Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

Background and purpose: Although the main clinical features of COVID‐19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID‐19 Task Force initiated a survey on neurological symptoms observed in patients with COVID‐19 infection.Methods: A 17‐question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020.Results: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID‐19 mainly in emergency rooms and in COVID‐19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID‐19 (neuro COVID‐19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID‐19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection.Conclusion: Neurologists are currently and actively involved in the management of neurological issues related to the COVID‐19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID‐19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Objectives: Developing new high relaxivity gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) allowing dose reduction while maintaining similar diagnostic efficacy is needed, especially in the context of gadolinium retention in tissues. This study aimed to demonstrate that contrast-enhanced MRI of the central nervous system (CNS) with gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg, and superior to unenhanced MRI. Materials and Methods: PICTURE is an international, randomized, double-blinded, controlled, cross-over, phase III study, conducted between June 2019 and September 2020. Adult patients with CNS lesions were randomized to undergo 2 MRIs (interval, 2–14 days) with gadopiclenol (0.05 mmol/kg) then gadobutrol (0.1 mmol/kg) or vice versa. The primary criterion was lesion visualization based on 3 parameters (border delineation, internal morphology, and contrast enhancement), assessed by 3 off-site blinded readers. Key secondary outcomes included lesion-to-background ratio, enhancement percentage, contrast-to-noise ratio, overall diagnostic preference, and adverse events. Results: Of the 256 randomized patients, 250 received at least 1 GBCA administration (mean [SD] age, 57.2 [13.8] years; 53.6% women). The statistical noninferiority of gadopiclenol (0.05 mmol/kg) to gadobutrol (0.1 mmol/kg) was achieved for all parameters and all readers (n = 236, lower limit 95% confidence interval of the difference ≥−0.06, above the noninferiority margin [−0.35], P < 0.0001), as well as its statistical superiority over unenhanced images (n = 239, lower limit 95% confidence interval of the difference ≥1.29, P < 0.0001). Enhancement percentage and lesion-to-background ratio were higher with gadopiclenol for all readers (P < 0.0001), and contrast-to-noise ratio was higher for 2 readers (P = 0.02 and P < 0.0001). Three blinded readers preferred images with gadopiclenol for 44.8%, 54.4%, and 57.3% of evaluations, reported no preference for 40.7%, 21.6%, and 23.2%, and preferred images with gadobutrol for 14.5%, 24.1%, and 19.5% (P < 0.001). Adverse events reported after MRI were similar for gadopiclenol (14.6% of patients) and gadobutrol (17.6%). Adverse events considered related to gadopiclenol (4.9%) and gadobutrol (6.9%) were mainly injection site reactions, and none was serious. Conclusions: Gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg for MRI of the CNS, confirming that gadopiclenol can be used at half the gadolinium dose used for other GBCAs to achieve similar clinical efficacy.

Patients with noncardioembolic ischemic stroke or transient ischemic attack (TIA) are at risk for recurrent stroke. Low factor XI levels are associated with a reduced risk of ischemic stroke. Asundexian inhibits activated factor XI. Whether the addition of asundexian to antiplatelet therapy would be superior to antiplatelet therapy alone for the secondary prevention of ischemic stroke is unclear. In this phase 3, double-blind trial, we randomly assigned patients within 72 hours after the onset of a noncardioembolic ischemic stroke or high-risk TIA to receive asundexian (50 mg once daily) or placebo, in addition to planned dual or single antiplatelet therapy. Patients had at least one of the following: a nonlacunar infarct on imaging, a history of atherosclerosis, or evidence of atherosclerotic plaque at any location on cerebrovascular imaging. The primary efficacy outcome was ischemic stroke. The composite of death from cardiovascular causes, myocardial infarction, or stroke was a key secondary outcome. The primary safety outcome was major bleeding. Among 12,327 patients who underwent randomization (6162 to the asundexian group and 6165 to the placebo group), the incidence of ischemic stroke was lower in the asundexian group than in the placebo group (6.2% vs. 8.4%; cause-specific hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.84; P<0.001). The incidence of the composite of death from cardiovascular causes, myocardial infarction, or stroke was lower in the asundexian group than in the placebo group. The incidence of major bleeding was similar in the asundexian group and the placebo group (1.9% and 1.7%, respectively; cause-specific hazard ratio, 1.10; 95% CI, 0.85 to 1.44). The incidence of adverse events was 69.3% in the asundexian group and 70.1% in the placebo group; the incidence of serious adverse events was 19.2% and 19.5%, respectively. Among patients with noncardioembolic ischemic stroke or high-risk TIA treated with antiplatelet therapy, asundexian at a daily dose of 50 mg resulted in lower risks of ischemic stroke and major cardiovascular events than placebo, without a higher risk of major bleeding. (Funded by Bayer; OCEANIC-STROKE ClinicalTrials.gov number, NCT05686070.).