Monitoring following acute stroke should be improved. / Overvåkning etter akutt hjerneslag bør bli bedre.

Many serious complications following acute stroke can be prevented and treated. This requires close and systematic monitoring following stroke.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome.

BACKGROUND: We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). METHODS AND RESULTS: This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8-22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1-1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. CONCLUSIONS: IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Leukoaraiosis is associated with short- and long-term mortality in patients with intracerebral hemorrhage.

BACKGROUND: There are few recent European studies of mortality after intracerebral hemorrhage (ICH), particularly long-term follow-up studies. No previous European studies have included information on leukoaraiosis. METHODS: We studied all consecutive patients hospitalized with a first-ever intracerebral hemorrhage between 2005 and 2009 in a well-defined area and assessed the prognostic value of various baseline clinical and radiologic factors. Leukoaraiosis was scored on the baseline computed tomographic (CT) scan as described by van Swieten et al, with an overall score from 0 to 4. RESULTS: One hundred thirty-four patients were followed up for a median of 4.7 years (interquartile range 2.5-6.6). Overall mortality was 23% at 2 days, 30% at 7 days, 37% at 30 days, 46% at 1 year, and 53% at 2 years. Factors independently associated with increased 30-day mortality were warfarin use, leukoaraiosis score, intraventricular hemorrhage, and Glasgow Coma Scale (GCS) score. Factors independently associated with long-term mortality in the 85 patients who survived the first 30 days were leukoaraiosis score, coronary heart disease, and initial GCS score. Recurrent ICH occurred in 4.5% and was significantly more frequent after lobar ICH than after ICH in other locations (11.1% v 0%; P = .025). CONCLUSIONS: In unselected patients in Southern Norway with first-ever ICH, severe leukoaraiosis is independently associated with both 30-day and long-term mortality in 30-day survivors. Warfarin is independently associated with 30-day mortality and coronary heart disease with long-term mortality in 30-day survivors. Recurrent ICH is more frequent after lobar ICH than after ICH in other locations.

Virtual reality simulation training in stroke thrombectomy centers with limited patient volume-Simulator performance and patient outcome.

BACKGROUND: Virtual reality simulation training may improve the technical skills of interventional radiologists when establishing endovascular thrombectomy at limited-volume stroke centers. The aim of this study was to investigate whether the technical thrombectomy performance of interventional radiologists improved after a defined virtual reality simulator training period. As part of the quality surveillance of clinical practice, we also assessed patient outcomes and thrombectomy quality indicators at the participating centers. METHODS: Interventional radiologists and radiology residents from three thrombectomy-capable stroke centers participated in a five months thrombectomy skill-training curriculum on a virtual reality simulator. The simulator automatically registered procedure time, the number of predefined steps that were correctly executed, handling errors, contrast volume, fluoroscopy time, and radiation dose exposure. The design was a before-after study. Two simulated thrombectomy cases were used as pretest and posttest cases, while seven other cases were used for training. Utilizing the Norwegian Stroke Register, we investigated clinical results in thrombectomy during the study period. RESULTS: Nineteen interventional radiologists and radiology residents participated in the study. The improvement between pretest and posttest cases was statistically significant for all outcome measures in both simulated cases, except for the contrast volume used in one case. Clinical patient outcomes in all three centers were well within the recommendations from multi-society consensus guidelines. CONCLUSION: Performance on the virtual reality simulator improved after training. Virtual reality simulation may improve the learning curve for interventional radiologists in limited-volume thrombectomy centers. No correlation alleged, the clinical data indicates that the centers studied performed thrombectomy in accordance with guideline-recommended standards.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Intracerebral hemorrhage in southern Norway--a hospital-based incidence study.

BACKGROUND/AIMS: Newer Scandinavian data on intracerebral hemorrhage (ICH) are scarce. We aimed at providing updated community-based data on the incidence, characteristics and outcome of ICH leading to hospitalization in the southernmost region in Norway. METHODS: We analyzed data from all consecutive patients hospitalized with a first-ever ICH in the five-year period 2005-2009 in a well-defined area served by one single hospital. Cases were found by computerized search in a register covering all in- and outpatients. RESULTS: Adjusted to the standard European population the annual incidence rate per 100,000 was 16.9 for men, 8.8 for women (p < 0.001) and 12.5 for both sexes. The incidence rates rose continuously with increasing age through all age groups in both sexes. The proportion with warfarin-associated ICH was 26.9%. The overall 30-day case fatality rate was 36.6%. The hematoma location was lobar in 36.6%, deep cerebral in 45.5%, cerebellar in 9.7%, and brain stem in 8.2%. CONCLUSIONS: The incidence of ICH in the southernmost region in Norway is in the midrange in Europe and lower than in previous Scandinavian studies. Men are at higher risk than women. The proportion with warfarin-associated ICH is higher than previously reported from Scandinavia.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Introduction: Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. Patients and methods: We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Results: Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Discussion and conclusions: Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST).

BACKGROUND: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. OBJECTIVE: To publish the detailed statistical analysis plan for TWIST prior to unblinding. METHODS: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting. DISCUSSION: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial.

BACKGROUND: Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT. METHODS/DESIGN: TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n = 300) versus standard care (n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months. DISCUSSION: TWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.