The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).

Objective: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes.Methods: This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months.Results: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2–11]) compared with VKA (6, [2–14]) and controls (7, [3–15], p < 0.001; quantile regression: β −2.1, 95% confidence interval [CI] −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51).Interpretation: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53

BACKGROUND AND PURPOSE: Spine MR imaging plays a pivotal role in the diagnostic work-up of spontaneous intracranial hypotension. The aim of this study was to compare the diagnostic accuracy of unenhanced spine MR imaging and intrathecal gadolinium-enhanced spine MR imaging for identification and localization of CSF leaks in patients with spontaneous intracranial hypotension. MATERIALS AND METHODS: A retrospective study of patients with spontaneous intracranial hypotension examined from February 2013 to October 2017 was conducted. Their spine MR imaging was reviewed by 3 blinded readers for the presence of epidural CSF using 3 different sequences (T2WI, 3D T2WI fat-saturated, T1WI gadolinium). In patients with leaks, the presumed level of the leak was reported. RESULTS: In total, 103 patients with spontaneous intracranial hypotension (63/103 [61%] women; mean age, 50 years) were evaluated. Seventy had a confirmed CSF leak (57/70 [81%] proved intraoperatively), and 33 showed no epidural CSF on multimodal imaging. Intrathecal gadolinium-enhanced spine MR imaging was nonsuperior to unenhanced spine MR imaging for the detection of epidural CSF (P = .24 and .97). All MR imaging sequences had a low accuracy for leak localization. In all patients, only 1 leakage point was present, albeit multiple suspicious lesions were reported in all sequences (mean, 5.0). CONCLUSIONS: Intrathecal gadolinium-enhanced spine MR imaging does not improve the diagnostic accuracy for the detection of epidural CSF. Thus, it lacks a rationale to be included in the routine spontaneous intracranial hypotension work-up. Heavily T2-weighted images with fat saturation provide high accuracy for the detection of an epidural CSF collection. Low accuracy for leak localization is due to an extensive CSF collection spanning several vertebrae (false localizing sign), lack of temporal resolution, and a multiplicity of suspicious lesions, albeit only a single leakage site is present. Thus, dynamic examination is mandatory before targeted treatment is initiated.

Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

BACKGROUND: Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown. METHODS: This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms. RESULTS: Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was −2.2% (95% CI, −7.8% to 3.5%) in people with HT (HI: −4.7% [95% CI, −10.8% to 1.4%]; PH: 6.1% [95% CI, −8.5% to 20.6%]) and −0.9% (95% CI, −2.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3–6) was 11.5% (95% CI, −0.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, −6.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and −2.6% (95% CI, −7.1% to 1.8%) in people without HT. CONCLUSIONS: We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH. REGISTRATION: URL: http://www.clinicaltrials.gov ; Unique identifier: NCT03148457.