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"Simonsen, C. Z"
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General anesthesia during endovascular therapy for acute ischemic stroke: benefits beyond better reperfusion?
by
Valentin, Jan Brink
,
Bösel, Julian
,
Simonsen, Claus Z
in
Anestesi och intensivvård
,
Anesthesiology and Intensive Care
,
angiography
2022
BackgroundEndovascular therapy (EVT) is standard of care for stroke caused by large vessel occlusion. Whether EVT should be performed under general anesthesia (GA) or conscious sedation (CS) is controversial. While a meta-analysis of randomized trials showed better outcome for EVT under GA, observational studies suggested the opposite. A proposed advantage of GA is better reperfusion achieved via more successful handling of the immobile patient. The aim of this study was to investigate if the good outcome seen in patients treated under GA was mediated by better reperfusion.MethodsThe meta-analysis included 368 individual patients from three randomized controlled trials, of whom 185 patients were randomized to CS. A mediator analysis was performed to examine if the better outcome in the GA arm was driven by higher reperfusion rate.ResultsThe total effect showed a risk difference (RD) of 0.15 (95% CI 0.04 to 0.25), associating GA with a beneficial outcome. The direct effect of GA constituted a large portion, with an RD of 0.12 (95% CI 0.01 to 0.22), while only a small portion was mediated through the degree of reperfusion, with an RD of 0.03 (95% CI 0.02 to 0.04).ConclusionThe better outcome after EVT in the GA arm was mainly a direct effect—that is, an effect that was not explained by better reperfusion. We also found a better outcome in the GA arm when reperfusion was not achieved. Whether this is an effect of the stable condition and blood pressure under GA or a neuroprotective effect will need to be investigated in future research.
Journal Article
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
by
Ebinger, Martin
,
Roy, Pascal
,
Scheel, Enno
in
Acute Disease
,
Administration, Intravenous
,
Aged
2018
Among patients with stroke of unknown onset, thrombolytic treatment is withheld. In this randomized trial, such patients who had evidence of infarction on MRI but no FLAIR signal had a significantly better functional outcome with alteplase than with placebo.
Journal Article
MR-Based Statistical Atlas of the Göttingen Minipig Brain
2001
Thedomestic pig is increasingly being used as an experimental model for brain imaging studies with positron emission tomography (PET). The recording of radiotracer uptake by PET gives functional and physiological information, but with poor spatial resolution. To date, anatomical regions of interest in pig brain have been defined in MR images obtained for each individual animal, because of the lack of a standard stereotaxic coordinate system for the pig brain. In order to define a stereotaxic coordinate system, we coregistered T1-weighted MR images from 22 male Göttingen minipigs and obtained a statistically defined surface rendering of the average minipig brain in which stereotaxic zero is defined by the position of the pineal gland. The average brain is now used as a target for registration of dynamic PET data, so that time–activity curves can be extracted from standard volumes of interest. In order to define these volumes, MR images from each individual pig were manually segmented into a total of 34 brain structures, including cortical regions, white matter, caudate and putamen, ventricular system, and cerebellum. The mean volumes of these structures had variances in the range of 10–20%. The 34 brain volumes were transformed into the common coordinate system and then used to generate surface renderings with probabilistic threshold greater than 50%. This probabilistic threshold gave nearly quantitative recovery of the mean volumes in native space. The probabilistic volumes in stereotaxic space are now being used to extract time–radioactivity curves from dynamic PET recordings.
Journal Article
Correlation between Diffusion- and Perfusion-Weighted MRI and Neurological Deficit Measured by the Scandinavian Stroke Scale and Barthel Index in Hyperacute Subcortical Stroke (≤6 Hours)
2001
Objective: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. Material and Methods: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T 2 -weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). Results: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. Conclusions: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.
Journal Article
Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
by
Aarhus University Hospital
,
Nighoghossian, N
,
Ingwersen, T
in
59/57
,
631/378/116/1925
,
631/378/1689/534
2021
Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI(95%) [-8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI(95%) [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.
Journal Article
Influence of stroke infarct location on quality of life assessed in a multivariate lesion-symptom mapping study
2021
Stroke has a deleterious impact on quality of life. However, it is less well known if stroke lesions in different brain regions are associated with reduced quality of life (QoL). We therefore investigated this association by multivariate lesion-symptom mapping. We analyzed magnetic resonance imaging and clinical data from the WAKE-UP trial. European Quality of Life 5 Dimensions (EQ-5D) 3 level questionnaires were completed 90 days after stroke. Lesion symptom mapping was performed using a multivariate machine learning algorithm (support vector regression) based on stroke lesions 22-36 h after stroke. Brain regions with significant associations were explored in reference to white matter tracts. Of 503 randomized patients, 329 were included in the analysis (mean age 65.4 years, SD 11.5; median NIHSS = 6, IQR 4-9; median EQ-5D score 90 days after stroke 1, IQR 0-4, median lesion volume 3.3 ml, IQR 1.1-16.9 ml). After controlling for lesion volume, significant associations between lesions and EQ-5D score were detected for the right putamen, and internal capsules of both hemispheres. Multivariate lesion inference analysis revealed an association between injuries of the cortico-spinal tracts with worse self-reported quality of life 90 days after stroke in comparably small stroke lesions, extending previous reports of the association of striato-capsular lesions with worse functional outcome. Our findings are of value to identify patients at risk of impaired QoL after stroke.
Journal Article
Inter-Rater Agreement on Cincinnati Prehospital Stroke Scale (CPSS) and Prehospital Acute Stroke Severity Scale (PASS) Between EMS Providers, Neurology Residents and Neurology Consultants
by
Kirkegaard, Hans
,
Valentin, Jan Brink
,
Johnsen, Søren P
in
emergency medical service provider
,
neurologists
,
observer variation
2023
To examine the agreement between emergency medical service (EMS) providers, neurology residents and neurology consultants, using the Cincinnati Prehospital Stroke Scale (CPSS) and the Prehospital Acute Stroke Severity Scale (PASS).ObjectiveTo examine the agreement between emergency medical service (EMS) providers, neurology residents and neurology consultants, using the Cincinnati Prehospital Stroke Scale (CPSS) and the Prehospital Acute Stroke Severity Scale (PASS).Patients with stroke, transient ischemic attack (TIA) and stroke mimic were included upon primary stroke admission or during rehabilitation. Patients were included from June 2018 to September 2019. Video recordings were made of patients being assessed with CPSS and PASS. The recordings were later presented to the healthcare professionals. To determine relative and absolute interrater reliability in terms of inter-rater agreement (IRA), we used generalisability theory. Group-level agreement was determined against a gold standard and presented as an area under the curve (AUC). The gold standard was a consensus agreement between two neurology consultants.MethodsPatients with stroke, transient ischemic attack (TIA) and stroke mimic were included upon primary stroke admission or during rehabilitation. Patients were included from June 2018 to September 2019. Video recordings were made of patients being assessed with CPSS and PASS. The recordings were later presented to the healthcare professionals. To determine relative and absolute interrater reliability in terms of inter-rater agreement (IRA), we used generalisability theory. Group-level agreement was determined against a gold standard and presented as an area under the curve (AUC). The gold standard was a consensus agreement between two neurology consultants.A total of 120 patient recordings were assessed by 30 EMS providers, two neurology residents and two neurology consultants. Using the CPSS and the PASS, a total of 1,800 assessments were completed by EMS providers, 240 by neurology residents and 240 by neurology consultants. The overall relative and absolute IRA for all items combined from the CPSS and PASS score was 0.84 (95% CI 0.80; 0.87) and 0.81 (95% CI 0.77; 0.85), respectively. Using the CPSS, the agreement on a group-level resulted in AUCs of 0.83 (95% CI 0.78; 0.88) for the EMS providers and 0.86 (95% CI 0.82; 0.90) for the neurology residents when compared with the gold standard. Using the PASS, the AUC was 0.82 (95% CI 0.77; 0.87) for the EMS providers and 0.88 (95% CI 0.84; 0.93) for the neurology residents.ResultsA total of 120 patient recordings were assessed by 30 EMS providers, two neurology residents and two neurology consultants. Using the CPSS and the PASS, a total of 1,800 assessments were completed by EMS providers, 240 by neurology residents and 240 by neurology consultants. The overall relative and absolute IRA for all items combined from the CPSS and PASS score was 0.84 (95% CI 0.80; 0.87) and 0.81 (95% CI 0.77; 0.85), respectively. Using the CPSS, the agreement on a group-level resulted in AUCs of 0.83 (95% CI 0.78; 0.88) for the EMS providers and 0.86 (95% CI 0.82; 0.90) for the neurology residents when compared with the gold standard. Using the PASS, the AUC was 0.82 (95% CI 0.77; 0.87) for the EMS providers and 0.88 (95% CI 0.84; 0.93) for the neurology residents.The high relative and absolute inter-rater agreement underpins a high robustness/generalisability of the two scales. A high agreement exists across individual raters and different groups of healthcare professionals supporting widespread applicability of the stroke scales.ConclusionThe high relative and absolute inter-rater agreement underpins a high robustness/generalisability of the two scales. A high agreement exists across individual raters and different groups of healthcare professionals supporting widespread applicability of the stroke scales.
Journal Article
Select wisely: the ethical challenge of defining large core with perfusion in the early time window
by
Bendszus, Martin
,
Liebeskind, David
,
Leslie-Mazwi, Thabele M
in
Brain Ischemia
,
Commentary
,
CT perfusion
2021
Because the pivotal trials show unequivocally that patients with ASPECTS 6–10 and ELVO benefit from endovascular treatment in the 0–6-hour time window, we believe that this subgroup in SELECT 2 withholds proven class I treatment from eligible patients, raising concern for patient harm. From the 2015 trials there is a wealth of level I evidence showing that NCCT ASPECTS 6–10 patients benefit from thrombectomy in the early window and also that the effect size for this group is massive, with a number needed to treat of approximately 3.23 It is important to underscore that this group includes a substantial number of patients with CTP-estimated core volume ≥50 mL.24 In subgroup analysis of 175 subjects from MR CLEAN who underwent baseline CTP, these subjects had good NCCT ASPECTS (median 9 (IQR 7–10)), but a surprisingly high number (42%) were deemed unfavorable candidates by CTP based on the EXTEND IA mismatch criteria (mismatch defined as core volume <70 mL and mismatch ≥10 mL and 20% larger than core).24 Critically, their results showed a strong treatment benefit in both the favorable and unfavorable CTP groups. Alternatively, how should one interpret a trial result if both subgroups show a signal of benefit, but neither are statistically significant? Because data from one group cannot inform the results of the other, one is left with incomplete answers. [...]if the trials decide to continue, will the knowledge of the potential benefit in SELECT 2 undermine the equipoise of the investigators?
Journal Article
Intraventricular Lavage vs External Ventricular Drainage for Intraventricular Hemorrhage: A Randomized Clinical Trial
by
Claus Ziegler Simonsen
,
Anders Rosendal Korshøj
,
Naveed Ur Rehman
in
Catheters
,
Clinical trials
,
Hemorrhage
2023
Importance Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023. Interventions Participants were randomized to receive either intraventricular lavage or standard drainage. Main Outcomes and Measures The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency. Results A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81;P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1;P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2];P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control (P < .001). Conclusions and Relevance This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety. Trial Registration ClinicalTrials.gov Identifier:NCT05204849
Journal Article