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Background and purpose Recurrent ischemic stroke (IS) or TIA is frequent with a considerable variation in incidence and mortality across populations. Current data on stroke recurrence and mortality are useful to examine trends, risk factors, and treatment effects. In this study, we calculated the incidence of recurrent IS or TIA in a hospital‐based stroke population in Western Norway, investigated recurrence factors, and estimated the effect of recurrence on all‐cause mortality. Methods This prospective cohort study registered recurrence and mortality among 1872 IS and TIA survivors admitted to the stroke unit at Haukeland University Hospital between July 2007 and December 2013. Recurrence and death until September 1, 2016, were identified by medical chart review. Cumulative incidences of recurrence were estimated with a competing risks Cox model. Multivariate Cox models were used to examine recurrence factors and mortality. Results During follow‐up, 220 patients had 277 recurrent IS or TIAs. The cumulative recurrence rate was 5.4% at 1 year, 11.3% at 5 years, and 14.2% at the end of follow‐up. Hypertension (HR = 1.65, 95% CI 1.21‐2.25), prior symptomatic stroke (HR = 1.63, 95% CI 1.18‐2.24), chronic infarcts on MRI (HR = 1.48, 95% CI 1.10‐1.99), and age (HR 1.02/year, 95% CI 1.00‐1.03) were independently associated with recurrence. A total of 668 (35.7%) patients died during follow‐up. Recurrence significantly increased the all‐cause mortality (HR = 2.55, 95% CI 2.04‐3.18). Conclusions The risk of recurrent IS stroke or TIA was modest in our population and was associated with previously established risk factors. Recurrence more than doubled the all‐cause mortality.

Background and Purpose: Ischemic stroke can be the first manifestation of cancer and it is therefore important to ascertain which stroke patients should be considered for cancer-diagnostic investigations. We aimed to determine the frequency of active cancer in patients with acute ischemic stroke and to compare clinical findings in stroke patients with active cancer to ischemic stroke patients with no history of cancer. Finally, we aimed to develop a predictive and feasible score for clinical use to uncover underlying malignancy. Methods: All ischemic stroke patients admitted to the stroke unit in the Department of Neurology, Haukeland University Hospital were consecutively included in the Norwegian Stroke Research Registry (NORSTROKE). Stroke etiology was determined by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Data on cancer diagnoses was obtained from patients’ medical records and the Cancer Registry of Norway. Active cancer was defined as cancer diagnosis, metastasis of known cancer, recurrent cancer or receiving cancer treatment, all within 12 months before or after the index stroke. Based on variables independently associated with active cancer, a predictive score was developed using the area under the receiver operating characteristic (AUC-ROC) curves. Bayes’ theorem was used to calculate post-test probabilities of active cancer. Results: Of the 1,646 ischemic stroke patients included, 82 (5.0%) had active cancer. Increased D-dimer (OR = 1.1, 95% CI: 1.1–1.2, p = <0.001), lower Hb (OR = 0.6, 95% CI: 0.5–0.7, p = <0.001), smoking (OR = 2.2, 95% CI: 1.2–4.3, p = 0.02) and suffering a stroke of undetermined etiology (OR = 1.9, 95% CI: 1.1–3.3, p = 0.03) were factors independently associated with active cancer. These were included in the final predictive score which gave an AUC of 0.73 (95% CI: 0.65–0.81) in patients younger than 75 years of age. Assuming the prevalence of cancer to be 5%, the score shows that if a patient fulfills all 3 score points, the probability of active cancer is 53%. Conclusions: Active cancer was found in 5% of our ischemic stroke patients. We found that a clinical score comprising elevated D-dimer ≥3 mg/L, lower Hb ≤12.0 g/dL and previous or current smoking is feasible for predicting active cancer in ischemic stroke patients.

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Given that alteplase has been the only approved thrombolytic agent for acute ischemic stroke for almost two decades, there has been intense interest in more potent and safer agents over the last few years. Tenecteplase is a bioengineered mutation of alteplase with advantageous pharmacodynamics and pharmacokinetics. The superiority of tenecteplase over alteplase has been proven by in vitro and animal studies, and it was approved for use in myocardial infarction more than a decade ago. In patients with acute ischemic stroke, tenecteplase has shown promise in randomized phase II trials and the drug is currently being tested in four phase III clinical trials that will start delivering definite results in the near future: NOR-TEST (NCT01949948), TASTE (ACTRN12613000243718), TEMPO-2 (NCT02398656), and TALISMAN (NCT02180204).

BackgroundAlteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase.Methods/DesignNOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½ hours after symptoms onset; b) admitted <4½ hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0–1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24–48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24–36 hours; 5) death.DiscussionNOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).

Background: Transient elevated blood pressure (BP) is frequent in patients presenting with acute ischemic stroke. The pathophysiology of this response is not clear and its effect on clinical outcome has shown contradictory results. Some studies have suggested that BP elevation may represent a protective response to enhance perfusion in ischemic brain tissue. In this study, we aimed to explore the association between elevated admission BP and stroke severity in the acute phase of ischemic stroke. If it is true that elevated BP represents a protective response in acute ischemia, we expected an inverse association between elevated BP and admission stroke severity, and a positive association between elevated BP and complete neurological recovery within 24 h and/or favorable short-term outcome. Methods: Patients with ischemic stroke with hospital admission <6 h after symptom onset were prospectively included in a stroke registry (Bergen NORSTROKE Registry). BP was measured immediately after admission in all patients. Elevated BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Mild stroke was defined as NIHSS score <8, moderate stroke as NIHSS score 8-14, and severe stroke as NIHSS score ≥15. Complete neurological recovery (CNR) was defined as no persistent ischemic stroke symptoms at 24 h after admission. Favorable short-term outcome was defined as a modified Rankin Scale score of 0 or 1 at day 7. Results: A total of 749 patients with ischemic stroke were included, of which 621 patients (82.9%) presented with elevated BP. Elevated BP was independently associated with mild stroke (odds ratio, OR: 2.12; 95% CI: 1.39-3.24; p < 0.001), whereas lack of elevated BP was independently associated with severe stroke (OR: 0.41; 95% CI: 0.25-0.68; p < 0.001). There was a nonsignificant association between elevated BP and CNR (OR: 2.11; 95% CI: 0.96-4.68; p = 0.063), yet no association between elevated BP and favorable short-term outcome (OR: 0.97; 95% CI: 0.59-1.59; p = 0.906) when adjusted for confounders. Conclusion: Our study showed an inverse association between elevated BP and stroke severity on admission, where elevated BP was associated with mild stroke and lack of elevated BP was associated with severe stroke. This could be explained by a protective effect of elevated BP in the acute phase of ischemic stroke, although the absence of association between elevated BP and favorable outcome argues against this hypothesis.