Prognostic value of recanalization attempts in endovascular therapy for M2 segment middle cerebral artery occlusions.

BACKGROUND: There is growing evidence suggesting efficacy of endovascular therapy for M2 occlusions of the middle cerebral artery. More than one recanalization attempt is often required to achieve successful reperfusion in M2 occlusions, associated with general concerns about the safety of multiple maneuvers in these medium vessel occlusions. AIM: The aim of this study was to investigate the association between the number of recanalization attempts and functional outcomes in M2 occlusions in comparison with large vessel occlusions (LVO). METHODS: Retrospective multicenter cohort study of patients who underwent endovascular therapy for primary M2 occlusions. Patients were enrolled in the German Stroke Registry at 1 of 25 comprehensive stroke centers between 2015 and 2021. The study cohort was subdivided into patients with unsuccessful reperfusion (mTICI 0-2a) and successful reperfusion (mTICI 2b-3) at first, second, third, fourth, or ⩾fifth recanalization attempt. Primary outcome was 90-day functional independence defined as modified Rankin Scale score of 0-2. Safety outcome was the occurrence of symptomatic intracranial hemorrhage. Internal carotid artery or M1 occlusions were defined as LVO and served as comparison group. RESULTS: A total of 1078 patients with M2 occlusion were included. Successful reperfusion was observed in 87.1% and 90-day functional independence in 51.9%. The rate of functional independence decreased gradually with increasing number of recanalization attempts (p < 0.001). In both M2 occlusions and LVO, successful reperfusion within three attempts was associated with greater odds of functional independence, while success at ⩾fourth attempt was not. Patients with ⩾4 attempts exhibited higher rates of symptomatic intracranial hemorrhage in M2 occlusions (6.5% vs 2.7%, p = 0.02) and LVO (7.2% vs 3.5%, p < 0.001). CONCLUSION: This study suggests a clinical benefit of successful reperfusion within three recanalization attempts in endovascular therapy for M2 occlusions, which was similar in LVO. Our findings reduce concerns about the risk-benefit ratio of multiple attempts in M2 medium vessel occlusions. DATA ACCESS STATEMENT: The data that support the findings of this study are available on reasonable request after approval of the German Stroke Registry (GSR) steering committee. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03356392.

Predictors of functional outcome after thrombectomy for M2 occlusions: a large scale experience from clinical practice.

Mechanical thrombectomy (MT) for acute ischemic stroke with medium vessel occlusions is still a matter of debate. We sought to identify factors associated with clinical outcome after MT for M2-occlusions based on data from the German Stroke Registry-Endovascular Treatment (GSR-ET). All patients prospectively enrolled in the GSR-ET from 05/2015 to 12/2021 were analyzed (NCT03356392). Inclusion criteria were primary M2-occlusions and availability of relevant clinical data. Factors associated with excellent/good outcome (modified Rankin scale mRS 0-1/0-2), poor outcome/death (mRS 5-6) and mRS-increase pre-stroke to day 90 were determined in multivariable logistic regression. 1348 patients were included. 1128(84%) had successful recanalization, 595(44%) achieved good outcome, 402 (30%) had poor outcome. Successful recanalization (odds ratio [OR] 4.27 [95% confidence interval 3.12-5.91], p < 0.001), higher Alberta stroke program early CT score (OR 1.25 [1.18-1.32], p < 0.001) and i.v. thrombolysis (OR 1.28 [1.07-1.54], p < 0.01) increased probability of good outcome, while age (OR 0.95 [0.94-0.95], p < 0.001), higher pre-stroke-mRS (OR 0.36 [0.31-0.40], p < 0.001), higher baseline NIHSS (OR 0.89 [0.88-0.91], p < 0.001), diabetes (OR 0.52 [0.42-0.64], p < 0.001), higher number of passes (OR 0.75 [0.70-0.80], p < 0.001) and intracranial hemorrhage (OR 0.26 [0.14-0.46], p < 0.001) decreased the probability of good outcome. Additional predictors of mRS-increase pre-stroke to 90d were dissections, perforations (OR 1.59 [1.11-2.29], p < 0.05) and clot migration, embolization (OR 1.67 [1.21-2.30], p < 0.01). Corresponding to large-vessel-occlusions, younger age, low pre-stroke-mRS, low severity of acute clinical disability, i.v. thrombolysis and successful recanalization were associated with good outcome while diabetes and higher number of passes decreased probability of good outcome after MT in M2 occlusions. Treatment related complications increased probability of mRS increase pre-stroke to 90d.

Comparison of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 reperfusion in endovascular therapy for large ischemic anterior circulation strokes.

BACKGROUND: Landmark thrombectomy trials have provided evidence that selected patients with large ischemic stroke benefit from successful endovascular therapy, commonly defined as incomplete (modified Thrombolysis In Cerebral Infarction (mTICI) 2b) or complete reperfusion (mTICI 3). We aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in large ischemic strokes. METHODS: This retrospective multicenter cohort study was conducted to compare mTICI 2b versus mTICI 3 in large ischemic strokes in the anterior circulation. Patients enrolled in the German Stroke Registry between 2015-2021 were analyzed. Large ischemic stroke was defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. Patients were matched by final mTICI grade using propensity score matching. Primary outcome was the 90-day modified Rankin Scale (mRS) score. RESULTS: After matching, 226 patients were included. Baseline and imaging characteristics were balanced between mTICI 2b and mTICI 3 patients. There was no shift on the mRS favoring mTICI 3 compared with mTICI 2b in large ischemic strokes (adjusted common odds ratio (acOR) 1.12, 95% confidence interval (95% CI) 0.64 to 1.94, P=0.70). The rate of symptomatic intracranial hemorrhage was higher in mTICI 2b than in mTICI 3 patients (12.6% vs 4.5%, P=0.03). Mortality at 90 days did not differ between mTICI 3 and mTICI 2b (33.6% vs 37.2%; adjusted OR 0.69, 95% CI 0.33 to 1.45, P=0.33). CONCLUSIONS: In endovascular therapy for large ischemic strokes, mTICI 3 was not associated with better 90-day functional outcomes compared with mTICI 2b. This study suggests that mTICI 2b might be warranted as the final angiographic result, questioning the benefit/risk ratio of additional maneuvers to seek for mTICI 3 in large ischemic strokes. TRIAL REGISTRATION NUMBER: NCT03356392.

Evaluation of intracranial stenting in a simulated training and assessment environment for neuroendovascular procedures.

Purpose: Given the inherent complexity of neurointerventional procedures and the associated risks of ionizing radiation exposure, it is crucial to prioritize ongoing training and improve safety protocols. The aim of this study is to assess a training and evaluation in-vitro environment using a vascular model of M1 stenosis, within a clinical angiography suite, without relying on animal models or X-ray radiation. Materials and methods: Using a transparent model replicating M1 stenosis, we conducted intracranial stenting procedures with four different setups (Gateway & Wingspan, Gateway & Enterprise, Neurospeed & Acclino, and Pharos Vitesse). A video camera was integrated with the angiography system's monitor for real-time visualization, while a foot switch was employed to simulate live fluoroscopy. Three neuroradiologists with varying levels of expertise performed each procedure for three times. The total duration of fluoroscopy as well as the time from passing the stenosis with the wire to completion of the procedure were recorded using a dedicated software designed for this experimental setup. Results: Compared to the Gateway & Wingspan procedure, the total fluoroscopy time reduced significantly with the Gateway & Enterprise, Neurospeed & Acclino, and Pharos Vitesse procedures by 51.56 s, 111.33 s, and 144.89 s, respectively (p < 0.001). Additionally, physicians with under 2 years and over 5 years of experience reduced FT by 62.83 s and 106.42 s, respectively, (p < 0.001), compared to a novice physician. Similar trends were noted for the time of wire distal to stenosis, with significant reductions for Neurospeed & Acclino and Pharos Vitesse compared to both Gateway & Wingspan as well as Gateway & Enterprise (all p < 0.001). Conclusion: Procedures requiring wire exchange maneuvers exhibited nearly twice the fluoroscopy time in comparison to balloon-mounted stenting or stent-placement via PTA balloon catheters. The more experienced neuroradiologist demonstrated significantly quicker performance in line with expectations in a real-life clinical setting, when compared to the less experienced interventionalist. This in-vitro setup allowed the evaluation of alternative technical approaches and differences in experience of operators without the use of animal models or X-ray. The setup combines advantages of simulators and silicone vessel models in a realistic working environment.

First experience with Walrus balloon guide catheter in a whole-body flow model.

PURPOSE: Flow arrest using a balloon guide catheter (BGC) in mechanical thrombectomy (MT) due to large vessel occlusion has been associated with better outcomes. Known limitations of currently commercially available BGCs are incompatibility with large bore aspiration catheters (AC) and lack of distal flexibility. Walrus presents variable stiffness and compatibility with large bore AC. The goal of this study is to describe the first experience with Walrus in a realistic stroke simulation model. METHODS: A full-length modular vascular model under physiological conditions was used. 8F+-Walrus inner-diameter (ID) 0.087in 95 cm combined with 6F-Sofia AC ID 0.070in 131 cm and an 8F-Flowgate2 BGC ID 0.084in 95 cm with a 5F-Sofia AC ID 0.055in 125 cm were used to perform aspiration MT. User surveys, access to target and occlusion site, technique, time of delivery, anatomical change, and catheter kick-back were assessed. RESULTS: Seven neuroradiologists with average of 10 years-experience in MT performed primary aspiration using the above-mentioned combinations in three different anatomies (N = 41). All operators would likely (29%) or very likely (71%) use again Walrus in combination with large bore AC and the majority (86%) found its navigability easier than with other BGCs. Time to reach final BGC position and catheter kick-back did not differ significantly among anatomies or catheter combinations (p > 0.05). However, Walrus was more likely to reach ICA petrous segment (p < 0.05) and intracranial occlusion with AC (p < 0.01). CONCLUSION: The Walrus combined with large bore AC presented significantly better distal access and navigability for primary aspiration in an in vitro stroke model.

Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke.

BACKGROUND: Recently, 3 randomized controlled trials provided high-level evidence that patients with large ischemic stroke achieved better functional outcomes after endovascular therapy than with medical care alone. We aimed to investigate whether the clinical benefit of endovascular therapy is associated with the number of recanalization attempts in extensive baseline infarction. METHODS: This retrospective multicenter study enrolled patients from the German Stroke Registry who underwent endovascular therapy for anterior circulation large vessel occlusion between 2015 and 2021. Large ischemic stroke was defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5. The study cohort was divided into patients with unsuccessful reperfusion (Thrombolysis in Cerebral Infarction score, 0-2a) and successful reperfusion (Thrombolysis in Cerebral Infarction score, 2b/3) at attempts 1, 2, 3, or ≥4. The primary outcome was favorable functional outcome defined as modified Rankin Scale score of 0 to 3 at 90 days. Safety outcomes were symptomatic intracranial hemorrhage after 24 hours and death within 90 days. Multivariable logistic regression was used to identify independent determinants of primary and secondary outcomes. RESULTS: A total of 348 patients met the inclusion criteria. Successful reperfusion was observed in 83.3% and favorable functional outcomes in 36.2%. Successful reperfusion at attempts 1 (adjusted odds ratio, 5.97 [95% CI, 1.71-24.43]; P=0.008) and 2 (adjusted odds ratio, 6.32 [95% CI, 1.73-26.92]; P=0.008) increased the odds of favorable functional outcome, whereas success at attempts 3 or ≥4 did not. Patients with >2 attempts showed higher rates of symptomatic intracranial hemorrhage (12.8% versus 6.5%; P=0.046). Successful reperfusion at any attempt lowered the odds of death compared with unsuccessful reperfusion. CONCLUSIONS: In patients with large vessel occlusion and Alberta Stroke Program Early Computed Tomography Score of 3 to 5, the clinical benefit of endovascular therapy was linked to the number of recanalization attempts required for successful reperfusion. Our findings encourage to perform at least 2 recanalization attempts to seek for successful reperfusion in large ischemic strokes, while >2 attempts should follow a careful risk-benefit assessment in these highly affected patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Thrombectomy for M2 Occlusions: Predictors of Successful and Futile Recanalization.

BACKGROUND: Patient-specific factors associated with successful recanalization in mechanical thrombectomy (MT) have been evaluated for acute ischemic stroke with large vessel occlusion. However, MT for M2 occlusions is still a matter of debate, and predictors of successful and futile recanalization have not been assessed in detail. We sought to identify predictors of recanalization success in patients with M2 occlusions undergoing MT based on large-scale clinical data. METHODS: All patients prospectively enrolled in the German Stroke Registry (May, 2015 to December, 2021) were screened (N=13 082). Inclusion criteria for the complete case analysis were isolated M2 occlusions. Standard descriptive statistics and multivariable logistic regression analysis were used to identify factors associated with successful recanalization (Thrombolysis in Cerebral Infarction [TICI]≥2b), complete recanalization (TICI=3) and futile recanalization (TICI≥2b with 90-day modified Rankin Scale [mRS] score >2). RESULTS: One thousand two hundred ninety-four patients were included, thereof 439 (33.9%) with TICI=2b and 643 (49.7%) with TICI=3. Five hundred sixty-nine (44%) patients had good functional outcome (90-day mRS score ≤2). In multivariable logistic regression, general anesthesia (adjusted odds ratio [aOR], 1.47 [95% CI, 1.05-2.09]; P<0.05) was associated with higher probability of TICI≥2b while intraprocedural change from local to general anesthesia (aOR, 0.49 [0.26-0.95]; P<0.05) and higher pre-mRS (aOR, 0.75 [0.67-0.85]; P<0.001) lowered probability of successful recanalization. Futile recanalization was associated with higher age (aOR, 1.05 [1.04-1.07]; P<0.001), higher prestroke mRS (aOR, 3.12 [2.49-3.91]; P<0.001), higher NIHSS at admission (aOR, 1.11 [1.08-1.14]; P<0.001), diabetes (aOR, 1.96 [1.38-2.8]; P<0.001), higher number of passes (aOR, 1.29 [1.14-1.46]; P<0.001), and adverse events (aOR, 1.82 [1.2-2.74]; P<0.01). Higher Alberta Stroke Program Early CT Score (aOR, 0.85 [0.76-0.94]; P<0.01) and IV thrombolysis (aOR, 0.71 [0.52-0.97]; P<0.05) reduced risk of futile recanalization. CONCLUSIONS: In patients with M2 occlusions, successful recanalization was significantly associated with general anesthesia and low prestroke mRS, while intraprocedural change from conscious sedation to general anesthesia increased risk of unsuccessful recanalization, presumably caused by difficult anatomy and movement of patients in these cases. Futile recanalization was associated with severe prestroke mRS, comorbidity diabetes, number of passes and adverse events during treatment. IV thrombolysis reduced the risk of futile recanalization.

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

BACKGROUND: Follow-up infarct volume (FIV) is used as surrogate for treatment efficiency in mechanical thrombectomy (MT). However, previous works suggest that MT-related FIV reduction has only limited association with outcome comparing MT independently of recanalization success versus medical care. It remains unclear to what extent the relationship between successful recanalization versus persistent occlusion and functional outcome is explained by FIV reduction. OBJECTIVE: To determine whether FIV mediates the relationship between successful recanalization and functional outcome. METHODS: All patients from our institution enrolled in the German Stroke Registry (May 2015-December 2019) with anterior circulation stroke; availability of the relevant clinical data, and follow-up-CT were analyzed. The effect of FIV reduction on functional outcome (90-day modified Rankin Scale (mRS) score ≤2) after successful recanalization (Thrombolysis in Cerebral Infarction ≥2b) was quantified using mediation analysis. RESULTS: 429 patients were included, of whom, 309 (72 %) had successful recanalization and 127 (39%) had good functional outcome. Good outcome was associated with age (OR=0.89, P<0.001), pre-stroke mRS score (OR=0.38, P<0.001), FIV (OR=0.98, P<0.001), hypertension (OR=2.08, P<0.05), and successful recanalization (OR=3.57, P<0.01). Using linear regression in the mediator pathway, FIV was associated with Alberta Stroke program Early CT Score (coefficient (Co)=-26.13, P<0.001), admission National Institutes of Health Stroke Scale score (Co=3.69, P<0.001), age (Co=-1.18, P<0.05), and successful recanalization (Co=-85.22, P<0.001). Successful recanalization increased the probability of good outcome by 23 percentage points (pp) (95% CI 16pp to 29pp). 56% (95% CI 38% to 78%) of the improvement in good outcome was explained by FIV reduction. CONCLUSION: 56% (95% CI 38% to 78%) of outcome improvement after successful recanalization was explained by FIV reduction. Results corroborate pathophysiological assumptions and confirm the value of FIV as an imaging endpoint in clinical trials. 44% (95% CI 22% to 62%) of the improvement in outcome was not explained by FIV reduction and reflects the remaining mismatch between radiological and clinical outcome measures.

Thrombectomy in M2 occlusion compared to M1 occlusion: treatment effects of Thrombolysis In Cerebral Infarction (TICI) 2b and TICI 3 recanalization on functional outcome.

BACKGROUND: Emerging data suggest that mechanical thrombectomy (MT) might also be safe and efficient for medium and distal occlusions. This study aims to compare average treatment effects on functional outcome of different degrees of recanalization after MT in patients with M2 occlusion and M1 occlusion. METHODS: All patients enrolled in the German Stroke Registry (GSR) between June 2015 and December 2021 were analyzed. Inclusion criteria were stroke with primary M1 occlusion or M2 occlusion, and availability of relevant clinical data. 4259 patients were included, thereof 1353 with M2 occlusion and 2906 with M1 occlusion. Treatment effects were analyzed using double-robust inverse-probability-weighted regression-adjustment (IPWRA) estimators to control for confounding covariates. Binarized endpoint metrics were defined as good outcome with modified Rankin Scale (mRS) ≤2 at 90 days, and linearized endpoint metrics were defined as mRS shift pre-stroke to 90 days. Effects were evaluated for near complete recanalization (Thrombolysis In Cerebral Infarction scale (TICI) 2b) and complete recanalization (TICI 3). RESULTS: Treatment effect estimation for TICI ≥2b versus TICI <2b in M2 occlusions showed an increase in the probability of a good outcome from 27% to 47% with a number-needed-to-treat (NNT) of 5. For M1 occlusions the probability of a good outcome increased from 16% to 38% with NNT 4.5. TICI 3 versus TICI 2b increased the probability of a good outcome by 7 percentage points in M1 occlusions; for M2 occlusions the beneficial effect was not significant. CONCLUSIONS: Results suggest that successful recanalization with TICI ≥2b versus TICI <2b after MT in M2 occlusions provides significant patient benefit with treatment effects comparable to M1 occlusions. The probability of functional independence increased by 20 percentage points (NNT 5) and stroke-related mRS increase was reduced by 0.9 mRS points. In contrast to M1 occlusions, complete recanalization TICI 3 versus TICI 2b had lower additional beneficial effect.

Benefit and risk of intravenous alteplase in patients with acute large vessel occlusion stroke and low ASPECTS.

BACKGROUND: The benefit of best medical treatment including intravenous alteplase (IVT) before mechanical thrombectomy (MT) in patients with acute ischemic stroke and extensive early ischemic changes on baseline CT remains uncertain. The purpose of this study was to evaluate the benefit of IVT for patients with low ASPECTS (Alberta Stroke Programme Early CT Score) compared with patients with or without MT. METHODS: This multicenter study pooled consecutive patients with anterior circulation acute stroke and ASPECTS≤5 to analyze the impact of IVT on functional outcome, and to compare bridging IVT with direct MT. Functional endpoints were the rates of good (modified Rankin Scale (mRS) score ≤2) and very poor (mRS ≥5) outcome at day 90. Safety endpoint was the occurrence of symptomatic intracranial hemorrhage (sICH). RESULTS: 429 patients were included. 290 (68%) received IVT and 168 (39%) underwent MT. The rate of good functional outcome was 14.4% (95% CI 7.1% to 21.8%) for patients who received bridging IVT and 24.4% (95% CI 16.5% to 32.2%) for those who underwent direct MT. The rate of sICH was significantly higher in patients with bridging IVT compared with direct MT (17.8% vs 6.4%, p=0.004). In multivariable logistic regression analysis, IVT was significantly associated with very poor outcome (OR 2.22, 95% CI 1.05 to 4.73, p=0.04) and sICH (OR 3.44, 95% CI 1.18 to 10.07, p=0.02). Successful recanalization, age, and ASPECTS were associated with good functional outcome. CONCLUSIONS: Bridging IVT in patients with low ASPECTS was associated with very poor functional outcome and an increased risk of sICH. The benefit of this treatment should therefore be carefully weighed in such scenarios. Further randomized controlled trials are required to validate our findings.

Transferring neurointerventionalists saves time compared with interhospital transfer of stroke patients for endovascular thrombectomy: a collaborative pooled analysis of 1001 patients (EVEREST).

BACKGROUND: Interhospital transfer of stroke patients (drip and ship concept) is associated with longer treatment times compared with primary admission to a comprehensive stroke center (mothership concept). In recent years, studies on a novel concept of performing endovascular thrombectomy (EVT) at external hospitals (EXT) by transferring neurointerventionalists, instead of patients, have been published. This collaborative study aimed at answering the question of whether EXT saves time in the workflow of acute stroke treatment across various geographical regions. METHODS: This was a patient level pooled analysis of one prospective observational study and four retrospective cohort studies, the EVEREST collaboration (EndoVascular thrombEctomy at Referring and External STroke centers). Time from initial stroke imaging to EVT (vascular puncture) was compared in mothership, drip and ship, and EXT concepts. RESULTS: In total, 1001 stroke patients from various geographical regions who underwent EVT due to large vessel occlusion were included. These were divided into mothership (n=162, 16.2%), drip and ship (n=458, 45.8%), and EXT (n=381, 38.1%) cohorts. The median time periods from onset to EVT (195 min vs 320 min, p<0.001) and from imaging to EVT (97 min vs 184 min, p<0.001) in EXT were significantly shorter than for drip and ship thrombectomy concept. CONCLUSIONS: This pooled analysis of the EVEREST collaboration adds evidence that performing EVT at external hospitals can save time compared with drip and ship across various geographical regions. We encourage conducting randomized controlled trials comparing both triage concepts.

Endovascular treatment of acute tandem lesions in patients with mild anterior circulation stroke.

BACKGROUND: In patients with mild strokes the risk-benefit ratio of endovascular treatment (EVT) for tandem lesions has yet to be evaluated outside of current guideline recommendations. This study investigates the frequency as well as procedural and safety outcomes in daily clinical practice. METHODS: Using data from the German Stroke Registry-Endovascular Treatment (GSR-ET) we analyzed patients with anterior circulation stroke due to tandem-lesions and mild deficits. These patients were defined as ≤5 on the National Institutes of Health Stroke Scale (NIHSS). Recanalization was assessed with the modified Thrombolysis in Cerebral Infarction Scale (mTICI). Early neurological and long-term functional outcomes were assessed with the NIHSS change and modified Rankin scale (mRS), respectively. Safety assessment included periprocedural complications and the rate of symptomatic intracerebral hemorrhage (sICH). RESULTS: A total of 61 patients met the inclusion criteria and were treated endovascularly for tandem lesions. The median age was 68 (IQR:59-76) and 32.9% (20) were female. Patients were admitted to the hospital with a median NIHSS score of 4 (IQR:2-5) and a median Alberta Stroke Programme Early CT Score (ASPECTS) of 9 (IQR:8-10). Successful recanalization (mTICI 2b-3) was observed in 86.9% (53). NIHSS decreased non-significantly (p=0.382) from baseline to two points (IQR:1-9) at discharge. Excellent (mRS≤1) and favorable (mRS≤2) long-term functional outcome at 90-days was 55.8% (29) and 69.2% (36), respectively. Mortality rates at 90-days were 9.6% (5) and sICH occurred in 8.2% (5). CONCLUSIONS: EVT for tandem lesions in patients with mild anterior circulation stroke appears to be feasible but may lead to increased rates of sICH. Further studies comparing endovascular with best medical treatment (BMT) especially investigating the risk of periprocedural hemorrhagic complications, are needed.

Side matters: differences in functional outcome and quality of life after thrombectomy in left and right hemispheric stroke.

BACKGROUND: Patients with a left (LHS) or right hemispheric stroke (RHS) differ in terms of clinical symptoms due to lateralization of specific cortical functions. Studies on functional outcome after stroke and endovascular thrombectomy (EVT) comparing both hemispheres showed conflicting results so far. The impact of stroke laterality on patient-reported health-related quality of life (HRQoL) after EVT has not yet been adequately addressed and still remains unclear. METHODS: Consecutive stroke thrombectomy patients, derived from a multi-center, prospective registry (German Stroke Registry) between June 2015 and December 2019, were included in this study. At 90 days, outcome after EVT was assessed by the modified Rankin scale (mRS) and HRQoL using the European QoL-five dimensions questionnaire utility-index (EQ-5D-I; higher values indicate better HRQoL) in patients with LHS and RHS. Adjusted regression analysis was applied to evaluate the influence of stroke laterality on outcome after EVT. RESULTS: In total, 5683 patients were analyzed. Of these, 2953 patients (52.8%) had LHS and 2637 (47.2%) RHS. LHS patients had a higher baseline NIHSS (16 vs. 13, p < 0.001) and a higher ASPECTS (9 vs. 8, p < 0.001) compared to RHS patients. Among survivors, patients with LHS less frequently had a self-reported affected mobility (p = 0.037), suffered less often from pain (p = 0.04) and anxiety/depression (p = 0.032) three months after EVT. After adjusting for confounders (age, sex, baseline NIHSS), LHS was associated with a better HRQoL (ß coefficient 0.04, CI 95% 0.017-0.063; p = 0.001), and better functional outcome assessed by lower values on the mRS (ß coefficient - 0.109, CI 95% - 0.217-0.000; p = 0.049). CONCLUSIONS: Ninety days after EVT, LHS patients have a better functional outcome and HRQoL. Patients with RHS should be actively assessed and treated for pain, anxiety and depression to improve their HRQoL after EVT.

Association of Thrombectomy With Functional Outcome for Patients With Ischemic Stroke Who Presented in the Extended Time Window With Extensive Signs of Infarction.

Importance: Only limited data are available about a potential benefit associated with endovascular treatment (EVT) for patients with ischemic stroke presenting in the extended time window who also show signs of extensive infarction. Objective: To assess the association of recanalization after EVT with functional outcomes for patients with ischemic stroke presenting in the extended time window who also show signs of extensive infarction. Design, Setting, and Participants: This retrospective, multicenter cohort study included patients enrolled in the German Stroke Registry-Endovascular Treatment with an Alberta Stroke Program Early CT Score (ASPECTS) of 5 or less who presented between 6 and 24 hours after stroke onset and underwent computed tomography and subsequent EVT between July 1, 2015, and December 31, 2019. Main Outcomes and Measures: The primary end point was a modified Rankin Scale (mRS) score of 3 or less at day 90. The association between recanalization (defined as the occurrence of a modified Thrombolysis in Cerebral Infarction Scale score of 2b or 3) and outcome was assessed using logistic regression and inverse probability weighting analysis. Intervention: Endovascular treatment. Results: Of 5853 patients, 285 (5%; 146 men [51%]; median age, 73 years [IQR, 62-81 years]) met the inclusion criteria and were analyzed. Of these 285 patients, 79 (27.7%) had an mRS score of 3 or less at day 90. The rate of successful recanalization was 75% (215 of 285) and was independently associated with a higher probability of reaching an mRS score of 3 or less (adjusted odds ratio, 4.39; 95% CI, 1.79-10.72; P < .001). In inverse probability weighting analysis, a modified Thrombolysis in Cerebral Infarction Scale score of 2b or 3 was associated with a 19% increase (95% CI, 9%-29%; P < .001) in the probability for an mRS score of 3 or more. Multivariable logistic regression analysis suggested a significant treatment benefit associated with vessel recanalization in a time window of up to 17.6 hours and ASPECTS of 3 to 5. The rate of secondary symptomatic intracerebral hemorrhage was 6.3% (18 of 285). Conclusions and Relevance: In this cohort study reflecting daily clinical practice, vessel recanalization for patients with a low ASPECTS and extended time window was associated with better functional outcomes in a time window up to 17.6 hours and ASPECTS of 3 to 5. The results of this study encourage current randomized clinical trials to enroll patients with a low ASPECTS, even within the extended time window.

Early surrogates of outcome after thrombectomy in posterior circulation stroke.

BACKGROUND: Early surrogates for functional outcome in anterior circulation stroke have been described with the National Institute of Health Stroke Scale (NIHSS) at 24 h being reported as the most accurate metric. We compare discriminatory power of established definitions of early neurological improvement (ENI) and NIHSS scores at admission and 24 h to predict functional outcome at 90 days after thrombectomy in posterior circulation stroke (PCS). METHODS: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with PCS and at least vertebral or basilar artery occlusions were included. NIHSS admission, 24 h and ENI definitions (improvement of 8/10 NIHSS points or 0/1 NIHSS points at 24 h) were compared for predicting functional outcome at 90 days. Favourable and good outcome were defined as modified Rankin Scale (mRS) 0-2 and 0-3. Multivariable logistic regression analysis was conducted to identify factors impairing predictive power. RESULTS: Three hundred and eighty-seven patients were included. NIHSS 24 h had the highest discriminative power with receiver operator characteristics area under the curve of 0.87 (95% confidence interval: 0.83; 0.90) for good and 0.89 (0.85; 0.92) for favourable outcome; optimal cut-off values were ≤9 and ≤5. Higher age (odds ratio = 1.10 [1.05; 1.16]), adverse events during treatment (9.46 [1.52; 72.5]) and until discharge (18.34 [2.33; 172]) and high NIHSS scores at 24 h (1.29 [1.10; 1.53]) were independent predictors for turning the outcome prognosis from good (mRS ≤3) to poor (mRS ≥4). CONCLUSIONS: NIHSS 24 h ≤9 points serves best as surrogate for good functional outcome after thrombectomy in PCS. Advanced age, severe neurological symptoms at admission and adverse events decrease its predictive value.

How Much of the Thrombectomy Related Improvement in Functional Outcome Is Already Apparent at 24 Hours and at Hospital Discharge?

BACKGROUND: Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome. METHODS: All patients enrolled in the German Stroke Registry (June 2015-December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge). RESULTS: Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94-0.96]), prestroke modified Rankin Scale (0.48 [0.42-0.55]), admission-NIHSS (0.96 [0.94-0.98]), 24-hour NIHSS (0.83 [0.81-0.84]), diabetes (0.56 [0.43-0.72]), proximal middle cerebral artery occlusions (0.78 [0.62-0.97]), passes (0.88 [0.82-0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00-1.14]), successful recanalization (2.39 [1.68-3.43]), intracerebral hemorrhage (0.51 [0.35-0.73]), and recurrent strokes (0.54 [0.32-0.92]). Mediation analysis showed a 20 percentage points (95% CI' 17-24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI' 44%-66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI' 62%-90%) by NIHSS at hospital discharge. CONCLUSIONS: Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03356392.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.

Health-related quality of life after thrombectomy in young-onset versus older stroke patients: a multicenter analysis.

BACKGROUND: Information is lacking on self-reported health-related quality of life (HRQoL) as a complementary outcome measure in addition to the modified Rankin scale (mRS) in young patients with ischemic stroke after endovascular thrombectomy (EVT) compared with older patients. METHODS: Data on consecutive patients with stroke who underwent thrombectomy (June 2015-2019) from a multicenter prospective registry (German Stroke Registry) were analyzed. HRQoL was measured by the European QoL-5 dimension questionnaire utility index (EQ-5D-I; higher values indicate better HRQoL) 3 months after stroke in patients aged ≤55 and >55 years. Multivariate regression analyses identified predictors of better HRQoL. RESULTS: Of 4561 included patients, 526 (11.5%) were ≤55 years old. Young-onset patients had a better outcome assessed by mRS (mRS 0-2: 64.3% vs 31.8%, p<0.001) and EQ-5D-I (mean 0.639 vs 0.342, p<0.001). Young survivors after EVT had fewer complaints in the EQ-5D domains mobility (p<0.001), self-care (p<0.001), usual activities (p<0.001) and pain/discomfort (p=0.008), whereas no difference was observed in anxiety/depression (p=0.819). Adjusted regression analysis for 90-day mRS showed no difference in HRQoL between the two subgroups of patients. Lower age, National Institutes of Health Stroke Scale score and pre-stroke mRS, a higher Alberta Stroke Program Early CT Score, concomitant intravenous thrombolysis therapy and successful recanalization were associated with better HRQoL in both patient subgroups. CONCLUSIONS: Young-onset stroke patients have a better HRQoL after EVT than older patients. Their higher HRQoL is mainly explained by less physical disability assessed by mRS. Depressive symptoms should be actively assessed and targeted in rehabilitation therapies of young-onset stroke patients to improve quality of life after stroke.

Study Criteria Applied to Real Life-A Multicenter Analysis of Stroke Patients Undergoing Endovascular Treatment in Clinical Practice.

Background Randomized controlled clinical trials (RCT) have demonstrated the efficacy of endovascular treatment in anterior circulation large vessel occlusions. However, outcome of patients treated in daily practice differs from the results of the clinical trials. We hypothesize that this is attributable to the study criteria and that application of the criteria on patients undergoing endovascular therapy in daily routine would improve their outcome. Methods and Results Data from a multicenter prospective registry of GSR-ET (German Stroke Registry - Endovascular Treatment) was used. Inclusion criteria and selectivity of SWIFT-PRIME (Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment trial), MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands trial), ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times trial), DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo trial) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke trial) trials were analyzed. Baseline characteristics, procedural and outcome data of patients from GSR-ET before and after selection were compared with the results of the RCTs. Furthermore, outcome of patients who underwent endovascular treatment despite not fulfilling the RCT criteria was analyzed. A total of 2611 patients were included (median age, 75 years; 49.6% women; median National Institute of Health Stroke Scale, 16). A minority of patients met all inclusion criteria, ranging from 3% (DEFUSE-3 criteria) to 35% (MR CLEAN criteria). Of the patients fulfilling the MR CLEAN criteria, 41% of patients had a good clinical outcome, compared with 34% of patients that did not fulfill MR CLEAN criteria. Conclusions The RCTs represent a selected population with higher rates of good clinical outcome compared with daily practice. The good outcomes of RCTs can be reproduced in clinical routine in patients who fulfill the RCT inclusion criteria. Furthermore, patients who did not meet the criteria of the RCT still had substantial rates of good clinical outcome.

Thrombectomy in Extensive Stroke May Not Be Beneficial and Is Associated With Increased Risk for Hemorrhage.

Background and Purpose: This study evaluates the benefit of endovascular treatment (EVT) for patients with extensive baseline stroke compared with best medical treatment. Methods: This retrospective, multicenter study compares EVT and best medical treatment for computed tomography (CT)­based selection of patients with extensive baseline infarcts (Alberta Stroke Program Early CT Score ≤5) attributed to anterior circulation stroke. Patients were selected from the German Stroke Registry and 3 tertiary stroke centers. Primary functional end points were rates of good (modified Rankin Scale score of ≤3) and very poor outcome (modified Rankin Scale score of ≥5) at 90 days. Secondary safety end point was the occurrence of symptomatic intracerebral hemorrhage. Angiographic outcome was evaluated with the modified Thrombolysis in Cerebral Infarction Scale. Results: After 1:1 pair matching, a total of 248 patients were compared by treatment arm. Good functional outcome was observed in 27.4% in the EVT group, and in 25% in the best medical treatment group (P=0.665). Advanced age (adjusted odds ratio, 1.08 [95% CI, 1.05­1.10], P<0.001) and symptomatic intracerebral hemorrhage (adjusted odds ratio, 6.35 [95% CI, 2.08­19.35], P<0.001) were independently associated with very poor outcome. Mortality (43.5% versus 28.9%, P=0.025) and symptomatic intracerebral hemorrhage (16.1% versus 5.6%, P=0.008) were significantly higher in the EVT group. The lowest rates of good functional outcome (≈15%) were observed in groups of failed and partial recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 0/1­2a), whereas patients with complete recanalization (modified Thrombolysis in Cerebral Infarction Scale score of 3) with recanalization attempts ≤2 benefitted the most (modified Rankin Scale score of ≤3:42.3%, P=0.074) compared with best medical treatment. Conclusions: In daily clinical practice, EVT for CT­based selected patients with low Alberta Stroke Program Early CT Score anterior circulation stroke may not be beneficial and is associated with increased risk for hemorrhage and mortality, especially in the elderly. However, first- or second-pass complete recanalization seems to reveal a clinical benefit of EVT highlighting the vulnerability of the low Alberta Stroke Program Early CT Score subgroup. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.