Abstract only Background: Delays in the prehospital phase jeopardize the chances for stroke patients to be treated with thrombolysis. However, the causes of prehospital delay remain obscure. We ...assessed the causes of prehospital delay among patients with acute ischemic stroke. Methods: In this prospective cohort study, we included patients admitted to the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischemic stroke. A corresponding positive Diffusion Weighted Imaging MR was required to be included in the study, i.e. patients with no or negative DWI-MR were excluded. Trained study nurses interviewed all patients or their proxies in person at the bedside. The study period spanned from September, 2015 to July, 2017. Results: Overall, 321 patients were included. The median NIHSS score was 3 (interquartile range IQR: 1-5). Median delay between symptom onset and call for help was 55 minutes (IQR: 10-420). The mode of transportation to the Stroke Center was with paramedics (ambulance or helicopter) for 60 % of patients, without in 40% (private car: n=72; taxi: n=31; public transportation, walk-in or other: n=25). NIHSS was higher in patients transported with paramedics (4 IQR 2-6 vs. 1.5 0-3, P <0.001). A family physician was consulted immediately prior to hospitalization by 11% of patients (n=35), 89% were admitted directly to the hospital, and the difference in NIHSS was not statistically significant. The thrombolysis ratio was 25%. After adjusting for NIHSS, the odds of thrombolysis were higher among patients transported with paramedics (adjusted odds ratio aOR: 2.4, 95%-CI: 1.2-4.7, P=0.01), and lower among patients with prior family physician consultation (aOR: 0.10, 95%-CI: 0.01-0.77, P =0.03). Conclusions: One out four patients wait 7 hours or more before calling for help, a considerable delay. Transport with paramedics was associated with increased chances of thrombolysis. One in ten patients consulted a family physician immediately prior to hospitalization, reducing by 90 percent points the chances of thrombolysis. Identifying and informing family physicians who see patients with symptoms of an acute stroke may be a so far underestimated, cost-effective measure to increase the rate of thrombolysis.
BACKGROUND AND OBJECTIVESThe neuroprotectant nerinetide has shown promise in reducing infarct volumes in primate models of ischemia reperfusion. We hypothesized that early secondary infarct growth ...after endovascular therapy (EVT) (1) may be a suitable surrogate biomarker for testing neuroprotective compounds, (2) is feasible to assess in the acute setting using sequential MRI, and (3) can be modified by treatment with nerinetide.METHODSREPERFUSE-NA1 was a prospective, multisite MRI substudy of the randomized controlled trial ESCAPE-NA1 (ClinicalTrials.gov NCT02930018) that involved patients with acute disabling large vessel occlusive stroke undergoing EVT within 12 hours of onset who were randomized to receive intravenous nerinetide or placebo. Patients enrolled in REPERFUSE-NA1 underwent sequential MRI <5 hours post-EVT (day 1) and at 24 hours (day 2). The primary outcome was total diffusion-weighted MRI infarct growth early after EVT, defined as the lesion volume difference between day 2 and day 1. The secondary outcome was region-specific infarct growth in different brain tissue compartments. Statistical analyses were performed using the Mann-Whitney U test and multiple linear regression.RESULTSSixty-seven of 71 patients included had MRI of sufficient quality. The median infarct volume post-EVT was 12.98 mL (IQR, 5.93-28.08) in the nerinetide group and 10.80 mL (IQR, 3.11-24.45) in the control group (p = 0.59). Patients receiving nerinetide showed a median early secondary infarct growth of 5.92 mL (IQR, 1.09-21.30) compared with 10.80 mL (interquartile range IQR, 2.54-21.81) in patients with placebo (p = 0.30). Intravenous alteplase modified the effect of nerinetide on region-specific infarct growth in white matter and basal ganglia compartments. In patients with no alteplase, the infarct growth rate was reduced by 120% (standard error SE, 60%) in the white matter (p = 0.03) and by 340% (SE, 140%) in the basal ganglia (p = 0.02) in the nerinetide group compared with placebo after adjusting for confounders.DISCUSSIONThis study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acute stroke treatment. Patients with acute large vessel occlusive stroke exhibited appreciable early infarct growth both in the gray matter and the white matter after undergoing EVT. Acknowledging relatively small overall infarct volumes in this study, treatment with nerinetide was associated with slightly reduced percentage infarct growth in the white matter and basal ganglia compared with placebo in patients not receiving intravenous alteplase and had no effect on the total early secondary infarct growth.TRIAL REGISTRATION INFORMATIONClinicalTrials.gov NCT02930018.CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that for patients with acute large vessel ischemic stroke undergoing EVT, nerinetide did not significantly decrease early post-EVT infarct growth compared with placebo.
Background:
Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce.
Methods:
We used prospectively obtained data from an observational registry ...(Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed.
Results:
Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR 95% CI 1.64 1.11, 2.40, p = 0.017) and recurrent IS (aHR 2.96 1.65, 5.35 , p < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause.
Conclusion:
In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients.
Clinical Trial Registration:
NCT 03826927
Graphical abstract
Introduction
Cerebral small vessel disease is an important cause for both ischaemic stroke and intracranial haemorrhage. To date, knowledge on the impact of small vessel disease on the clinical ...course in stroke patients treated with oral anticoagulation for atrial fibrillation is limited.
Patients and Methods
Registry-based prospective observational study of 320 patients (aged 78.2 ± 9.2 years) treated with anticoagulation following atrial fibrillation stroke. Patients underwent standardised magnetic-resonance-imaging assessing measures of small vessel disease, including cerebral microbleeds and white matter hyperintensities. Median follow-up was 754 (interquartile range = 708–828) days. Using adjusted logistic and Cox regression, we assessed the association of imaging measures with clinical outcome including recurrent ischaemic stroke, intracranial haemorrhage and death and assessed disability (modified Rankin Scale).
Results
Overall, recurrent ischaemic stroke was more common than intracranial haemorrhage (22 versus 8, respectively). Cerebral microbleeds were related to an increased risk of the composite endpoint (ischaemic stroke, intracranial haemorrhage, death: odds ratio (OR) 2.05, 95% confidence interval (CI) 1.27–3.31; P = 0.003), as were white matter hyperintensities (OR 2.00, 95%CI 1.23–3.27, P = 0.005). This was also true in time-to-event analysis (cerebral microbleeds: HR 2.31, 95%CI 1.39–3.52; P < 0.001; white matter hyperintensities: HR 1.99, 95%CI 1.20–3.17; P = 0.007). Both measures were associated with an increased risk for recurrent ischaemic stroke (cerebral microbleeds: HR 4.42, 95%CI 1.07–18.20; P = 0.04; white matter hyperintensities: HR 5.27, 95%CI 1.08–25.79, P = 0.04) and intracranial haemorrhage (cerebral microbleeds: HR 2.43, 95%CI 1.04–5.69; P = 0.04; white matter hyperintensities: HR 2.57, 95%CI 1.11–5.98, P = 0.03). Furthermore, confluent white matter hyperintensities were associated with increased disability (OR 4.03; 95%CI 2.16–7.52; P < 0.001) and mortality (HR 1.81, 95%CI 1.04–3.14, P = 0.04).
Discussion and conclusion
In atrial fibrillation stroke patients treated with oral anticoagulation, small vessel disease is associated with an unfavourable outcome. The presence of microbleeds indicated a risk higher for recurrent ischaemic stroke than for intracranial haemorrhage.
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