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Purpose: Randomized controlled trials (RCTs) demonstrated a treatment effect of endovascular thrombectomy in acute ischemic stroke with large infarct, commonly defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. However, data on endovascular thrombectomy in patients with very low ASPECTS of 0-2 remain scarce., Methods: We conducted a systematic review and meta-analysis of RCTs comparing endovascular thrombectomy versus medical treatment alone in acute ischemic anterior circulation stroke with very large infarct, defined as ASPECTS of 0-2. The primary outcome was the shift toward better functional outcomes on the 90-day modified Rankin Scale (mRS). Random effects meta-analysis was performed using the generic inverse variance method., Results: Literature research identified four RCTs which evaluated the treatment effect of endovascular thrombectomy for large infarcts and provided a subgroup analysis of the mRS shift in patients with ASPECTS of 0-2. The pooled analysis showed a significant shift toward better 90-day mRS scores in favor of endovascular thrombectomy (pooled odds ratio, 1.62, 95% confidence interval, 1.29-2.04, P < 0.001)., Conclusion: This meta-analysis suggests a treatment effect of endovascular thrombectomy in specific patients with very low ASPECTS of 0-2, challenging the use of ASPECTS for treatment selection in acute ischemic stroke due to large vessel occlusion. An individual patient meta-analysis of RCTs would strengthen evidence in the treatment of patients with ASPECTS of 0-2., (© 2024. The Author(s).)

Background: The proper imaging modality for use in the selection of patients for endovascular thrombectomy (EVT) presenting in the late window remains controversial, despite current guidelines advocating the use of advanced imaging in this population. We sought to understand if clinicians with different specialty training differ in their approach to patient selection for EVT in the late time window., Methods: We conducted an international survey of stroke and neurointerventional clinicians between January and May 2022 with questions focusing on imaging and treatment decisions of large vessel occlusion (LVO) patients presenting in the late window. Interventional neurologists, interventional neuroradiologists, and endovascular neurosurgeons were defined as interventionists whereas all other specialties were defined as non-interventionists. The non-interventionist group was defined by all other specialties of the respondents: stroke neurologist, neuroradiologist, emergency medicine physician, trainee (fellows and residents) and others., Results: Of 3000 invited to participate, 1506 (1027 non-interventionists, 478 interventionists, 1 declined to specify) physicians completed the study. Interventionist respondents were more likely to proceed directly to EVT (39.5% vs. 19.5%; p < 0.0001) compared to non-interventionist respondents in patients with favorable ASPECTS (Alberta Stroke Program Early CT Score). Despite no difference in access to advanced imaging, interventionists were more likely to prefer CT/CTA alone (34.8% vs. 21.0%) and less likely to prefer CT/CTA/CTP (39.1% vs. 52.4%) for patient selection (p < 0.0001). When faced with uncertainty, non-interventionists were more likely to follow clinical guidelines (45.1% vs. 30.2%) while interventionists were more likely to follow their assessment of evidence (38.7% vs. 27.0%) (p < 0.0001)., Conclusion: Interventionists were less likely to use advanced imaging techniques in selecting LVO patients presenting in the late window and more likely to base their decisions on their assessment of evidence rather than published guidelines. These results reflect gaps between interventionists and non-interventionists reliance on clinical guidelines, the limits of available evidence, and clinician belief in the utility of advanced imaging., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Comorbidities and polypharmacy are risk factors for worse outcome in stroke. However, comorbidities and polypharmacy are mostly studied separately with various approaches to assess them. We aimed to analyze the impact of comorbidity burden and polypharmacy on functional outcome in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT)., Methods: Acute ischemic stroke patients with large vessel occlusion (LVO) treated with MT from a prospective observational study were analyzed. Relevant comorbidity burden was defined as a Charlson Comorbidity Index (CCI) score ≥ 2, polypharmacy as the intake of ≥ 5 medications at time of stroke onset. Favorable outcome was a score of 0-2 on the modified Rankin scale at 90 days after stroke. The effect of comorbidity burden and polypharmacy on favorable outcome was studied via multivariable regression analysis., Results: Of 903 patients enrolled, 703 AIS patients (mean age 73.4 years, 54.9% female) with anterior circulation LVO were included. A CCI ≥ 2 was present in 226 (32.1%) patients, polypharmacy in 315 (44.8%) patients. Favorable outcome was less frequently achieved in patients with a CCI ≥ 2 (47, 20.8% vs. 172, 36.1%, p < 0.001), and in patients with polypharmacy (69, 21.9% vs. 150, 38.7%, p < 0.001). In multivariable regression analysis including clinical covariates, a CCI ≥ 2 was associated with lower odds of favorable outcome (odds ratio, OR 0.52, 95% confidence interval, 95% CI 0.33-0.82, p = 0.005), while polypharmacy was not (OR 0.81, 95% CI 0.52-1.27, p = 0.362)., Conclusion: Relevant comorbidity burden and polypharmacy are common in AIS patients with LVO, with comorbidity burden being a risk factor for poor outcome., (© 2022. The Author(s).)

Purpose: In mechanical thrombectomy, it has been hypothesized that multiple retrieval attempts might the improve reperfusion rate but not the clinical outcome. In order to assess a potential harmful effect of a mechanical thrombectomy on patient outcome, the number of retrieval attempts was analyzed. Only patients with a thrombolysis in cerebral infarction (TICI) score of 0 were reviewed to exclude the impact of eventual successful reperfusion on the mechanical hazardousness of repeated retrievals., Methods: In this study 6635 patients who underwent endovascular thrombectomy (EVT) for acute large vessel occlusion (LVO) from the prospectively administered multicenter German Stroke Registry were screened. Insufficient reperfusion was defined as no reperfusion (TICI score of 0), whereas a primary outcome was defined as functional independence (modified Rankin scale [mRS] 0-2 at day 90). Propensity score matching and multivariable logistic regressions were then performed to adjust for confounders., Results: A total of 377 patients (7.8%) had a final TICI score of 0 and were included in the study. After propensity score matching functional independence was found to be significantly more frequent in patients who underwent ≤ 2 retrieval attempts (14%), compared to patients with > 2 retrieval attempts (3.9%, OR 0.29, 95% CI 0.07-0.73, p = 0.009). After adjusting for age, sex, admission NIHSS score, and location of occlusion, more than two retrieval attempts remained significantly associated with lower odds of functional independence at 90 days (OR 0.2, 95% CI 0.07-0.52, p = 0.002)., Conclusion: In patients with failure of reperfusion, more than two retrieval attempts were associated with a worse clinical outcome, therefore indicating a possible harmful effect of multiple retrieval attempts., (© 2021. The Author(s).)

Background and Purpose: A Thrombolysis in Cerebral Infarction (TICI) score of 3 has been established as therapeutic goal in endovascular therapy (EVT) for acute ischemic stroke; however, in the case of early TICI2b reperfusion, the question remains whether to stop the procedure or to continue in the pursuit of perfection (i.e., TICI 2c/3)., Methods: A total of 6635 patients were screened from the German Stroke Registry. Patients who underwent EVT for occlusion of the middle cerebral artery (M1 segment), with final TICI score of 2b/3 were included. Multivariable logistic regression was performed with functional independence (modified Rankin Scale, mRS at day 90 of 0-2) as the dependent variable., Results: Of 1497 patients, 586 (39.1%) met inclusion criteria with a final TICI score of 2b and 911 (60.9%) with a TICI score of 3. Patients who achieved first-pass TICI3 showed highest odds of functional independence (Odds ratio [OR] 1.71, 95% confidence interval [95% CI] 1.18-2.47). Patients who achieved TICI2b with the second pass (OR 0.53, 95% CI 0.31-0.89) or with three or more passes (OR 0.44, 95% CI 0.27-0.70) had significantly worse clinical outcomes compared to first-pass TICI2b. TICI3 at the second pass was by trend better than first-pass TICI2b (OR 1.55, 95% CI 0.98-2.45), but TICI3 after 3 or more passes (OR 0.93, 95% CI 0.57-1.50) was not significantly different from first-pass TICI2b., Conclusion: First-pass TICI2b was superior to TICI2b after ≥ 2 retrievals and comparable to TICI3 at ≥ 3 retrievals. The potential benefit in outcome after achieving TICI3 following further retrieval attempts after first-pass TICI2b need to be weighed against the risks., (© 2021. The Author(s).)

Introduction: Revascularization procedures in carotid artery stenosis have shown a positive effect in the restoration of cerebral oxygen metabolism as assessed by T2' (T2 prime) imaging as well as capillary homeostasis by measurement of capillary transit time heterogeneity (CTH); however, data in patients with asymptomatic carotid stenosis without manifest brain lesions are scarce., Patients and Methods: The effect of revascularization on the hemodynamic profile and capillary homeostasis was evaluated in 13 patients with asymptomatic high-grade carotid stenosis without ischemic brain lesions using dynamic susceptibility contrast perfusion imaging and oxygenation-sensitive T2' mapping before and 6-8 weeks after revascularization by endarterectomy or stenting. The cognitive performance at both timepoints was further assessed., Results: Perfusion impairment at baseline was accompanied by an increased CTH (p = 0.008) in areas with a time to peak delay ≥ 2 s in the affected hemisphere compared to contralateral regions. Carotid intervention improved the overall moderate hemodynamic impairment at baseline by leading to an increase in normalized cerebral blood flow (p = 0.017) and a decrease in mean transit time (p = 0.027), oxygen extraction capacity (OEC) (p = 0.033) and CTH (p = 0.048). The T2' values remained unchanged., Conclusion: This study presents novel evidence of a state of altered microvascular function in patients with high-grade carotid artery stenosis in the absence of ischemic brain lesions, which shows sustained normalization after revascularization procedures., (© 2021. The Author(s).)

Purpose: The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry., Methods: Data of consecutive stroke patients treated with thrombectomy (June 2015-April 2018) derived from an industry-independent registry (German Stroke Registry-Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale [mRS] 0-2) 90 days after stroke., Results: In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years; p < 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%; p < 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%; p < 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%; p = 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome., Conclusion: Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status., (© 2020. The Author(s).)

Purpose: Evaluating the extent of cerebral ischemic infarction is essential for treatment decisions and assessment of possible complications in patients with acute ischemic stroke. Patients are often triaged according to image-based early signs of infarction, defined by Alberta Stroke Program Early CT Score (ASPECTS). Our aim was to evaluate interrater reliability in a large group of readers., Methods: We retrospectively analyzed 100 investigators who independently evaluated 20 non-contrast computed tomography (NCCT) scans as part of their qualification program for the TENSION study. Test cases were chosen by four neuroradiologists who had previously scored NCCT scans with ASPECTS between 0 and 8 and high interrater agreement. Percent and interrater agreements were calculated for total ASPECTS, as well as for each ASPECTS region., Results: Percent agreements for ASPECTS ratings was 28%, with interrater agreement of 0.13 (95% confidence interval, CI 0.09-0.16), at zero tolerance allowance and 66%, with interrater agreement of 0.32 (95% CI: 0.21-0.44), at tolerance allowance set by TENSION inclusion criteria. ASPECTS region with highest level of agreement was the insular cortex (percent agreement = 96%, interrater agreement = 0.96 (95% CI: 0.94-0.97)) and with lowest level of agreement the M3 region (percent agreement = 68%, interrater agreement = 0.39 [95% CI: 0.17-0.61])., Conclusion: Interrater agreement reliability for total ASPECTS and study enrollment was relatively low but seems sufficient for practical application. Individual region analysis suggests that some are particularly difficult to evaluate, with varying levels of reliability. Potential impairment of the supraganglionic region must be examined carefully, particularly with respect to the decision whether or not to perform mechanical thrombectomy., (© 2021. The Author(s).)

Purpose: Prolonged transfer times between the primary stroke center (PSC) and the comprehensive stroke center (CSC) are one of the major causes of treatment delay for endovascular stroke treatment. We aimed to analyze the effect of the diurnal variations in traffic rates at weekdays and weekends on the catchment area size of three transportation paradigms, i.e. mothership, drip-and-ship (DS) and drip-and-drive (DD)., Methods: A conditional probability model that predicts the probability of good outcome for patients with suspected large vessel occlusion was used to analyze the prehospital stroke triage in northwest Germany and produce catchment area maps. Transportation times were calculated during each hour of a weekday and a Sunday using Google Maps. For comparison, real DD transportation times from our CSC in Hamburg-Eppendorf (blinded for review) to a PSC in Lüneburg were prospectively recorded., Result: On weekdays, the mothership catchment area was the largest (≥40,000 km 2 , 63%) except for a decrease during morning rush hours, when the DD catchment area was highest (30,879 km 2 , 48%). The DS catchment area was higher than the DD catchment area during the afternoon rush hours both during the week as well as on Sundays., Conclusion: Our study showed a considerable impact of the diurnal variations in traffic rate and direction of travel on optimal stroke transportation. Stroke systems of care should take real time traffic information into account., (© 2020. The Author(s).)

Aim: In acute large vessel occlusions, endovascular therapy (EVT) achieves flow restoration in the majority of cases; however, EVT fails to achieve sufficient reperfusion in a substantial minority of patients. This study aimed to identify predictors of failed reperfusion., Methods: In this study 2211 patients from the German Stroke Registry who received EVT for anterior circulation stroke were retrospectively analyzed. Failure of reperfusion was defined as thrombolysis in cerebral infarction (TICI) grades 0/1/2a, and sufficient reperfusion as TICI 2b/3. In 1629 patients with complete datasets, associations between failure of reperfusion and baseline clinical data, comorbidities, location of occlusion, and procedural data were assessed with multiple logistic regression., Results: Failure of reperfusion occurred in 371 patients (16.8%) and was associated with the following locations of occlusion: cervical internal carotid artery (ICA, adjusted odds ratio, OR 2.01, 95% confidence interval, CI 1.08-3.69), intracranial ICA without carotid T occlusion (adjusted OR 1.79, 95% CI 1.05-2.98), and M2 segment (adjusted OR 1.86, 95% CI 1.21-2.84). Failed reperfusion was also associated with cervical ICA stenosis (>70% stenosis, adjusted OR 2.90, 95% CI 1.69-4.97), stroke of other determined etiology by TOAST (Trial of ORG 10172 in acute stroke treatment) criteria (e.g. nonatherosclerotic vasculopathies, adjusted OR 2.73, 95% CI 1.36-5.39), and treatment given outside the usual working hours (adjusted OR 1.41, 95% CI 1.07-1.86). Successful reperfusion was associated with higher Alberta stroke program early CT score (ASPECTS) on initial imaging (adjusted OR 0.85, 95% CI 0.79-0.92), treatment with the patient under general anesthesia (adjusted OR 0.72, 95% CI 0.54-0.96), and concomitant ICA stenting in patients with ICA stenosis (adjusted OR 0.20, 95% CI 0.11-0.38)., Conclusion: Several factors are associated with failure of reperfusion, most notably occlusions of the proximal ICA and low ASPECTS on admission. Conversely, stent placement in the proximal ICA was associated with reperfusion success.

Purpose: Patients with basilar artery occlusion (BAO) were excluded from previous randomized controlled trials (RCTs) of endovascular treatment (ET) for acute ischemic stroke, but are commonly treated in clinical practice. This study aimed at analyzing predictors of functional outcome of ET in patients with BAO to improve patient selection for ET., Methods: Consecutive patients with BAO who received ET over a 2-year time period were prospectively studied. Baseline characteristics, procedural and outcome data were evaluated. Outcome was assessed by the modified Rankin Scale (mRS) 90 days after stroke. Multivariate regression analyses were performed to identify predictors of outcome across the range of the mRS, of poor outcome (mRS 5-6) and independent outcome (mRS 0-2)., Results: A total of 39 patients with BAO (median age: 75 years, 67% male) were included. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 24. Intravenous thrombolysis therapy (IVT) was administered in 56%. Successful recanalization assessed by a modified thrombolysis in cerebral infarction (TICI) score ≥2b was achieved in 82%. Independent outcome was observed in 30% of patients with successful recanalization, but in no patient with failed recanalization. Poor outcome was observed in 47% and 86%, respectively. Successful recanalization was associated with lower scores on the mRS at 90 days (p = 0.035), and failed recanalization was associated with an odds ratio of 13.6 for poor outcome (p = 0.036)., Conclusion: Reperfusion is the major predictor of functional outcome in BAO in clinical practice. Failed recanalization resulted in a 13-fold increase of the risk of poor outcome. Successful recanalization is crucial to achieve a better functional outcome in BAO.

Purpose: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI)., Methods: All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions., Results: Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years; p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4; p = 0.046), and-among those randomized-had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1; p = 0.011)., Conclusion: Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts.

Purpose: Stent-retriever thrombectomy (SRT) for acute intracranial large artery occlusion (LAO) may not result in permanent recanalization in rare cases, e.g. due to an underlying stenosis or dissection. In this specific patient group, rescue stent angioplasty (RSA) may be the only treatment option to achieve permanent vessel patency and potentially a good clinical outcome. To date, the experience with RSA is limited., Methods: In this retrospective analysis, interventional and clinical data of patients with acute intracranial LAO of the anterior and posterior circulation who underwent RSA after SRT due to an underlying lesion between 2012-2017 in four neurovascular centers were studied., Results: In this study 34 patients (mean age 67 years) were included whereby 18 patients had anterior circulation LAO and 16 patients posterior circulation LAO. The SRT maneuver count ranged between 1 and 15 (median 2). Indications for RSA were an immediate re-occlusion in 25 (74%), and a persistent high-grade stenosis in 9 patients (26%). The RSA was technically feasible in 33 patients (97%). A mTICI 2b/3 result was obtained in 26 patients (76%). Median onset-to-recanalization time was 248 min (range 80-650 min). After 3 months 10/34 patients (29%) had a good clinical outcome (modified Rankin Scale, mRS 0-2). In detail, 4/18 patients (22%) with anterior circulation LAO and 6/16 patients (38%) with posterior circulation LAO were functionally independent., Conclusion: The use of RSA can be considered for acute intracranial LAO in cases with immediate re-occlusion or high-grade stenosis after SRT alone.

Introduction: Magnetic resonance imaging (MRI) has an important impact in diagnosing primary angiitis of the central nervous system (PACNS). However, neuroradiologic findings may vary immensely, making an easy and definite diagnosis challenging., Methods: In this retrospective, single center study, we analyzed neuroradiologic findings of patients with PACNS diagnosed at our hospital between 2009 and 2014. Furthermore, we classified patients according to the affected vessel size and compared imaging characteristics between the subgroups., Results: Thirty-three patients were included (mean age 43 [±15.3] years, 17 females) in this study. Patients with positive angiographic findings were classified as either medium or large vessel PACNS and presented more ischemic lesions (p < 0.001) and vessel wall enhancement (p = 0.017) compared to patients with small vessel PACNS. No significant differences were detected for the distribution of contrast-enhancing lesions (parenchymal or leptomeningeal), hemorrhages, or lesions with mass effect. Twenty-five patients underwent brain biopsy. Patients with medium or large vessel PACNS were less likely to have positive biopsy results., Discussion: It is essential to differentiate between small and medium/large vessel PACNS since results in MRI, digital subtraction angiography and brain biopsy may differ immensely. Since image quality of MR scanners improves gradually and brain biopsy may often be nonspecific or negative, our results emphasize the importance of MRI/MRA in the diagnosis process of PACNS.

Purpose: Few magnetic resonance imaging (MRI) studies of stroke have evaluated the value of visual assessment of perfusion/diffusion mismatch, which is crucial for routine application. In this study an attempt was made to visually assess perfusion lesions resembling the acute clinical situation and identify parameters with the highest interobserver reliability when used to define a perfusion/diffusion mismatch and the highest accuracy for prediction of infarct growth., Methods: Magnetic resonance imaging was performed within 6 h of symptom onset and again 1-11 days thereafter in 86 consecutive stroke patients who received intravenous thrombolytic therapy. The MRI protocol included diffusion-weighted imaging apparent diffusion coefficient (DWI/ADC), fluid-attenuated inversion recovery (FLAIR) and perfusion imaging (PI). Maps for different perfusion parameters, e.g. cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were calculated. Areas of perfusion deficits of all perfusion parameters were visually compared to corresponding ADCs and final infarct size by two independent observers., Results: The final infarct size was overestimated by TTP (in 81/83 patients by raters 1 and 2, respectively), MTT (82/83) and CBF (65/74) lesions. The ADC lesions were rated smaller than the final infarct size in 43/38 cases by raters 1 and 2 and the CBV decrease was rated to underestimate final infarct size in 40/31 cases. The only significantly increased OR of 3.883 (95 % CI 1.466-10.819, p = 0.004, rater 1)/5.142 (95 % CI 1.828-15.142, p = 0.001, rater 2) for predicting infarct growth was observed for the presence of a CBV > ADC mismatch, which also showed the highest kappa value of 0.407., Conclusions: All mismatch patterns were prone to high interrater variability when assessed under conditions resembling the clinical setting. Of all tested mismatch patterns the CBV > ADC mismatch was the strongest predictor of lesion growth while visual assessment of TTP and CBF generally resulted in an overestimation of infarct sizes and the presence of a TTP > ADC or CBF > ADC mismatch was not significantly predictive for lesion growth. Visual inspection of these most commonly used mismatch patterns has a low value for the prediction of infarct growth and thus the estimation of the penumbra in ischemic stroke patients.