Wald method: 0-0.6%). Structural cardiac abnormalities were identified in 38 patients, including atrial septal aneurysm (n=23), tetralogy of Fallot (n=1), intracardiac thrombus (n=2), ventricular septal defect (n=3) and atrial myxoma (n=1). Conclusion: TCD-BS is a safe screening test for identification of RLS, independent of the presence of cardiac structural abnormalities.

Objectives: A chronic state of impaired cerebral and cervical venous drainage, termed chronic cerebrospinal venous insufficiency (CCSVI), has recently been implicated in the pathogenesis of multiple sclerosis (MS). We performed a color-coded Doppler sonography case-control study to externally validate the CCSVI criteria. Methods: We prospectively evaluated consecutive patients with clinically definite MS and healthy volunteers using extracranial and transcranial color-coded Doppler sonography. The recently developed neurosonology criteria for CCSVI detection were used for interpretation of ultrasound assessments. The presence of venous reflux in cervical veins was assessed both in the sitting and upright position during a short period of apnea and after Valsalva maneuver. Results: We recruited 42 patients with MS (mean age 39 +/- 11 years, 17 men) and 43 control individuals (mean age 38 +/- 12 years, 16 men). Very good/excellent intrarater and interrater agreement (kappa values 0.82-1.00) was documented in 3 out of 5 CCSVI criteria. There was no evidence of stenosis or nondetectable Doppler flow in cervical veins in patients and controls. Reflux in internal jugular vein (IJV) was documented in 1 patient (2%) and 1 control subject (2%), both in sitting and supine posture during apnea. After performing Valsalva maneuver, we documented the presence of IJV valve incompetence in 3 patients with MS (7%) and 4 healthy volunteers (9%; p > 0.999). Conclusions: With established reproducibility of venous ultrasound testing, our data argue against CCSVI as the underlying mechanism of MS. Without further independent validation of CCSVI, potentially dangerous endovascular procedures, proposed as novel therapy for MS, should not be performed outside controlled clinical trials. Neurology (R) 2011; 77: 1241-1245

The diagnosis of peripheral diabetic neuropathy is based on clinical examination. Nerve conduction study (NCS) enables earlier diagnosis, but it is demanding and requires specialised personnel. In an attempt to simplify the procedure, this study aimed to identify a new electrophysiological index, which might correlate with results obtained on standardised NCS in patients with long-standing type 2 diabetes.Medical records of type 2 diabetic patients evaluated for neuropathy by NCS were reviewed retrospectively. This analysis included 104 patients (50 men, 54 women) with a mean age of 67.1±5.5 years and mean diabetes duration of 13.1±2.7 years. NCS was performed on radial, ulnar, sural, and peroneal nerves. Neuropathy was defined as impaired NCS. Ratios of neurophysiological parameters from these nerves were calculated and each of them was compared with diagnosis of neuropathy.The sural sensory/radial motor amplitude ratio had the best combination of sensitivity (85%) and specificity (71%) for neuropathy. It also remained the strongest independent predictor of neuropathy in multivariate regression analysis: low levels of this ratio yielded an odds ratio of 7.7 for neuropathy.The sural sensory/radial motor amplitude ratio has a high sensitivity and a moderately high specificity for the diagnosis of neuropathy, low levels being associated with a nearly eightfold increase in the risk for neuropathy. These results encourage further evaluation of this and other electrophysiological indices to enable wider availability of NCS.