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 wakeup 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 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

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.publishedVersio

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

publishedVersio

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 lschaemic 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 (CON-SORT) 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.Peer reviewe

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 lschaemic 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 (CON-SORT) 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.Peer reviewe

Intracerebral Hemorrhage In Southern Norway. A study of incidence and outcome

Aims: We aimed to assess the incidence and baseline characteristics of first ever intracerebral hemorrhage (ICH) in Southern Norway leading to hospitalization, mortality rates after ICH and factors associated with 30-day mortality and long term mortality. We further aimed to assess clinical functioning including cognition in long term survivors and associations between baseline factors and 1) functional dependency and 2) cognitive impairment. We also aimed to assess the rate of recurrent ICH and late seizures. Materials and methods: All consecutive patients hospitalized with a first-ever ICH in the period 2005-2009 in a well-defined area were identified. Risk factors, clinical-, and radiological data were recorded in a stroke register from September 2007 and retrieved from patient files in cases prior to that. In Paper I we calculated the crude incidence and the incidence adjusted to the standard European population. In paper II death registered up to December 31.2011 in the National Population Register was recorded and causes of death were obtained from Statistics Norway and patient files. The prognostic value of various baseline clinical and radiologic factors for 30-day and long term mortality was assessed. Information on recurrent ICH was obtained by review of patient files. In Paper III we did an extensive in person follow up of all long term survivors between August and November 2011. This included the National Institute of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and the Montreal Cognitive Assessment (MoCA). Information on late seizures was obtained through the in person follow up and by review of patient files. Results: Incidence (Paper I): We identified 134 patients, 74 (55%) men and 60 (45%) women with first ever ICH. The crude annual incidence rate per 100.000 per year was 19.6 for men, 15.7 for women and 17.6 for both sexes. Adjusted to the standard European population it was 16.9 for men, 8.8 for women (p<0.001) and 12.5 for both sexes. The overall age adjusted rate ratio men/women was 1.78 (p=0.001). Hematoma location was lobar in 36.6%, deep cerebral in 45.5%, cerebellar in 9.7%, and brain stem in 8.2%. Intraventricular hemorrhage occurred in 37%. The proportion with oral anticoagulant treatment associated ICH (OAT-ICH) was 26.9%. Mortality (Paper I and II): Overall mortality at 2 days was 23%, at 7 days 30%, at 30 days 36.6%, at 1 year 46 % and at 2 years 53%. Factors independently associated with 30-day mortality were warfarin, Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, and leukoaraiosis (LA) score. Factors independently associated with long term mortality in 30-day survivors were coronary heart disease (CHD), GCS score, and LA score. Median follow up time was 4.7 years. Recurrent ICH (Paper II): Recurrent ICH was seen in 4 of 36 patients (11.1%) discharged alive after a lobar index ICH versus 0 of 52 (0%) after index ICH in other locations (p=0.025). Clinical functioning in long term survivors (Paper III): Of 51 patients alive 50 (24 men and 26 women) had an in person follow up after a median of 3.8 years. Men were younger than women (70.4 versus 78.7 years, p=0.019). Forty one (82%) lived in their private homes and 9 (18%) in nursing homes, 34 (68%) were independent (mRS 0-2) and 16 (32%) were dependent (mRS 3-5). Factors independently associated with dependency were female sex and LA score. The proportion with cognitive impairment (MoCA≤23) was 61.4%. Factors independently associated with cognitive impairment were age and lobar ICH location. Late seizures (not published): Late seizures occurred in 5 of 50 (10%) long term survivors; 5 of 19 (26%) with lobar ICH versus 0 of 31 (0%) with ICH in other locations (p=0.005). Patients with late seizures had larger median ICH volumes than patients without seizures, 39 ml (IQR 23.5- 58.5) versus 7 ml (IQR 2.5-16.5), p=0.004. Conclusions: The incidence of first ever ICH in Southern Norway is in the mid range in Europe and lower than in the only prior Norwegian incidence study. Men are at higher risk than women. The proportion with OAT-ICH is higher than in most reports reflecting a well implemented use of warfarin in atrial fibrillation in the elderly (Paper I). LA is independently associated with both 30-day mortality 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 (Paper II). The majority of long term survivors live in their private homes. Two thirds are functionally independent. Dependency is associated with LA and female sex. Cognitive impairment is common and associated with lobar location of ICH (Paper III). Late seizures were associated with lobar index ICH and larger ICH volumes (not published)

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.Peer reviewe

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

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.</p

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