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BackgroundPrior studies indicated a decrease in the incidences of aneurysmal subarachnoid haemorrhage (aSAH) during the early stages of the COVID-19 pandemic. We evaluated differences in the incidence, severity of aSAH presentation, and ruptured aneurysm treatment modality during the first year of the COVID-19 pandemic compared with the preceding year.MethodsWe conducted a cross-sectional study including 49 countries and 187 centres. We recorded volumes for COVID-19 hospitalisations, aSAH hospitalisations, Hunt-Hess grade, coiling, clipping and aSAH in-hospital mortality. Diagnoses were identified by International Classification of Diseases, 10th Revision, codes or stroke databases from January 2019 to May 2021.ResultsOver the study period, there were 16 247 aSAH admissions, 344 491 COVID-19 admissions, 8300 ruptured aneurysm coiling and 4240 ruptured aneurysm clipping procedures. Declines were observed in aSAH admissions (−6.4% (95% CI −7.0% to −5.8%), p=0.0001) during the first year of the pandemic compared with the prior year, most pronounced in high-volume SAH and high-volume COVID-19 hospitals. There was a trend towards a decline in mild and moderate presentations of subarachnoid haemorrhage (SAH) (mild: −5% (95% CI −5.9% to –4.3%), p=0.06; moderate: −8.3% (95% CI −10.2% to –6.7%), p=0.06) but no difference in higher SAH severity. The ruptured aneurysm clipping rate remained unchanged (30.7% vs 31.2%, p=0.58), whereas ruptured aneurysm coiling increased (53.97% vs 56.5%, p=0.009). There was no difference in aSAH in-hospital mortality rate (19.1% vs 20.1%, p=0.12).ConclusionDuring the first year of the pandemic, there was a decrease in aSAH admissions volume, driven by a decrease in mild to moderate presentation of aSAH. There was an increase in the ruptured aneurysm coiling rate but neither change in the ruptured aneurysm clipping rate nor change in aSAH in-hospital mortality.Trial registration numberNCT04934020.

Background: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. Methods: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. Results: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). Conclusions: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered. © 2021 European Academy of Neurology

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: An alarming cerebro/cardiovascular collateral damage, reflected by a decline in admissions for acute stroke (AS) and acute coronary syndrome (ACS), was observed during the initial phase of the COVID-19 pandemic, thereby leading to a re-design of public campaigns. However, there are limited data regarding the AS and ACS hospitalization rates during the second wave of the pandemic, which was followed by re-imposition of lockdowns. Methods: We calculated the rate of AS and ACS hospitalizations from three representative tertiary care hospitals in Greece during a 2-month period (November–December 2020) of the second wave of the COVID-19 pandemic compared with the corresponding control period in 2019 from three representative tertiary care hospitals in Greece. This was a follow-up study with identical design to our previous report evaluating AS and ACS hospitalizations during the first wave of the pandemic (March–April 2020). Results: Compared with 2019, there was a 34% relative reduction of AS hospitalizations [incidence rate ratio (IRR): 0.66, 95% confidence interval (CI): 0.48–0.92, p = 0.013] and 33% relative reduction of ACS hospitalizations (IRR: 0.67, 95% CI: 0.54–0.83, p < 0.001) during the second wave of the COVID-19 pandemic. The relative reduction was smaller and did not reach the level of statistical significance for the respective syndromes (haemorrhagic stroke: IRR 0.87, 95% CI: 0.41–1.82, p = 0.71; ST-elevation myocardial infarction: IRR 0.81, 95% CI: 0.57–1.14, p = 0.22). Conclusion: AS and ACS hospitalizations were persistently reduced during the second wave of the COVID-19 pandemic compared with 2019 in Greece. This decline was similar to the observations during the first wave despite the large differences in the epidemiological COVID-19 burden. Lockdowns, a common characteristic in both waves, appear to have a detrimental indirect impact on cerebro/cardiovascular diseases in the general population. © The Author(s), 2021.

Background and purpose: A remarkable decline in admissions for acute stroke and acute coronary syndrome (ACS) has been reported in countries severely hit by the COVID-19 pandemic. However, limited data are available from countries with less COVID-19 burden focusing on concurrent stroke and ACS hospitalisation rates from the same population. Methods: The study was conducted in three geographically and demographically representative COVID-19 referral university hospitals in Greece. We recorded the rate of stroke and ACS hospital admissions during a 6-week period of the COVID-19 outbreak in 2020 and compared them with the rates of the corresponding period in 2019. Results: We found a greater relative reduction of stroke admissions (51% [35 vs. 71]; incidence rate ratio [IRR]: 0.49, p = 0.001) compared with ACS admissions (27% [123 vs. 168]; IRR: 0.73, p = 0.009) during the COVID-19 outbreak (p = 0.097). Fewer older (>65 years) patients (stroke: 34.3% vs. 45.1%, odds ratio [OR]: 0.64, p = 0.291; ACS: 39.8% vs. 54.2%, OR: 0.56, p = 0.016) were admitted during the COVID-19 compared with the control period. Conclusions: Hospitalisation rates both for stroke and ACS were reduced during the COVID-19 outbreak in a country with strict social distancing measures, low COVID-19 incidence and low population mortality. Lack of triggers for stroke and ACS during social distancing/quarantining may explain these observations. However, medical care avoidance attitudes among cerebro/cardiovascular patients should be dissipated amidst the rising second COVID-19 wave. © 2020 European Academy of Neurology

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities. © The Author(s), 2021.

Giant cell arteritis (GCA) is a systemic inflammatory arteriopathy of medium and large-sized arteries, predominantly affecting branches of the external carotid artery. Ischemic stroke has been reported in 2.8–7% of patients diagnosed with GCA. The majority of ischemic strokes may involve the posterior circulation as a result of vertebral and/or, less frequently, of basilar artery vasculitis. Prompt diagnosis is crucial since high-dose corticosteroid treatment is highly effective in preventing the occurrence or recurrence of ischemic complications, including posterior circulation ischemic stroke in cases with vertebrobasilar involvement. Cervical duplex sonography (CDS) of the temporal arteries is a powerful diagnostic tool with high sensitivity and specificity for the diagnosis of GCA. In cases with clinical suspicion or a temporal artery ultrasonographic confirmation of GCA, a detailed evaluation of the cervical, axillary, and intracranial arteries with CDS and transcranial-duplex-sonography, respectively, should be part of the ultrasound examination protocol. Specifically, signs of extracranial vertebral artery wall inflammation (“halo” sign) and focal luminar stenoses may be accurately depicted by ultrasounds in high-risk patients or individuals with ischemic stroke attributed to GCA. In this review, we present three cases of GCA and posterior circulation ischemic complications that were initially evaluated with comprehensive neurosonology protocol and were promptly diagnosed with GCA based on the characteristic “halo” sign in the temporal and vertebral arteries. In addition, we discuss the relevant literature concerning the utility of CDS for the early diagnosis of GCA, focusing on the subtype with extracranial arterial involvement, particularly that of the vertebral arteries. © 2021 American Society of Neuroimaging

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.

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.

IgG antibodies to myelin oligodendrocyte glycoprotein (MOG) detected by cell based assays (CBA) have been identified in a constantly expanding spectrum of CNS demyelinating disorders. However, a universally accepted CBA has not been adopted yet. We aimed to analyze the clinical and radiological features of patients with anti-MOG IgG1-antibodies detected with a live-cell CBA and to compare the three most popular MOG-CBAs. We screened sera from 1300 Greek patients (including 426 patients referred by our 8 clinics) suspected for anti-MOG syndrome, and 120 controls with the live-cell MOG-CBA for IgG1-antibodies. 41 patients, versus 0 controls were seropositive. Clinical, serological and radiological data were available and analyzed for the 21 seropositive patients out of the 426 patients of our clinics. Their phenotypes were: 8 optic neuritis, 3 myelitis, 3 neuromyelitis optica, 2 encephalomyelitis, 2 autoimmune encephalitis and 3 atypical MS. We then retested all sera of our 426 patients with the other two most popular MOG-CBAs for total IgG (a live-cell and a commercial fixed-cell CBAs). Seven IgG1-seropositive patients were seronegative for one or both IgG-CBAs. Yet, all 21 patients had clinical and radiological findings previously described in MOG-antibody associated demyelination disease supporting the high specificity of the IgG1-CBA. In addition, all IgG1-CBA-negative sera were also negative by the IgG-CBAs. Also, all controls were negative by all three assays, except one serum found positive by the live IgG-CBA. Overall, our findings support the wide spectrum of anti-MOG associated demyelinating disorders and the superiority of the MOG-IgG1 CBA over other MOG-CBAs. © 2020 Elsevier B.V.

Introduction: Percutaneous closure of patent foramen ovale (PFO) in selected patients with cryptogenic cerebrovascular ischemic events (CEs) decreases the risk of recurrent stroke; however, optimal patient selection criteria are still under investigation. Candidates for PFO closure are usually selected from the pool of CE patients with a high risk of Paradoxical Embolism (RoPE) score. The RoPE score calculates the probability that PFO is causally related to stroke, based on PFO prevalence in patients with CE compared with that in healthy subjects. The latter has been set at 25% based on the average of autopsy and transesophageal echocardiography (TEE) studies. Methods: We conducted a comprehensive review of studies investigating PFO prevalence in general population and in patients with CE and non-CE using autopsy, TEE, transcranial Doppler (TCD) or transthoracic echocardiography (TTE). Studies were excluded if they (1) reported data from referred subjects with underlying cerebrovascular disease or (2) did not specify etiologically the events. Results: In healthy/control subjects, PFO prevalence was 24.2% (1,872/7,747) in autopsy studies, 23.7% (325/1,369) in TEE, 31.3% (111/355) in TCD, and 14.7% (186/1,267) in TTE studies. All diagnostic modalities included PFO prevalence was higher in CE compared with healthy/control population [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.5–3.8] and compared with non-CE (OR = 2.3, 95% CI = 2.0–2.6). In patients with CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (48.9 vs. 27.3%, p < 0.0001, OR = 2.6 with 95% CI = 2.0–3.3) or TCD (58.1 vs. 41%, OR = 1.9, 95% CI = 1.6–2.5), but not TTE (53.3 vs. 37.5%, p = 0.16). Regarding non-CE, PFO prevalence in the young compared to the old was higher when the diagnostic modality was TEE (20 vs. 12.9%, OR = 1.7, 95% CI = 1.0–2.8) but not TTE (10.4 vs. 7.8%, p = 0.75) or TCD (22.8 vs. 20.1%, p = 0.56). Conclusions: Given the limitations of autopsy and TEE studies, there is good reason not to take a fixed 25% PFO prevalence for granted. The estimation of degree of causality may be underestimated or overestimated in populations with PFO prevalence significantly lower or higher than the established. Given the high sensitivity, non-invasive nature, low cost, and repeatability of TCD, future large-scale TCD-based studies should investigate potential heterogeneity in PFO prevalence in different healthy racial/ethnic populations. © Copyright © 2020 Koutroulou, Tsivgoulis, Tsalikakis, Karacostas, Grigoriadis and Karapanayiotides.

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.

Background: The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely. Methods: Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11–20), and small (⩽10). Results: PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS (p = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124); p = 0.1] and to nonCS [7.1% (4/56), p = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9–10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was

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.

Although intracerebral hemorrhage (ICH) score is used to provide an estimate on the probability of mortality following spontaneous ICH of any cause, its utility has not been exclusively tested in ICH patients with history of treatment with vitamin K antagonists (VKAs) or non-vitamin K oral anticoagulants (NOACs). The aim of the present report is to investigate the utility of ICH score for mortality prognostication of VKA-ICH and NOAC-ICH patients. We used receiver operating characteristic curve analyses to estimate the accuracy parameters for the different values of ICH score in the prognosis of mortality within 30-days after the onset of NOAC-ICH or VKA-ICH. We analyzed data from 108 NOAC-ICH and 241 VKA-ICH patients (median age 76 years, 58% males, median NIHSS score 11 points, median ICH-score 2 points). ICH score of 4 points was uncovered to be the most favorable threshold for the prediction of 30-day mortality both after NOAC-ICH (sensitivity: 57.7%, specificity: 98.8%) or VKA-ICH (sensitivity: 42.1%, specificity: 92.6%). However, comparison of the areas under the curve (AUC) suggested a cumulatively higher (p = .001) predictive value of ICH-score in the prognostication of 30-day mortality after ICH related to the use of NOACs (AUC: 0.92, 95%CI: 0.86–0.98) compared to the ICH related to the use of VKAs (AUC: 0.77, 95%CI: 0.70–0.83). In conclusion, ICH score seems to have an adequate predictive utility in the prognostication of 30-day mortality following an ICH related to the use of oral anticoagulants, with better yield in ICH cases associated with the use of NOACs. © 2019 Elsevier B.V.

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: Vascular aspects like global cerebral hypoperfusion are frequently reported in patients with multiple sclerosis (MS). Although mechanistic question remains unanswered, this hemodynamic impairment may be caused by a widespread endothelial dysfunction. Furthermore, impaired cerebrovascular reactivity (CVR) has been described in patients with MS by means of hypercapnic perfusion magnetic resonance imaging (MRI). We sought to further evaluate potential hemodynamic restriction in patients with MS using functional sonographic methods. METHODS: We evaluated consecutive patients with MS and healthy controls with adequate bilateral transtemporal window. CVR was assessed by bilateral transcranial Doppler monitoring of proximal middle cerebral arteries. Mean flow velocities were recorded before and after 30 seconds of breath holding. Vasomotor response was quantified by breath holding index (BHI). RESULTS: A total of 42 patients with MS (mean age 39 ± 12 years; 69% women) were compared to 31 healthy controls (mean age 35 ± 11 years; 71% women). BHI was lower in patients with MS compared to healthy controls (.70 ±.43 vs.93 ±.55; P =.006), documenting a lower cerebrovascular response to hypercapnia. There was no correlation between patient age (r =.1254; P =.277), expanded disability status scale (r =.1838; P =.109), and disease duration (r =.1882; P =.101) with BHI in patients with MS. CONCLUSIONS: These preliminary sonographic findings appear to independently corroborate the previously reported observation of impaired CVR on brain MRI in patients with MS. However, the underlying pathophysiological mechanisms as well as the clinical impact of this observation remain elusive. © 2019 by the American Society of Neuroimaging

There is mounting evidence supporting infection as an independent risk factor for ischemic stroke (IS), while preliminary data indicate that vaccination may prevent IS. We performed a systematic review and meta-analysis of available randomized clinical trials (RCTs) or prospective observational cohorts reporting associations of influenza vaccination (IV) and/or pneumococcal vaccination (PV) with IS. We identified a total of 12 studies (543,311 patients; 47.4% vaccinated). Vaccination was not related to the risk of IS (RR = 1.06, 95%CI: 0.74–1.51, p = 0.77), with no significant differences (p = 0.26) among RCTs (RR = 0.66, 95%CI: 0.30–1.47) and observational studies (RR = 1.11, 95%CI: 0.76–1.61). Evidence of considerable heterogeneity was identified within observational studies (I 2 = 98%), but not within RCTs (I 2 = 0%). In subgroup analyses according to vaccination type, IV was associated with a significantly lower risk of IS (RR = 0.87, 95%CI: 0.79–0.96, p = 0.004) with moderate evidence of heterogeneity (I 2 = 53%). No association was seen for PV (RR = 1.38, 95%CI: 0.60–3.16, p = 0.45), where considerable heterogeneity was identified (I 2 = 97%). In the additional adjusted analyses of observational studies, vaccination tended to be associated with lower risk of IS (HRadjusted = 0.87; 95%CI: 0.75–1.01; p = 0.07). The findings of this meta-analysis indicate that IV may be associated with a lower risk of IS. This association was not reproduced for PV or the combination of two vaccines. Substantial heterogeneity was detected across observational studies for all outcome events, while moderate to low heterogeneity was identified across included RCTs. These preliminary findings require independent validation in large RCTs. © 2018 Elsevier B.V.

OBJECTIVE: Current guidelines report no benefit for patent foramen ovale (PFO) closure compared to medical treatment in patients with cryptogenic ischemic stroke (IS) or TIA. Two recent randomized controlled clinical trials have challenged these recommendations. METHODS: We performed a systematic review and network meta-analysis of randomized controlled trials to estimate the safety and efficacy of closure compared to medical treatment, and to compare available devices. We conducted pairwise meta-analyses for closure vs medical therapy, irrespective of the device used, and for each device vs medical therapy. RESULTS: Our literature search highlighted 6 studies. PFO occlusion was associated with reduced risk of recurrent IS (risk ratio [RR] 0.42, 95% confidence interval [CI] 0.20-0.91) and IS/TIA (RR 0.65, 95% CI 0.48-0.88) but with increased risk of new-onset atrial fibrillation (AF) (RR 4.59, 95% CI 2.01-10.45) compared to medical treatment. In indirect analyses, both Amplatzer (AMP) and GORE devices were found to be associated with a lower risk of new-onset AF compared to STARFlex (SFX) (RR 0.25, 95% CI 0.10-0.65 and RR 0.28, 95% CI 0.08-0.95). Moreover, AMP was found to be associated with a lower risk of recurrent IS/TIA events compared to the SFX device (RR 0.35, 95% CI 0.14-0.91). In the clustered ranking plot on the risk of IS against new-onset AF, GORE was comparable to AMP; however, on the risk of IS/TIA against new-onset AF, AMP appeared to be superior to the GORE device. In both ranking plots, SFX was highlighted as the worst option. CONCLUSION: PFO closure is associated with reduced risk of recurrent IS or IS/TIA and with increased risk of new-onset AF. © 2018 American Academy of Neurology.

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

Background and Purpose: The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods: Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of 33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results: Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:−0.415 [95% CI, −0.780 to −0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22−0.85) in multivariable-adjusted models. Conclusions-Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices. © 2018 American Heart Association, Inc.

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.

Background and purpose: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. Methods: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0–1 at 3 months, (iii) functional independence defined as an mRS score of 0–2 at 3 months and (iv) 3-month mortality. Results: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60–140) vs. 65 (IQR, 47–95) min, P < 0.001] and door-to-imaging [40 (IQR, 20–90) vs. 24 (IQR, 15–35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). Conclusions: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS. © 2017 EAN

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.

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.

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.

Background: Although Fingolimod (FGD) and Natalizumab (NTZ) appear to be effective in relapsing-remitting multiple sclerosis (RRMS), they have never been directly compared in a randomized clinical trial (RCT). Methods and Findings: We evaluated the comparative efficacy of FGD vs. NTZ using a meta-analytical approach. Data from placebo-controlled RCTs was used for indirect comparisons and observational data was utilized for head-to-head comparisons. We identified 3 RCTs (2498 patients) and 5 observational studies (2576 patients). NTZ was associated with a greater reduction in the 2-year annualized relapse rate (ARR; SMDindirect = -0.24;95% CI: from -0.44 to -0.04; p = 0.005) and with the probability of no disease activity at 2 years (ORindirect:1.82, 95% CI: from 1.05 to 3.15) compared to FGD, while no differences between the two therapies were found in the proportion of patients who remained relapse-free (ORindirect= 1.20;95% CI: from 0.84 to 1.71) and those with disability progression (ORindirect = 0.76;95% CI: from 0.48 to 1.21) at 2 years. In the analysis of observational data, we found no significant differences between NTZ and FGD in the 2-year ARR (SMD = -0.05; 95% CI: from -0.26 to 0.16), and 2-year disability progression (OR:1.08;95% CI: from 0.77 to 1.52). However, NTZ-treated patients were more likely to remain relapse-free at 2-years compared to FGD (OR: 2.19;95% CI: from 1.15 to 4.18; p = z0.020). Conclusions: Indirect analyses of RCT data and head-to-head comparisons of observational findings indicate that NTZ may be more effective than FGD in terms of disease activity reduction in patients with RRMS. However, head-to-head RCTs are required to independently confirm this preliminary observation. © 2016 Tsivgoulis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11-0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03-0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments. © The Author(s), 2016.

Thyroid hormones (TH) and receptors (TRs) may play an important role in the pathophysiology of acute cerebral ischemia. In the present study, we sought to determine whether serum triodothyronine (T3)/thyroxine (T4) and brain TRs (TRα1, TRβ1) might change after experimental stroke. Male adult Wistar rats were subjected to permanent middle cerebral artery occlusion (group P) and compared to sham-operated controls (group S). Animals were followed clinically for 14 days until brain collection for Western blot (WB) or neuropathological analysis of TRs in three different brain areas (infarcted tissue, E1; noninfarcted ipsilateral hemisphere, E2; and contralateral hemisphere, E3). Analysis of serum TH levels showed a reduction of T4 in group P (p∈=∈0.002) at days 2 to 14, while half of the animals also displayed "low T3" values (p∈=∈0.012) on day 14. This T4 reduction was inversely correlated to the clinical severity of stroke and the concomitant body weight loss (p∈