2B, 2C, or 3: What Should Be the Angiographic Target for Endovascular Treatment in Ischemic Stroke?

Background and Purpose - A score of ≥2B on the modified Thrombolysis in Cerebral Infarction scale is generally regarded as successful reperfusion after endovascular treatment for ischemic stroke. The extended Thrombolysis in Cerebral Infarction (eTICI) includes a 2C grade, which indicates near-perfect reperfusion. We investigated how well the respective eTICI scores of 2B, 2C, and 3 correlate with clinical outcome after endovascular treatment. Methods - We used data from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, nationwide registry of endovascular treatment in the Netherlands. We included patients with a proximal intracranial occlusion of the anterior circulation for whom final antero-posterior and lateral digital subtraction angiography imaging was available. Our primary outcome was the distribution on the modified Rankin Scale at 90 days per eTICI grade. We performed (ordinal) logistic regression analyses, using eTICI 2B as reference group, and adjusted for potential confounders. Results - In total, 2807/3637 (77%) patients met the inclusion criteria. Of these, 17% achieved reperfusion grade eTICI 0 to 1, 14% eTICI 2A, 25% eTICI 2B, 12% eTICI 2C, and 32% eTICI 3. Groups differed in terms of age (P<0.001) and occlusion location (P<0.01). Procedure times decreased with increasing reperfusion grades. We found a positive association between reperfusion grade and functional outcome, which continued to increase after eTICI 2B (adjusted common odds ratio, 1.22 [95% CI, 0.96-1.57] for eTICI 2C versus 2B; adjusted common odds ratio, 1.33 [95% CI, 1.09-1.62] for eTICI 3 versus 2B). Conclusions - Our results indicate a continuous relationship between reperfusion grade and functional outcome, with eTICI 3 leading to the best outcomes. Although this implies that interventionists should aim for the highest possible reperfusion grade, further research on the optimal strategy is necessary

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Periprocedural Intravenous Heparin during Endovascular Treatment for Ischemic Stroke: Results from the MR CLEAN Registry

Background and Purpose-Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods-Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results-One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio,

qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

Background: The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. Aims: We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. Methods: We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0–2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. Results: In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58–88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. Conclusion: qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score

Eine Einführung in die Inverted-Classroom-Methode in der medizinischen Ausbildung

Zielgruppe: Der Workshop richtet sich an alle Personen, die sich für die Inverted Classroom Methode(ICM) interessieren und diese ggf. für eigene Lehrprojekte anwenden möchten Lernziele: Ziel des Workshops ist es, die Teilnehmer zu befähigen, die ICM auf die eigene Lehre anzuwenden. Inhalt: Der Workshop gibt eine Einführung in die ICM, skizziert ihre Vor- und Nachteile unter Einbeziehung aktueller Forschungsergebnisse und vermittelt praktische Fertigkeiten, um eigene Konzept für die Lehre entwickeln zu können. Dabei werden zusätzlich Themen wie Video-und Screencasterstellung, Open Educational Resources und Urheberrechte skizziert. Ablauf: Der Workshop selbst ist nach der ICM konzipiert. Das bedeutet, dass sich die Teilnehmer bereits im Vorfeld in einer Online-Phase das notwendige Faktenwissen aneignen, um in der Präsenzphase das erlernte Wissen in Kleingruppen anzuwenden und ICM-Konzepte für die eigene Lehre zu entwickeln. Diese Konzepte werden am Ende in der Gruppe vorgestellt und diskutier

Thrombus Migration Paradox in Patients With Acute Ischemic Stroke

Background and Purpose- The location of the thrombus as observed on first digital subtraction angiography during endovascular treatment may differ from the initial observation on initial noninvasive imaging. We studied the incidence of thrombus dynamics, its impact on patient outcomes, and its association with intravenous thrombolytics. Methods- We included patients from the MR CLEAN registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke) with an initial target occlusion on computed tomography angiography located in the intracranial internal carotid artery, M1, or M2. The conventional angiography target occlusion was defined during endovascular treatment. Thrombus dynamics were classified as growth, stability, migration, and resolution. The primary outcome was functional outcome at 90 days (modified Rankin Scale). The secondary outcomes were successful and complete reperfusion (extended treatment in cerebral infarction scores of 2b-3 and 3, respectively). Results- The analysis included 1349 patients. Thrombus migration occurred in 302 (22%) patients, thrombus growth in 87 (6%), and thrombus resolution in 39 (3%). Intravenous treatment with alteplase was associated with more thrombus migration (adjusted odds ratio, 2.01; CI, 1.29-3.11) and thrombus resolution (adjusted odds ratio, 1.85; CI, 1.22-2.80). Thrombus migration was associated with a lower chance of complete reperfusion (adjusted odds ratio, 0.57; CI, 0.42-0.78) and successful reperfusion (adjusted odds ratio, 0.74; CI, 0.55-0.99). In the subgroup of patients with M1 initial target occlusion, thrombus migration was associated with better functional outcome (adjusted common odds ratio, 1.49; CI, 1.02-2.17), and there was a trend towards better functional outcome in patients with thrombus resolution (adjusted common odds ratio, 2.23; CI, 0.93-5.37). Conclusions- In patients with acute ischemic stroke, thrombus location regularly changes between computed tomography angiography and digital subtraction angiography. Administration of intravenous alteplase increases the chance of thrombus migration and resolution. Thrombus migration is associated with better functional outcome but reduces the rate of complete reperfusion

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

Background: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. Methods: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. Results: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. Conclusion: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs

Blood Pressure During Endovascular Treatment Under Conscious Sedation or Local Anesthesia

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group

Thrombectomy in posterior circulation stroke through persistent primitive trigeminal artery: A case report

We describe a case of intra-arterial treatment (IAT) of acute posterior circulation occlusion in a patient with a persistent primitive trigeminal artery (PPTA). The pati