Search

Background: In patients with coronary artery disease and concomitant asymptomatic severe carotid stenosis, combined simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA) has been widely performed despite lack of evidence from randomized trials. We recently showed that the risk of stroke or death within 30 days was higher following CABG+CEA compared with CABG alone. Here, we report long-term outcomes following CABG with versus without CEA. Methods: The CABACS (Coronary Artery Bypass Graft Surgery in Patients With Asymptomatic Carotid Stenosis Study) is a randomized, controlled, multicenter, open trial. Patients with asymptomatic severe (≥70%) carotid stenosis undergoing CABG were allocated either CABG+CEA or CABG alone, and follow-up was 5 years. Major secondary end points included nonfatal stroke or death, any death and any nonfatal stroke. Due to low recruitment, the study was stopped prematurely after randomization of 127 patients in 17 centers. Results: By 5 years, the rate of stroke or death did not significantly differ between groups (CABG+CEA 40.6% [95% CI, 0.285–0.536], CABG alone 35.0% [95% CI, 0.231–0.484]; P =0.58). Higher albeit statistically nonsignificant rates of nonfatal strokes occurred at any time following CABG+CEA versus CABG alone (1 year: 19.3% versus 7.1%, P =0.09; 5 years: 29.4% versus 18.8%, P =0.25). All-cause mortality up to 5 years was similar in both groups (CABG+CEA: 25.4% versus CABG alone: 23.3%, hazard ratio, 1.148 [95% CI, 0.560–2.353]; P =0.71). Subgroup analyses did not reveal any significant effect of age, sex, preoperative modified Rankin Scale and center on outcome events. Conclusions: During 5-years follow-up, combined simultaneous CABG+CEA was associated with a higher albeit statistically nonsignificant rate of stroke or death compared with CABG alone. This was mainly due to a nonsignificantly higher perioperative risk following CABG+CEA. Since the power of our study was not sufficient, no significant effect of either procedure could be observed at any time during follow-up. Registration: URL: http://www.controlled-trials.com ; Unique identifier: ISRCTN13486906.

Background: To evaluate the technical results of an arterial repair, a variety of intraoperative imaging and assessment techniques can be used during carotid endarterectomy (CEA). The aim of the study was to evaluate the usefulness of intraoperative ultrasound flow measurement as a quality control after primary CEA in a teaching hospital setting. Methods: Over 36 months, 107 consecutive CEAs were performed at our institution. Retrospectively acquired demographics, intraoperative flow measurements, duplex results, revisions, and surgical outcomes were reviewed. Postoperative 30-day transient ischemic attack (TIA), stroke, and death rates were analyzed. Results were compared with ultrasound flow measurement and duplex ultrasonography. Results: From March 2012 to March 2015, 107 primary consecutive CEAs were performed in 107 patients (71% male, 29% female), whose age ranged from 51 to 81 years with a mean age of 68 ± 4 years. Associated risk factors included diabetes for 89 (83%), smoking for 92 (86%), hypertension for 94 (87.8%), chronic renal insufficiency for 71 (66%), and coronary artery disease for 57 (53%) of the patients. Early postoperative duplex scans in all 107 patients showed no significant changes from intraoperative findings. The ipsilateral stroke and death rate in this study was 0 (0/107) and the 30-day death and stroke rate was also 0 (0/107), with no significant difference between trainees and senior surgeons. Three patients (2.8%) had flow < 100 mL/Min and two of them were revised after completion of contrast angiography. Conclusions: The findings of this study indicate that the intraoperative flow measurement is an alternative method for detecting technical errors and a tool for quality-control imaging. Especially for trainees, it makes sense to ensure effectiveness of the procedure upon its completion and to assess the technical adequacy of CEA.

Background: Patients with symptomatic internal carotid artery (ICA) stenosis are at high risk of recurrent ischemic stroke and require early interventional treatment and antiplatelet therapy. Increased bleeding rates might counterbalance the periprocedural efficacy of intensified platelet inhibition. We aim to investigate, whether Revacept, a competitive antagonist of glycoprotein VI, adjunct to standard antiplatelet therapy reduces the occurrence of ischemic lesions in patients with symptomatic ICA stenosis. Methods: International, multicenter (16 sites), 3-arm, randomized (1:1:1), double-blind, and placebo-controlled study with parallel groups, including patients with symptomatic ICA stenosis. A single infusion over 20 minutes of either placebo, 40 mg or 120 mg Revacept in addition to guideline-conform antiplatelet therapy was evaluated with regard to the exploratory efficacy end point: Number of new ischemic lesions on diffusion-weighted magnetic resonance imaging after treatment initiation. Main clinical outcome was the combined safety and efficacy end point including any stroke or death, transient ischemic attack, myocardial infarction, coronary intervention, and bleeding complications during follow-up. Results: Out of 160 randomized patients, 158 patients (68±10.1 years, 24% female) received study medication (51 patients placebo, 54 patients 40 mg Revacept and 53 patients 120 mg Revacept) and were followed for 11.2±2.3 months. A total of 1.16 (95% CI, 0.88–1.53)/1.05 (95% CI, 0.78–1.42; P =0.629)/0.63 (95% CI, 0.43–0.93) new diffusion-weighted magnetic resonance imaging lesions per patient were detected in the placebo/40 mg/120 mg Revacept groups, without statistical evidence of a difference. A reduction of the combined safety and efficacy end point during the study period was observed in patients who received 120 mg (HR, 0.46 [95% CI, 0.21–0.99]; P =0.047), but not 40 mg Revacept compared with placebo (HR, 0.72 [95% CI, 0.37–1.42]; P =0.343). Conclusions: Revacept 120 mg reduced the combined safety and efficacy end point in patients with symptomatic ICA stenosis. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01645306.

BackgroundEarly neurological deterioration (END) after endovascular treatment (EVT) in patients with anterior circulation acute ischemic stroke (AIS) is associated with poor outcome. END may remain unexplained by parenchymal hemorrhage (UnEND). We aim to analyze the risk factors of UnEND in the medical management (MM) and EVT arms of the HERMES study.MethodsWe conducted a post-hoc analysis of anterior AIS patients who underwent EVT for proximal anterior occlusions. Risk factors of UnEND, defined as a worsening of ≥4 points between baseline National Institutes of Health Stroke Scale (NIHSS) and NIHSS at 24 hours without hemorrhage, were compared between both arms using mixed logistic regression models adjusted for baseline characteristics. An interaction analysis between the EVT and MM arms for risk factors of UnEND was conducted.ResultsAmong 1723 patients assessable for UnEND, 160 patients experienced an UnEND (9.3%), including 9.1% (78/854) in the EVT arm and 9.4% (82/869) in the MM arm. There was no significant difference in the incidence of UnEND between the two study arms. In the EVT population, independent risk factors of UnEND were lower baseline NIHSS, higher baseline glucose, and lower collateral grade. In the MM population, the only independent predictor of UnEND was higher baseline glucose. However, we did not demonstrate an interaction between EVT and MM for baseline factors as risk factors of UnEND. UnEND was, similarly in both treatment groups, a significant predictor of unfavorable outcome in both the EVT (pConclusionsUnEND is not an uncommon event, with a similar rate which ever treatment arm is considered. In the clinical scenario of AIS due to large vessel occlusion, no patient-related factor seems to increase the risk for UnEND when treated by EVT compared with MM.

The original article has been updated to correct Row 2 of Table 4 “04-Jul” to “4–7”. in press

Background Guillain–Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10–30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. Methods A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: “When counseling patients or surrogates of critically ill patients with Guillain–Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?” Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. Conclusions These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Background Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. Methods A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: “When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?” Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. Results Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. Conclusions These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

Background We hypothesized that stroke outcome is related to multiple baseline hydration‐related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.

Background The optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage. Aim The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation. Design and Methods PRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death. Summary PRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.

Little is known about the impact of long-term ambient air pollution (AP) and noise exposure on change in cognitive function over years in the elderly. In this study, we wanted to examine the association between long-term exposure to AP and noise with the rate of cognitive decline in a population aged 50 and older and susceptible groups with mild cognitive impairment or at a genetically higher risk of Alzheimer's disease (Apolipoprotein E ε4 positive). Participants in the German population-based Heinz Nixdorf Recall study carried out five neuropsychological tests. Individual tests scores at the first (T₁ = 2006–2008) and second (T₂ = 2011–2015) follow-up for each test were used as outcomes after standardization using predicted means adjusted for age and education. Global cognitive score (GCS) was defined as sum of five standardized scores of individual tests. Long-term exposures to particulate matter (PM₂.₅, PM₁₀, PM₂.₅ absorbance), accumulation mode particle number (PNₐcc), a proxy of ultrafine particles, and nitrogen dioxide were estimated by the land-use regression and chemistry transport models. Noise exposures were assessed as outdoor weighted nighttime road traffic noise (Lnight) means. We performed linear regression analyses adjusted for sex, age, individual and neighborhood socio-economic status, and lifestyle variables. Effect modification in vulnerable groups was estimated using multiplicative interaction terms between exposure and a modifier. Overall, 2554 participants (49.5% men, median age is 63 (IQR = 12)) were included. We found weak associations between higher exposure to PM₁₀ and PM₂.₅ with faster decline in the immediate verbal memory test. Adjustment for potential confounders and for co-exposures did not change the results. We saw no effects on GCS, and no effect of noise exposure. In susceptible groups, higher AP and noise exposure were tended to be associated with faster decline in GCS. Our results suggest that AP exposure may accelerate cognitive decline in older ages, particularly in susceptible groups.

Background Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events. Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. Design CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. Outcome The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). Summary CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. Schedule First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

Auch wenn die zerebrale Venen-/Sinusthrombose (CVST) eine seltene zerebrovaskuläre Erkrankung darstellt, wird sie zunehmend häufiger diagnostiziert aufgrund erhöhter klinischer Aufmerksamkeit, besserer Bildgebungsmöglichkeiten sowie einer höheren Überlebensrate von Patienten mit prädisponierenden Erkrankungen. Dieser Beitrag zeigt, wie die Diagnose effektiv gestellt werden kann und welche Therapieoptionen in der Akutphase und Sekundärprophylaxe bestehen.

Background and Purpose: We designed SITS (Safe Implementation of Treatment in Stroke) Open to determine benefit and safety of thrombectomy in clinical practice for large artery occlusion stroke, using selected stent retrievers plus standard care versus standard care alone. Methods: SITS Open was a prospective, open, blinded evaluation, international, multicenter, controlled, nonrandomized registry study. Centers lacking access to thrombectomy contributed controls. Primary end point was categorical shift in modified Rankin Scale score at 3 months in the per protocol (PP) population. Principal secondary outcomes were symptomatic intracranial hemorrhage, functional independency (modified Rankin Scale score 0–2) and death at 3 months. Patients independently evaluated by video-recorded modified Rankin Scale interviews blinded to treatment or center identity by central core laboratory were regarded as PP population. Propensity score matching with covariate adjusted analysis was performed. Results: During 2014 to 2017, 293 patients (257 thrombectomy, 36 control) from 26 centers in 10 countries fulfilled intention-to-treat and 200 (170 thrombectomy, 30 control) PP criteria; enrollment of controls was limited by rapid uptake of thrombectomy. In PP analysis, median age was 71 versus 71 years, and baseline National Institutes of Health Stroke Scale 17 versus 17 in the thrombectomy and control arms, respectively. The propensity score matching analysis for PP showed a significant shift for modified Rankin Scale at 3 months favoring the thrombectomy group (odds ratio, 3.8 [95% CI, 1.61–8.95]; P =0.002). Regarding safety, there were 4 cases of symptomatic intracranial hemorrhage in the thrombectomy group (2.4%) and none in the control group. Conclusions: In clinical practice, thrombectomy for patients with large artery occlusion stroke is superior to standard of care in our study. Registration: URL: https://www.clinicaltrials.gov . Unique Identifier: NCT02326428.

Midlife hypertension is a risk factor for cognitive decline in late-life but little is known about the impact of long-term hypertension on cognitive change over time.We examined blood pressure and cognitive function in 2777 participants (baseline: 2000-2003, 45-75 years, 48.4% men) from the Heinz Nixdorf Recall study. Blood pressure was assessed at three study visits and cognitive function was assessed at both follow-ups (mean follow-up: 5.1 years). Z-score differences in five neuropsychological tests, defining cognitive decline, were derived from linear regression models including age and education. The association of cognitive decline over 5 years and blood pressure over 10 years (classified as: normal blood pressure (10 years, reference), prevalent hypertension (10 years), incident hypertension t1 (5 years), incident hypertension t2 (5 years), temporary hypertension (at least one hypertensive reading)) was calculated using linear regression models resulting in coefficient b and 95% confidence interval. We calculated interactions with age (linear and with a cutoff at 65 years).Participants with prevalent hypertension showed a greater cognitive decline in both verbal memory tests. Incident hypertension t1 was associated with a greater decline in the visuospatial organization test. There was no interaction with age.This study showed that prevalent high blood pressure over 10 years is related to cognitive decline. Prevalent hypertension with longer exposure time may be more detrimental than temporary hypertension for cognitive function.

Introduction Approaches to economic evaluations of stroke therapies are varied and inconsistently described. An objective of the European Stroke Organisation (ESO) Health Economics Working Group is to standardise and improve the economic evaluations of interventions for stroke. Methods The ESO Health Economics Working Group and additional experts were contacted to develop a protocol and a guidance document for data collection for economic evaluations of stroke therapies. A modified Delphi approach, including a survey and consensus processes, was used to agree on content. We also asked the participants about resources that could be shared to improve economic evaluations of interventions for stroke. Results Of 28 experts invited, 16 (57%) completed the initial survey, with representation from universities, government, and industry. More than half of the survey respondents endorsed 13 specific items to include in a standard resource use questionnaire. Preferred functional/quality of life outcome measures to use for economic evaluations were the modified Rankin Scale (14 respondents, 88%) and the EQ-5D instrument (11 respondents, 69%). Of the 12 respondents who had access to data used in economic evaluations, 10 (83%) indicated a willingness to share data. A protocol template and a guidance document for data collection were developed and are presented in this article. Conclusion The protocol template and guidance document for data collection will support a more standardised and transparent approach for economic evaluations of stroke care.

Objective We provide normative data for the Trail Making Test (TMT)-A and B and the derived scores B − A and B/A, for the German general population aged 57–84 years. Methods Data were derived from the third examination of the population-based Heinz Nixdorf Recall study. We excluded participants with a history of dementia or stroke, a depression score above cutoff (CES-D Center for Epidemiologic Studies Depression Scale score ≥ 18), or mild cognitive impairment according to a neurocognitive test battery. The normative sample (n = 2,182) was stratified by age, using the interval superposition approach, and by three levels of educational attainment (up to 10 years of schooling; >10 years of schooling; and university degree). Results We tabulated test performance scores at percentage rank thresholds 5, 10, 15, 20, 25, 50, 75, and 90. In multiple linear regression, TMT-A performance declined by 1 s each year of life, and TMT-B performance by 3 s; educational level had an impact of up to 30 s in TMT-B. TMT-B/A was only weakly associated with age and education. TMT-B and B − A correlated r = 0.96. Completion of the TMT-B within the time limit of 300 s was not achieved by 10.9% of participants >74 years, and especially by those >74 years who were on the lowest educational level (13.9%). Conclusions For TMT-A, TMT-B, and B − A, the narrow age categorization and distinction between three educational levels proved meaningful. The 300 s limit for the TMT-B impedes the identification of thresholds for very low performance in this age group and needs reconsideration.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Emerging evidence from randomized controlled clinical trials (RCTs) suggests that colchicine has cardiovascular benefits for patients with coronary disease, including benefits for stroke prevention. We performed an updated systematic review and meta-analysis of all RCTs reporting on stroke outcomes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). We identified 6 RCTs including a total of 11,870 patients (mean age 63 years, 83% males) with a mean follow-up of 2 years. Colchicine treatment was associated with a lower risk of stroke during follow-up, compared to that of placebo or usual care (risk ratio = 0.49, 95% confidence interval: 0.31–0.80, p = 0.004), without heterogeneity across the included studies (I2 = 0%, p for Cochran’s Q = 0.52). In the subgroup analysis, no heterogeneity (p = 0.77) was identified in the effect of colchicine on stroke prevention between patients with recent acute (RR = 0.55, 95% CI: 0.15–2.05) or chronic stable (RR = 0.43, 95% CI: 0.21–0.89) coronary artery syndromes. In conclusion, we found that colchicine treatment decreases the stroke risk in patients with a history of atherosclerotic cardiovascular disease.

The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

Auch wenn die zerebrale Venen-/Sinusthrombose (CVST) eine seltene zerebrovaskulare Erkrankung darstellt, wird sie zunehmend haufiger diagnostiziert aufgrund erhohter klinischer Aufmerksamkeit, besserer Bildgebungsmoglichkeiten sowie einer hoheren Uberlebensrate von Patienten mit pradisponierenden Erkrankungen. Dieser Beitrag zeigt, wie die Diagnose effektiv gestellt werden kann und welche Therapieoptionen in der Akutphase und Sekundarprophylaxe bestehen.

Although cerebral venous and sinus thrombosis (CVST) is a rare cerebrovascular disease, it is being diagnosed with increasing frequency due to increased clinical awareness, better imaging capabilities, and higher survival rates in patients with predisposing conditions. This article shows how the diagnosis can be made effectively and what therapeutic options exist in the acute phase and secondary prophylaxis.Auch wenn die zerebrale Venen-/Sinusthrombose (CVST) eine seltene zerebrovaskuläre Erkrankung darstellt, wird sie zunehmend häufiger diagnostiziert aufgrund erhöhter klinischer Aufmerksamkeit, besserer Bildgebungsmöglichkeiten sowie einer höheren Überlebensrate von Patienten mit prädisponierenden Erkrankungen. Dieser Beitrag zeigt, wie die Diagnose effektiv gestellt werden kann und welche Therapieoptionen in der Akutphase und Sekundärprophylaxe bestehen.

Background There is an under-recognised patient cohort at elevated risk of postoperative ischaemic stroke. We aimed to develop and validate a prognostic model for the identification of such patients at high risk of ischaemic stroke within 1 yr after noncardiac surgery. Methods This was a hospital registry study of adult patients undergoing noncardiac surgery between 2005 and 2017 at two independent healthcare networks in Massachusetts, USA without a preoperative indication for therapeutic anticoagulation. Logistic regression was used to fit a model from a priori defined candidate predictors for the outcome 1 yr postoperative ischaemic stroke. To enhance clinical applicability, the model was simplified to a scoring system and externally validated. Results In the development (n=107 756) and validation (n=141 724) cohorts, 1.4% and 0.5% of patients had an ischaemic stroke up to 1 yr postoperatively. The final model included 13 variables (patient characteristics, comorbidities, procedural factors), considering sub-models conditional on a previous history of ischaemic stroke. Areas under the curve were 0.89 (95% confidence interval 0.89–0.90) and 0.88 (95% confidence interval 0.86–0.89) in the development and validation cohorts. Decision curve analysis indicated positive net benefits superior to other prediction instruments. Conclusions Stroke after surgery (STRAS) screening can reliably identify patients with a high risk for ischaemic stroke during the first year after surgery. A STRAS-guided risk stratification may inform the recruitment to future randomised trials testing the efficacy of treatments for the prevention of postoperative ischaemic stroke.

Background: The apolipoprotein E (APOE) ɛ4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. Objective: To investigate whether APOE ɛ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. Methods: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOE ɛ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. Results: Indication for interaction on the additive scale was found between APOE ɛ4 and low education on MCI (RERI: 0.52 [95% confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOE ɛ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. Conclusion: Results indicate that low education may have an impact on APOE ɛ4 expression on MCI, especially among women.

Digital, Objective Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. Methods We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Results Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (pheterogeneity, Ciencias Médicas y de la Salud

[Background] Cerebral venous thrombosis (CVT) is associated with intracranial hemorrhage., [Aim] To identify clinical and imaging features of CVT-associated intracranial hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracranial hemorrhage., [Methods] We performed a retrospective analysis of an international, multicenter cohort of patients with confirmed cerebral venous thrombosis who underwent computed tomography within 2 weeks of symptom onset. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging., [Results] We enrolled 260 patients from 10 institutions in Europe and Mexico. The mean age was 42 years and 74% were female. Intracranial hemorrhage was found in 102 (39%). Among them parenchymal hemorrhage occurred in 64 (63%), in addition, small juxta-cortical hemorrhage was found in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Multiple concomitant types of hemorrhage occurred in 23 (23%). Older age and superior sagittal thrombosis involvement were associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracranial hemorrhage (median number IQRInterquartile ratio] of sinuses/veins involved with hemorrhage 2 (1–3) vs. 2 (1–3) without hemorrhage, p = 0.4)., [Conclusion] The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with higher bleeding risk.

Associations of sleep characteristics with mild cognitive impairment (MCI) have been examined in cross-sectional, but rarely in longitudinal studies. Incident MCI and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a population-based cohort study in Germany (age at first follow-up 50-80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including PSQI (Pittsburgh Sleep Quality Index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing MCI when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. Poor sleep quality (PSQI > 5) (RR = 1.43, 95% CI: 1.12-1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94-2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to

BACKGROUND AND PURPOSE: Although clinical trials suggest that colchicine may reduce the risk of vascular events in patients with a history of coronary artery disease, its effect on the prevention of cerebrovascular events still remains unclear. METHODS: A systematic review and meta-analysis was performed of all available randomized controlled trials (RCTs) reporting on incident strokes during the follow-up of patients with a history of cardiovascular disease randomized to colchicine treatment or control (placebo or usual care). RESULTS: Four RCTs were identified, including a total of 5553 patients (mean age 61 years, 81% males), with a follow-up ranging from 1 to 36 months. Colchicine treatment was associated with a significantly lower risk of incident stroke during follow-up compared to control (risk ratio 0.31, 95% confidence interval 0.13-0.71), without heterogeneity across included studies (I2 = 0%). Based on the pooled incident stroke rate of control groups (0.9%) in the included RCTs, it was estimated that administration of low-dose colchicine to 161 patients with coronary artery disease would prevent one stroke during a follow-up of 23 months. CONCLUSION: Colchicine treatment decreases stroke risk in patients with a history of coronary artery disease. The effect of colchicine in secondary stroke prevention is currently being evaluated in an ongoing RCT. ispartof: EUROPEAN JOURNAL OF NEUROLOGY vol:27 issue:6 pages:1035-1038 ispartof: location:England status: published