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The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6–24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation. MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6–24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220. Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2–6) in the endovascular treatment group and 6 (2–6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00–1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60–1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group. Our results show that the effectiveness of late-window (after 6–24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making. The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Interpretation Whereas highly cost‐effective and cost‐saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost‐effective in patients with extensive ischemic injury is uncertain.We conducted a model‐based cost‐effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7‐state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non‐health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost‐effective with a mean between‐group difference of 1.24 quality‐adjusted life years (QALYs), and a cost‐saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost‐effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base‐case results.EVT demonstrated cost‐effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background: The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective., Methods: A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses., Results: Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52 500 and $84 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52 500 threshold, and 79%, 91%, and 67% of simulations at the $84 000 threshold., Conclusions: Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52 500 threshold but possibly cost-effective at the $84 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT., Competing Interests: Drs Majoie and Roos declare to be shareholders of Nico-Lab, not involved in this study. Dr Majoie has reported grants from CardioVascular Research Netherlands (CVON)/Dutch Heart Foundation, European Commission, Stichting Toegepast Wetenschappelijk Instituut voor Neuromodulatie (TWIN) Foundation, Health Evaluation Netherlands, Boehringer Ingelheim, and Stryker (all paid to institution). Dr Coutinho is the cofounder and shareholder of TrianecT. He has received grants from Medtronic, Boehringer Ingelheim, Bayer, and AstraZeneca and is a consultant at Portola Pharmaceuticals, LLC. Dr van der Zee is a member of the supervisory board at Radiotherapeutisch Instituut Friesland. Dr Buskens is appointed by University Medical Center Groningen, has reported receiving funding from the Netherlands Heart Foundation and a Public-Private Partnership allowance from Health Holland, Care Research Netherlands and Medical Sciences (ZonMw), and Dutch Research Council (NWO) and serves as the ZonMw committee (vice) chairman. Also, Dr Buskens serves at ZuidOost Zorg and 113 Suicide prevention as a member of advisory board. Dr Uyttenboogaart has received research grants from ZonMw and Dutch Heart Foundation. The other authors report no conflicts.

Objective: To describe the incidence, risk factors, and prognostic relevance of intracranial haemorrhage (ICH) immediately after endovascular treatment (EVT) for ischaemic stroke in the anterior circulation., Methods: EVT records from 2010 to 2019 were screened. Included patients underwent DECT within 3h post-EVT. Virtual native reconstructions were evaluated for ICH according to the Heidelberg criteria and grouped into Heidelberg classes (HCs): [HC1] haemorrhagic infarction (HI)1, HI2 and parenchymal haematoma (PH)1; [HC2] PH2; [HC3] i.a. intraventricular and subarachnoid haemorrhage. If ICH corresponding to multiple HCs was observed, we assumed that the (largest) parenchymal ICH would have the greatest prognostic impact. Hence, a single HC was attributed by the following order of severity: HC2, HC1, HC3. The primary outcome was the modified Rankin Scale (mRS) at 90 days. The effect of asymptomatic ICH (aICH) and symptomatic ICH (sICH) of (1) HC1 or HC2 and (2) HC3 on patient outcomes was evaluated with multivariable regression after multiple imputation., Results: Out of 651 records, 498 patients were included. Eighty-one (16%) patients showed ICH on post-EVT DECT, of which 19 were classified as HC1 (21% symptomatic), 6 as HC2 (100% symptomatic), and 56 as HC3 (14% symptomatic). ICH development was mainly associated with unfavourable procedural characteristics. Both aICH and sICH of HC1 or HC2 were associated with the mRS (aICH: adjusted [a]cOR 4.92, 95%CI [1.48-16.35]; sICH: acOR 12.97, 95%CI [2.39-70.26]) and mortality (aICH: aOR 10.08, 95%CI [2.48-40.88]; sICH: aOR 9.92, 95%CI [1.48-66.31]). Likewise, sICH of HC3 was associated with the mRS and mortality (acOR 19.91, 95%CI [4.03-98.35], and aOR 13.23, 95%CI [2.27-77.18], respectively). aICH of HC3 was not significantly associated with the mRS or mortality (acOR 0.87, 95%CI [0.48-1.57], and cOR 0.84, 95%CI [0.32-2.20], respectively)., Conclusions: Immediate post-EVT ICH is a frequent finding. Except for aICH of HC3, any ICH is associated with poor long-term clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper. The authors declare the following financial or personal relationships that could be viewed as influencing the work reported in this paper: H.D. Boogaarts received consultation fees from Stryker Neurovascular (paid to the institution). W.H. van Zwam received consultation fees from Stryker, Nicolab and Cerenovus (paid to the institution), and is a DSMB member of the Philips’ We-Trust study, Anaconda's Solonda study, and In Extremis study (all funding paid to the institution). A.A. Postma received an institutional grant from Siemens Healthineers and Bayer Healthcare., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Model-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke., Methods: Included patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients., Results: 1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from €11 943 (mRS 1, no EVT) to €55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from €885 (mRS 0) to €23 215 (mRS 5), and from €1655 (mRS 0) to €22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point., Conclusions: The mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Endovascular treatment (EVT) is the preferred treatment option in eligible acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation. Several comorbidities have been identified that can affect clinical outcomes. Various studies have investigated the association between anemia and clinical outcome and found conflicting., Results: . The aim is to investigate the association between pre-EVT anemia and clinical outcomes at different time points post-EVT, primarily focusing on the National Institutes of Health Stroke Scale (NIHSS) at 24-48 hours., Methods: We prospectively included 560 AIS patients who received EVT in the Maastricht University Medical Center+. Hemoglobin levels (Hb; g/dL) were determined on admission. Hb levels were also categorized into two groups: anemia (male: Hb ≤12.9 g/dL; female: Hb ≤11.9 g/dL) and no anemia. Multiple imputation was used to handle missing data. Multivariable regression was used to investigate the association between anemia or Hb levels and clinical outcomes., Results: Anemia was present in 26% of the patients. Multivariable regression did not show a significant association between anemia or Hb levels and NIHSS at 24-48 hours (adjusted β [aβ]anemia: 1.44, 95% confidence interval [CI]: -0.47 to 3.36; aβHb: -0.37, 95% CI: -0.88 to 0.13). However, multivariable regression showed significant associations with modified Rankin Scale (adjusted common odds ratio [acOR]anemia: 1.66, 95% CI: 1.12 to 2.48; acORHb: 0.83, 95% CI: 0.75 to 0.93) and poor functional outcome at 90 days (adjusted OR [aOR]anemia: 2.09, 95% CI: 1.21 to 3.63; aORHb: 0.80, 95% CI: 0.69 to 0.92)., Conclusion: Anemia was not independently associated with early neurological deficit (NIHSS) post-AIS, suggesting it is more suitable as a general frailty marker.

Purpose: To determine the incidence and predictors of cerebral arterial air emboli (CAAE) on immediate post-endovascular treatment (EVT) dual-energy CT (DECT) in acute ischaemic stroke (AIS) patients, and describe their association with clinical outcomes., Methods: EVT records from 2010 to 2019 were screened. Exclusion criteria included intracerebral haemorrhage on post-EVT DECT. In the affected middle cerebral artery (MCA)-territory, circular and linear (length ≥ 1.5*width) CAAE were counted. Clinical data were collected from prospective records. The modified Rankin Scale (mRS) at 90 days was the primary outcome. Multivariable linear, logistic, and ordinal regression were used to analyse the effect of (1) linear CAAE and (2) isolated circular CAAE., Results: Out of 651 EVT-records, 402 patients were included. In 65 patients (16%), at least one linear CAAE was found in the affected MCA-territory. 17 patients (4%) showed isolated circular CAAE. Multivariable regression showed an association between both the presence and the number of linear CAAE and the mRS at 90 days (presence: adjusted (a)cOR 3.10, 95%CI 1.75-5.50; number: acOR 1.28, 95%CI 1.13-1.44), NIHSS at 24-48 h (presence: aβ 4.15, 95%CI 1.87-6.43; number: aβ 0.88, 95%CI 0.42-1.34), mortality at 90 days (presence: aOR 3.34, 95%CI 1.51-7.40; number: aOR 1.24, 95%CI 1.08-1.43) and stroke progression (presence: aOR 4.01, 95%CI 1.96-8.18; number: aOR 1.31, 95%CI 1.15-1.50). Isolated circular CAAE were not significantly associated with any outcome measure., Conclusion: CAAE were found frequently on post-EVT CT imaging. The presence and the number of linear CAAE, but not circular CAAE, are associated with unfavourable short- and long-term clinical outcomes., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated., Methods: In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p < 0.1 were selected for binary logistic regression analysis., Results: The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic drug-induced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (p = 0.002), a history of psychotic symptoms (p < 0.000), a history of psychiatric illness other than psychosis (p = 0.010), and concomitant phenytoin (PHT) usage (p = 0.044). Cotherapy with lamotrigine (LTG) was protective (p = 0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (p = 0.021) and history of psychotic symptoms (p = 0.018), as well as with female gender (p = 0.047) and intellectual disability (p = 0.043)., Conclusion: Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms., (Copyright © 2019 Elsevier Inc. All rights reserved.)