Early recurrent ischemic lesions in patients with cryptogenic stroke and patent foramen ovale: an observational study

Background: Randomized controlled trials indicate that patent foramen ovate (PFO) closure reduces risk of stroke recurrence in patients with cryptogenic stroke and PFO. However, the optimal time point for PFO closure is unknown and depends on the risk of stroke recurrence. Objective: We aimed to investigate risk of early new ischemic lesions on cerebral magnetic resonance imaging (MRI) in cryptogenic stroke patients with and without PFO. Methods: Cryptogenic stroke patients underwent serial MRI examinations within 1 week after symptom onset to detect early new ischemic lesions. Diffusion-weighted imaging (DWI) lesions were delineated, co-registered, and analyzed visually for new hyperintensities by raters blinded to clinical details. A PFO was classified as stroke-related in patients with PFO and a Risk of Paradoxical Embolism (RoPE) score >5 points. Results: Out of 80 cryptogenic stroke patients, risk of early recurrent DWI lesions was not significantly different in cryptogenic stroke patients with and without PFO. Similar results were observed in patients <= 60 years of age. Patients with a stroke-related PFO even had a significantly lower risk of early recurrent ischemic lesions compared to all other patients with cryptogenic stroke (unadjusted odds ratio 0.23 [95% confidence interval 0.06-0.87], P = 0.030). Conclusion: Our data argue against a high risk of early stroke recurrence in patients with cryptogenic stroke and PFO

Cerebral microbleeds and treatment effect of intravenous thrombolysis in acute stroke: an analysis of the WAKE-UP randomized clinical trial

Background and Objectives: Cerebral microbleeds (CMBs) are common in acute ischemic stroke patients and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown. Methods: We performed a pre-specified analysis of the prospective randomized controlled multicenter WAKE-UP trial including patients with acute ischemic stroke with unknown time of symptom onset and DWI-FLAIR mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with intravenous thrombolysis with alteplase at 0.9 mg / kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by three raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale score (mRS)≤1, and symptomatic intracerebral hemorrhage (ICH) according to NINDS trial criteria 22 to 36 hours after treatment. Results: Of 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis; 98 (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB, 37 (8.1%) had 2-4 CMBs, and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a non-significant increased risk of symptomatic ICH (11.2% versus 4.2%; adjusted odds ratio 2.32 [95% CI 0.99-5.43]; P=.052), but had no effect on functional outcome at 90 days (mRS≤1: 45.8% versus 50.7%; adj. OR 0.99 [0.59-1.64]; P=.955). Patients receiving alteplase had better functional outcome (mRS≤1: 54.6% versus 44.6%, adj. OR 1.61 [1.07-2.43], P=.022) without evidence of heterogeneity in relation to CMB presence (P value of the interactive term .546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy-related) or non-strictly-lobar CMB distribution. Discussion: In the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in acute ischemic stroke patients with one or more CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm-ratio in patients with a larger number of CMBs. Trial registration: ClinicalTrials.gov number, NCT01525290 (https://clinicaltrials.gov/ct2/show/NCT01525290); EudraCT number, 2011-005906-32 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005906-32/GB). Classification of Evidence: This study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and DWI-FLAIR mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days

New remote cerebral microbleeds in acute ischemic stroke: an analysis of the randomized, placebo-controlled WAKE-UP trial

No abstract available

Early New Ischemic Lesions Located Outside the Initially Affected Vascular Territory Appear More Often in Stroke Patients with Elevated Glycated Hemoglobin (HbA1c)

BackgroundEarly new ischemic lesions are common in patients with an acute ischemic stroke. These new ischemic lesions may represent the natural course of the initial stroke or de novo events.ObjectiveWe hypothesized that early new ischemic lesions located outside the initially affected vascular territory would point at de novo events. Therefore, we differentiated new ischemic lesions located outside the initially affected vascular territory from those occurring only inside the initially affected vascular territory to identify risk factors that are associated with de novo events.MethodsStroke patients underwent three magnetic resonance imaging examinations (at 3-T): on admission, on the next day and 4–7 days after symptom onset (clinicaltrials.gov: NCT00715533). Diffusion-weighted imaging (DWI) lesions were delineated, coregistered, and then analyzed for new hyperintensities on follow-up examinations by raters blinded to clinical details. Patients were classified as having “new distant lesions” if new DWI lesions appeared outside or both outside and inside the initially affected vascular territory or “new local lesions” if they were only inside.Results115 patients with early new DWI lesions constitute the study population. Sixteen patients (14%) had new distant lesions and 99 patients (86%) had new local lesions. In comparison between patients with new distant and new local lesions, patients with new distant lesions had significantly more often elevated glycated hemoglobin (HbA1c ≥ 6.5%; p = 0.022).ConclusionOur data indicate that patients with elevated HbA1c have an increased risk for new, de novo ischemic lesions in the acute phase after an ischemic stroke

Emergency lumbar puncture in a patient receiving dabigatran after antagonization with idarucizumab — A case report

AbstractIdarucizumab is an antibody fragment which is used to reverse the anticoagulant effects of dabigatran. We report on the first successful use of idarucizumab before performing an emergency lumbar puncture in a patient on effective anticoagulation with dabigatran thought to have infective cerebral disease (such as temporal encephalitis)

Early New Ischemic Lesions Located Outside the Initially Affected Vascular Territory Appear More Often in Stroke Patients with Elevated Glycated Hemoglobin (HbA1c)

Background: Early new ischemic lesions are common in patients with an acute ischemic stroke. These new ischemic lesions may represent the natural course of the initial stroke or de novo events. Objective: We hypothesized that early new ischemic lesions located outside the initially affected vascular territory would point at de novo events. Therefore, we differentiated new ischemic lesions located outside the initially affected vascular territory from those occurring only inside the initially affected vascular territory to identify risk factors that are associated with de novo events. Methods: Stroke patients underwent three magnetic resonance imaging examinations (at 3-T): on admission, on the next day and 4–7 days after symptom onset (clinicaltrials.gov: NCT00715533). Diffusion-weighted imaging (DWI) lesions were delineated, coregistered, and then analyzed for new hyperintensities on follow-up examinations by raters blinded to clinical details. Patients were classified as having “new distant lesions” if new DWI lesions appeared outside or both outside and inside the initially affected vascular territory or “new local lesions” if they were only inside. Results: 115 patients with early new DWI lesions constitute the study population. Sixteen patients (14%) had new distant lesions and 99 patients (86%) had new local lesions. In comparison between patients with new distant and new local lesions, patients with new distant lesions had significantly more often elevated glycated hemoglobin (HbA1c ≥ 6.5%; p = 0.022). Conclusion: Our data indicate that patients with elevated HbA1c have an increased risk for new, de novo ischemic lesions in the acute phase after an ischemic stroke

Data from: Predictors of new remote cerebral microbleeds after intravenous thrombolysis for ischemic stroke

Objective: To assess the frequency, associated factors, and underlying vasculopathy of new remote cerebral microbleeds (CMB), as well as the risk of concomitant hemorrhagic complications related to new CMBs, after intravenous thrombolysis (IVT) in acute stroke patients. Methods: We conducted an observational study using data from our local thrombolysis registry. We included consecutive stroke patients with MRI (3-Tesla)-based IVT and a follow-up MRI the next day between 2008–2017 (n=396). Only CMBs located outside of the ischemic lesion(s) were considered. We also performed a meta-analysis on new CMBs after IVT that included two additional studies. Results: In our cohort, new remote CMBs occurred in 16/396 patients (4.0%) after IVT and the distribution was strictly lobar in 13/16 patients (81%). Patients with pre-existing CMBs with a strictly lobar distribution were significantly more likely to have new CMBs after IVT (p=0.014). In the random-effects meta-analysis (n=741), the pooled cumulative frequency of new CMBs after IVT was 4.4%. A higher pre-existing CMB burden (>2) was associated with a higher likelihood of new CMBs (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.3–10.3) and new CMBs were associated with the occurrence of remote parenchymal hemorrhage (OR 28.8, 95%CI 8.6–96.4). Conclusions: New remote CMBs after IVT occurred in 4% of stroke patients, mainly had a strictly lobar distribution, and were associated with IVT-related hemorrhagic complications. Pre-existing CMBs with a strictly lobar distribution and a higher CMB burden were associated with new CMBs after IVT, which may indicate an underlying cerebral amyloid angiopathy