The relationship of functional outcome after mechanical thrombectomy and serum glucose is partially mediated by edema formation

IntroductionHigh blood glucose was shown to be associated with worse clinical outcome and increased edema formation in patient with acute stroke undergoing mechanical thrombectomy.1 A better understanding of the pathophysiological pathways and a quantification of their effects might support targeted therapeutic approaches.Aim of the StudyTo quantify the amount of outcome deterioration explained by edema formation due to high blood glucose.Methods124 patients with acute ischemic stroke who underwent mechanical thrombectomy were included. Mediation analysis was performed to quantify the amount of outcome deterioration (probability for mRS>2) explained by edema formation in patients with high blood glucose. In addition, the moderating effects of good and poor collaterals were investigated.ResultsProbability for poor outcome increased with increasing blood glucose levels (OR 1.23/10 mg/dl), edema formation (OR 1.13/% net water uptake) and poor collaterals (OR 1.64). Edema formation was also associated with higher blood glucose levels (regression coefficient 0.033). An increase of blood glucose levels from 100mg/dl to 200mg/dl resulted in a 47 percentage-points decrease of the probability of good outcome in patients with good collaterals and a 26 percentage points decrease in patients with poor collaterals. Edema formation explained 15% of the outcome deterioration caused by higher blood glucose levels.ConclusionEdema formation explains 15% of the total adverse effects of high blood glucose levels. Major pathways might include other direct effects of high blood glucose, such as altered vessel wall and thrombus characteristics and higher thrombogenicity of the cerebral blood flow.ReferencesThorén, M., et al. “Predictors for Cerebral Edema in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.” Stroke 2017;48(9): 2464–2471.Do you have any conflict of interest to declare?: YesHelge Kniep is a consultant for Eppdata.Jens Fiehler received research support from: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Route92, Stryker. He is consultant for: Acandis, Bayer, Cerenovus, Covidien, Medtronic, Microvention, Penumbra, Phenox, Stryker and stock holder of Tegus Medical.

How much of the improvement in functional outcome after successful recanalization is explained by follow-up infarct volume reduction?

IntroductionMechanical thrombectomy (MT) has been shown to improve functional outcome in patients with anterior circulation stroke. However, previous works suggest only limited explanatory effect of infarct volume reduction on outcome in patients undergoing MT vs. standard medical care1.Aim of the studyThe amount of improvement of functional outcome explained by follow-up infarct volume reduction after successful recanalization has not been investigated in detail. Results might allow quantification of pathophysiological effects and could improve the understanding of the value of follow-up infarct volume as imaging endpoint in clinical trials.MethodsAll patients from our institution enrolled in the German Stroke Registry from 05/2015 to 12/2019 with anterior circulation stroke, availability of the relevant clinical data and follow-up CT (12h-2 weeks) were analyzed. A mediation analysis was conducted to investigate the effect of successful recanalization (Tici≥2b) on good functional outcome (90d mRS≤2) with mediation through follow-up infarct volume.Results429 patients were included. Multivariate regression confirms significant association of successful recanalization with lower follow-up infarct volume and better functional outcome. Results of the mediation analysis suggest a 23 percentage points (pp) increase of probability of good function outcome (95%CI: 16pp-29pp) in patients with successful recanalization. 57% (95%CI: 38%-79%) of the treatment effect was explained by follow-up volume reduction.Conclusions57% of the improvement of functional outcome after successful recanalization is explained by follow-up infarct volume reduction. Results reflect established pathophysiological assumptions and confirm the value of infarct volume as imaging endpoint in clinical trials.ReferencesBoers AMM, Jansen IGH, Brown S, et al. Mediation of the relationship between endovascular therapy and functional outcome by follow-up infarct volume in patients with acute ischemic stroke. Jama Neurology 2019;76:194–202. DOI: 10.1001/Jamaneurol.2018.3661Do you have any conflict of interest to declare?: YesHelge Kniep, Fabian Flottmann and Friederike Austein are consultants for Eppdata.Milani Deb-Chatterji has received research grants from the Werner Otto Stiftung.Gabriel Broocks received grants from Balt USA, LLC.Götz Thomalla received fees as consultant from Acandis, Bayer, and Portola, and fees as lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer-Ingelheim, BristolMyersSquibb, Daiichii Sankyo, Portola, and Stryker.Jens Fiehler received research support from: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Route92, Stryker. He is consultant for: Acandis, Bayer, Cerenovus, Covidien, Medtronic, Microvention, Penumbra, Phenox, Stryker and stock holder of Tegus Medical.

Thrombectomy for medium vessel occlusions: treatment effect of successful recanalization on long term functional outcome

IntroductionTreatment effects of successful recanalization after mechanical thrombectomy (MT) have been evaluated for acute ischemic strokes with large vessel occlusion. However, for medium-vessel occlusions (MeVO) treatment effects of successful recanalization have not been investigated in detail.Aim of the studyTo quantify treatment effects of different degrees of recanalization after MT in MeVO on long term function outcome.MethodsAll patients enrolled in the German Stroke Registry from 05/2015 to 12/2019 with MeVO of the middle cerebral artery and availability of the relevant data points were included. The treatment effect of different degrees of recanalization (TICI scores) was analyzed using established binarized outcome metrics (good outcome: 90d mRS≤2) and linearized outcome metrics defined as the mRS increase pre-stroke to 90d. Treatment effects were assessed using double robust inverse-probability-weighted regression-adjustment estimators for multivalued treatments.Results597 patients fulfilled the inclusion criteria. 97 (16%) patients had TICI<2b with good outcome in 19%. 194 (33%) patients had TICI 2b and 296 (50%) had TICI 3. For both cohorts, percentage of good outcome was 55%. Covariate-controlled treatment effect estimation suggests that TICI 2b recanalization increases probability of good long-term functional outcome from 27% to 58% (31 pp). Pre-stroke to 90d mRS increase was reduced by 1.0 mRS points. Full recanalization with TICI 3 did not further increase probability of good outcome and did not further reduce stroke-related mRS increase.ConclusionTICI 2b recanalization in MeVO increased probability of good outcome from 27% to 58%, TICI 3 recanalization did not further improve prognosis.Do you have any conflict of interest to declare?: YesConflict of Interest StatementHelge Kniep and Fabian Flottmann are consultants for Eppdata.Milani Deb-Chatterji has received research grants from the Werner Otto Stiftung.Götz Thomalla received fees as consultant from Acandis, Bayer, and Portola, and fees as lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer-Ingelheim, BristolMyersSquibb, Daiichii Sankyo, Portola, and Stryker.Jens Fiehler received research support from: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB), Medtronic, Microvention, Route92, Stryker. He is consultant for: Acandis, Bayer, Cerenovus, Covidien, Medtronic, Microvention, Penumbra, Phenox, Stryker and stock holder of Tegus Medical.