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.

Molecular monitoring of T-cell kinetics and migration in severe neurotoxicity after real-world CD19-specific chimeric antigen receptor T cell therapy.

CD19-specific chimeric antigen receptor (CD19-CAR) T-cell therapies mediate durable responses in late-stage B-cell malignancies, but can be complicated by a potentially severe immune effector cell-associated neurotoxicity syndrome (ICANS). Despite broad efforts, the precise mechanisms of ICANS are not entirely known, and resistance to current ICANSdirected therapies (especially corticosteroids) has been observed. Recent data suggest that inflammatory cytokines and/or targeting of cerebral CD19-expressing pericytes can disrupt the blood-brain barrier and facilitate influx of immune cells, including CAR T cells. However, specific tools for CD19-CAR T-cell analysis within often minute samples of cerebrospinal fluid (CSF) are not broadly available. Here, we applied our recently developed digital polymerase chain reaction assays to monitor CD19-CAR T-cell kinetics in CSF and blood in real-world patients with neurotoxicity. Consistently, we observed a CAR T-cell enrichment within CSF in ICANS patients with further progressive accumulation despite intense corticosteroid- containing immuno-chemotherapies in a subset of patients with prolonged and therapy-resistant grade 3-4 neurotoxicity. We used next-generation T-cell receptor-b sequencing to assess the repertoire of treatment-refractory cells. Longitudinal analysis revealed a profound skewing of the T-cell receptor repertoire, which at least partly reflected selective expansion of infused T-cell clones. Interestingly, a major fraction of eventually dominating hyperexpanded T-cell clones were of non-CAR T-cell derivation. These findings hint to a role of therapy-refractory T-cell clones in severe ICANS development and prompt future systematic research to determine if CAR T cells may serve as 'door openers' and to further characterize both CAR-positive and non-CAR T cells to interrogate the transcriptional signature of these possibly pathologic T cells.

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.

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.

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.

Ten Years of Improving Acute Stroke Management in a Metropolitan Area: A Population-Based Quantification of Quality Indicators.

BACKGROUND AND PURPOSE: Rapid access to acute stroke treatment improves clinical outcomes in patients with ischemic stroke. We aimed to shorten the time to admission and to acute stroke treatment for patients with acute stroke in the Hamburg metropolitan area by collaborative multilevel measures involving all hospitals with stroke units, the Emergency Medical Services (EMS), and health-care authorities. METHODS: In 2007, an area-wide stroke care quality project was initiated. The project included mandatory admission of all stroke patients in Hamburg exclusively to hospitals with stroke units, harmonized acute treatment algorithms among all hospitals, repeated training of the EMS staff, a multimedia educational campaign, and a mandatory stroke care quality monitoring system based on structured data assessment and quality indicators for procedural measures. We analyzed data of all patients with acute stroke who received inhospital treatment in the city of Hamburg during the evaluation period from the quality assurance database data and evaluated trends of key quality indicators over time. RESULTS: From 2007 to 2016, a total of 83,395 patients with acute stroke were registered. During this period, the proportion of patients admitted within ≤3 h from symptom onset increased over time from 27.8% in 2007 to 35.2% in 2016 (p < 0.001). The proportion of patients who received rapid thrombolysis (within ≤30 min after admission) increased from 7.7 to 54.1% (p < 0.001). CONCLUSIONS: Collaborative stroke care quality projects are suitable and effective to improve acute stroke care.

Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage.

Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. A direct association between the number of device passes and the occurrence of symptomatic intracranial hemorrhage (SICH) has been suggested. This study represents an in-depth investigation of the hypothesis that >3 retrieval attempts is associated with an increased rate of SICH in a large multicenter patient cohort. Two thousand six hundred eleven patients from the prospective German Stroke Registry were analyzed. Patients who received Endovascular therapy for acute large-vessel occlusion of the anterior circulation with known admission National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction, and number of retrieval passes were included. The primary outcome was defined as SICH. The secondary outcome was any type of radiologically confirmed intracranial hemorrhage within the first 24 hours. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers, as well as for confounders. Five hundred ninety-three patients fulfilled the inclusion criteria. The median number of retrieval passes was 2 [interquartile range, 1­3]. SICH occurred in 26 cases (4.4%), whereas intracranial hemorrhage was identified by neuroimaging in 85 (14.3%) cases. More than 3 retrieval passes was the strongest predictor for SICH (odds ratio, 3.61 [95% CI, 1.38­9.42], P=0.0089) following adjustment for age, admission National Institutes of Health Stroke Scale, admission Alberta Stroke Program Early CT Score, and Thrombolysis in Cerebral Infarction, as well as time from symptom onset to flow restoration. Baseline Alberta Stroke Program Early CT Score of 8 to 9 (odds ratio, 0.26 [95% CI, 0.07­0.89], P=0.032) or 10 (odds ratio, 0.21 [95% CI, 0.06­0.78], P=0.020) were significant protective factors against the occurrence of SICH. More than 3 retrieval attempts is associated with a significant increase in SICH risk, regardless of patient age, baseline National Institutes of Health Stroke Scale, or procedure time. This should be considered when deciding whether to continue a procedure, especially in patients with large baseline infarctions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Good Clinical Outcome Decreases With Number of Retrieval Attempts in Stroke Thrombectomy: Beyond the First-Pass Effect.

BACKGROUND AND PURPOSE: Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort. METHODS: For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders. RESULTS: The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 [95% CI, 4.0-10.4]), followed by the second attempt (adjusted odds ratio, 4.56 [95% CI, 2.7-7.7]), and finally the third (adjusted odds ratio, 3.16 [95% CI, 1.8-5.6]). CONCLUSIONS: Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Stroke Etiology Modifies the Effect of Endovascular Treatment in Acute Stroke.

Background and Purpose- Stroke etiology drives thrombus composition. We thus hypothesized that endovascular treatment shows different efficacy in cardioembolic versus noncardioembolic large-vessel occlusions (LVOs). Methods- Procedural characteristics, grade of reperfusion, and functional outcome at discharge and 90 days were compared between patients with cardioembolic versus noncardioembolic LVO from the GSR-ET (German Stroke Registry-Endovascular Treatment; n=2589). To determine associations with functional outcome, adjusted odds ratios and 95% CIs were calculated using ordinal multivariable logistic regression models adjusting for potential baseline confounder variables. Results- Endovascular treatment of cardioembolic LVO had a higher rate of successful reperfusion (85.6% versus 81.0%; P=0.002) and a higher rate of complete reperfusion after a single thrombectomy pass (45.7% versus 38.1%; P<0.001) compared with noncardioembolic LVO. Cardioembolic LVO was associated with better functional outcome at discharge (adjusted odds ratio, 1.61 [95% CI, 1.37-1.88]) and 90 days (adjusted odds ratio, 1.29 [95% CI, 1.09-1.53]). In mediation analysis, reperfusion explained 47% of the effect of etiology on functional outcome at discharge. Conclusions- These results provide evidence for higher efficacy of endovascular treatment in cardioembolic LVO compared with noncardioembolic LVO.

Early clinical surrogates for outcome prediction after stroke thrombectomy in daily clinical practice.

BACKGROUND AND PURPOSE: To investigate early clinical surrogates for long-term independency of patients treated with thrombectomy for large vessel occlusion stroke in daily clinical routine. METHODS: All patients with anterior circulation stroke enrolled in the German Stroke Registry-Endovascular Treatment from 07/2015 to 04/2018 were analysed. National Institute of Health Stroke Scale (NIHSS) on admission, NIHSS percentage change, NIHSS delta and NIHSS at 24 hours as well as existing binary definitions of early neurological improvement (ENI; improvement of 8 (major ENI)/10 (dramatic ENI) NIHSS points or reaching 0/1 were compared for predicting functional outcome at 90 days using the modified Rankin Scale (mRS). Excellent and favourable outcome were defined as 0-1 and 0-2, respectively. RESULTS: Among 2262 endovasculary treated patients with acute ischaemic anterior circulation stroke, NIHSS at 24 hours had the highest discriminative ability to predict excellent (receiver operator characteristics (ROC)NIHSS 24 hours area under the curve (AUC) 0.86 (0.84-0.88)) and favourable long-term functional outcome (ROCNIHSS 24 hours AUC 0.86 (0.85-0.88)) in comparison to NIHSS percentage change (ROC% change AUC mRS ≤1: 0.81 (0.78-0.83) mRS ≤2: 0.81 (0.79-0.83)), NIHSS delta change (ROCΔ change AUC mRS ≤1: 0.74 (0.72-0.77), mRS ≤2: 0.77 (0.74-0.79)) and NIHSS admission (ROCAdm AUC mRS ≤1: 0.70 (0.68-0.73), mRS ≤2: 0.67 (0.68-0.71)). Advanced age was the only independent predictor (adjusted OR 1.05, 95% CI 1.03 to 1.07, p<0.001) for turning the outcome prognosis from favourable (mRS ≤2) to poor (mRS ≥4) at 90 days. CONCLUSION: The NIHSS at 24 hours postintervention with a threshold of ≤8 points serves best as a surrogate for long-term functional outcome after thrombectomy for anterior circulation stroke in daily clinical practice. Only advanced age significantly decreases its predictive value.

Stroke patients treated by thrombectomy in real life differ from cohorts of the clinical trials: a prospective observational study.

BACKGROUND: Randomized controlled trials (RCTs) demonstrated efficacy and safety of endovascular treatment (ET) in anterior circulation large vessel occlusions (LVO). We aimed at investigating how stroke patients treated by thrombectomy in clinical practice and their outcome compare to cohorts and results of thrombectomy trials. METHODS: In a prospective study, we consecutively included stroke patients treated by thrombectomy (2015-2017). Baseline characteristics, procedural and outcome data were analyzed. Outcome was assessed by modified Rankin Scale (mRS) at 90 days. Ordinal regression analysis was performed to identify predictors of outcome. RESULTS: Thrombectomy was applied in 264 patients (median 75 years, 49.6% female). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16, 58.0% received concomitant intravenous thrombolysis, 62.1% were referred from external hospitals. Median Alberta Stroke Program Early CT Score (ASPECTS) was 7. Successful recanalization (modified Thrombolysis in Cerebral Infarction Score, mTICI 2b/3) was achieved in 72.0%. Symptomatic intracranial hemorrhage (sICH) occurred in 4.5%. Independent outcome (mRS 0-2) was achieved in 26.2%, poor outcome (mRS 5-6) in 49.2%. Only 33.5% met the stringent enrolment criteria of previous RCTs. Lower age, baseline NIHSS, pre-stroke mRS, higher ASPECTS, and successful recanalization were independent predictors of favourable outcome. CONCLUSIONS: The majority of stroke patients treated by ET in clinical practice would not have qualified for randomization in prior RCTs. Outcome in real-life patient cohorts is worse than in the highly selected cohorts from randomized trials, while rates of successful recanalization, sICH and outcome predictors are the same. Our findings support ET in broader patient populations than in the RCTs and may improve treatment decision in individual stroke patients with LVO in clinical practice.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Endovascular treatment of primary M3 occlusion stroke in clinical practice: analysis of the German Stroke Registry.

BACKGROUND: Endovascular treatment (ET) options for acute stroke due to distal middle cerebral artery occlusions are rapidly evolving, but data on outcome and safety are sparse. We therefore performed an analysis of patients undergoing ET for primary M3 occlusions in routine clinical practice in a nationwide registry. METHODS: Patients enrolled between 01/20 and 12/21 in the prospective, multicenter German Stroke Registry-Endovascular Treatment (GSR-ET) were screened for mechanical thrombectomy performed for primary M3 occlusion. We analyzed neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), thrombectomy technique, successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3) and functional outcome as measured by the modified Rankin Scale (mRS) at discharge and 90 days. RESULTS: Out of 5574 patients, 11 patients (0.2%, median age 80 years, 54.5% female) underwent ET for primary M3 occlusion. All patients had pre-admission mRS ≤ 1, median NIHSS on admission was 8, and successful reperfusion was achieved in 6/11 patients (54.5%). While no vasospasm, dissection or perforation was reported, symptomatic intracranial hemorrhage occurred in 2 patients (18.2%). Favorable outcome (mRS ≤ 2) was achieved in 6/11 patients (54.5%) at 90-day follow-up. CONCLUSIONS: ET for primary M3 occlusions is rarely performed. While technically feasible, the procedure's potential benefits must be carefully weighed against its associated risks, including clinically relevant complications. Caution and further research is needed to optimize patient selection for this intervention. TRIAL REGISTRATION: GSR-ET; ClinicalTrials.gov Identifier: NCT03356392; Trial Registration Date: 11/29/2017.

Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy : A Matched Case-control Analysis from the German Stroke Registry.

OBJECTIVE: Here we compare the procedural and clinical outcome of patients undergoing thrombectomy with running thrombolysis to matched controls with completed intravenous therapy and an only marginally overlapping activity. METHODS: Patients from 25 sites in Germany were included, who presented with an acute ischemic stroke. Patients' baseline characteristics (including ASPECTS, NIHSS and mRS), grade of reperfusion, and functional outcome 24 h and at day 90 after intervention were extracted from the German Stroke Registry (n = 2566). In a case-control design we stepwise matched the groups due to age, sex and time to groin puncture and time to flow restoration. RESULTS: In the initial cohort (overlap group n = 864, control group n = 1702) reperfusion status (median TICI in overlap group vs. control group: 3 vs. 2b), NIHSS after 24 h, early neurological improvement parameters, mRS at 24 h and at day 90 were significantly better in the overlap group (p < 0.001) with a similar risk of bleeding (2.9% vs. 2.4%) and death (18% vs. 22%). After adjustment mRS at day 90 still showed a trend for lower disability scores in the overlap group (3 IQR 1-5 vs. 3 IQR 1-6, p = 0.09). While comparable bleeding risk could be maintained (4% in both groups), there were significantly more deaths in the control group (18% vs. 30%, p = 0.006). CONCLUSION: The presented results support the approach of continuing and completing a simultaneous administration of intravenous thrombolysis during mechanical thrombectomy procedures.

Machine Learning-Based Identification of Target Groups for Thrombectomy in Acute Stroke.

Whether endovascular thrombectomy (EVT) improves functional outcome in patients with large-vessel occlusion (LVO) stroke that do not comply with inclusion criteria of randomized controlled trials (RCTs) but that are considered for EVT in clinical practice is uncertain. We aimed to systematically identify patients with LVO stroke underrepresented in RCTs who might benefit from EVT. Following the premises that (i) patients without reperfusion after EVT represent a non-treated control group and (ii) the level of reperfusion affects outcome in patients with benefit from EVT but not in patients without treatment benefit, we systematically assessed the importance of reperfusion level on functional outcome prediction using machine learning in patients with LVO stroke treated with EVT in clinical practice (N = 5235, German-Stroke-Registry) and in patients treated with EVT or best medical management from RCTs (N = 1488, Virtual-International-Stroke-Trials-Archive). The importance of reperfusion level on outcome prediction in an RCT-like real-world cohort equaled the importance of EVT treatment allocation for outcome prediction in RCT data and was higher compared to an unselected real-world population. The importance of reperfusion level was magnified in patient groups underrepresented in RCTs, including patients with lower NIHSS scores (0-10), M2 occlusions, and lower ASPECTS (0-5 and 6-8). Reperfusion level was equally important in patients with vertebrobasilar as with anterior LVO stroke. The importance of reperfusion level for outcome prediction identifies patient target groups who likely benefit from EVT, including vertebrobasilar stroke patients and among patients underrepresented in RCT patients with low NIHSS scores, low ASPECTS, and M2 occlusions.

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.

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.

Risk communication in acute stroke patients - from qualitative data to a pilot randomised controlled trial.

OBJECTIVES: The probability of recurring strokes in patients with atrial fibrillation is high. Within 1.8 years, 6.6 % of the patients suffered a new stroke. While effective secondary prevention options exist, low adherence challenges effective medical treatment. The aim of our study was to examine the risk understanding of acute stroke patients and to find the best way to communicate risk reduction. MATERIALS AND METHODS: Risk communication had three formats: a text, a pictogram, and a cube diagram. All three were developed on the basis of the criteria of evidence-based patient information. Patients who were admitted to the stroke unit and diagnosed with acute stroke, assessed the information material. Data on secondary prevention using acetylsalicylic acid were taken as an example, with no reference to actual patient treatment. In a first step, we interviewed a focus group to check the feasibility of the questionnaire (qualitative study). In the second step, the information material was tested in a pilot randomized controlled trial. RESULTS: Acute stroke patients (qualitative study, n=13) understood the information and were interested in numerical risk communication. The visualized representations were superior in terms of understandability of the numbers communicated (pilot randomized controlled trial, n=60, 50 % correct answers for question 1, p value of 0.502, and 55 % correct answers for question 2, p value of 0.338). Stroke-related neurologic deficits, measured with the National Institute of Health Stroke Scale (NIHSS) on admission, revealed a significant influence on the number of correct answers to stroke risk questions, whereas the type of stroke and education did not. CONCLUSIONS: Acute stroke patients were able to understand risk communication. Visualization helped them capture information on stroke risk.

Continuing early mTICI 2b recanalization may improve functional outcome but is associated with a higher risk of intracranial hemorrhage.

Background: Successful reperfusion (mTICI 2c/3) and low number of passes are key determinants for good clinical outcome in acute large vessel occlusion. While final mTICI 2c/3 reperfusion is superior to partial reperfusion (mTICI 2b) it remains unclear if this is also true for the subgroup of patients with early mTICI 2b (achieved in ≤2 retrieval attempts) reperfusion who are secondarily improved to mTICI 2c/3. This study was designed to examine if early mTICI2b should be continued or stopped during mechanical thrombectomy (MT). Methods: Nine hundred and thirteen ischemic stroke patients who received MT were retrospectively analyzed. Angiography runs following each recanalization attempt were scored for mTICI. The patients with early mTICI 2b reperfusions were dichotomized in "TICI2b-stopped" (MT withdrawal after mTICI 2b was achieved with first or second retrieval) and "TICI2b-continued" (MT was continued after mTICI 2b was achieved with first or second retrieval). Functional outcome was obtained after 90 days using the modified Rankin scale (mRS90). Results: Of 362 Patients with a M1-occlusion, 100 patients fulfilled the inclusion criteria with an early mTICI 2b. 78/100 patients were included in the "TICI2b-stopped" group and 22/100 patients were in the "TICI2b-continued" group. Of these 22 patients, none had a final mTICI score lower than 2b and 11 patients had a final mTICI score of 2c/3. Regarding good functional outcome at mRS90, "TICI2b-continued" showed by trend a slight advantage of 40.1 vs. 35.6% in "TICI2b-stopped" but in multivariate logistic regression analysis adjusted for confounders, no significant difference was found between the two groups (OR 0.75, 95% CI 0.19-2.87, p = 0.67). Symptomatic intracranial hemorrhage was significantly higher in "TICI2b-continued" compared to "TICI2b-stopped" (31.8 vs. 10.3%, p = 0.031). Conclusion: Successfully improving an early mTICI 2b to mTICI 2c/3 reperfusion is possible in a substantial number of patients and might improve functional outcome. However, an increase in symptomatic intracranial hemorrhage (SICH) due to further retrieval attempts may diminish the potential functional benefit to continue early mTICI 2b. To support this finding, further investigation with more power is needed to account for the low number of events regarding SICH.