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Background and aimIdentification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients.MethodsSVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression.ResultsOf the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45–6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73–13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54–2.11).ConclusionThe absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.

Digital subtraction angiography provides excellent spatial and temporal resolution; however, it lacks the capability to depict the nonvascular anatomy of the brain and spinal cord.A review of the institutional database identified five patients in whom a new integrated fusion workflow of cross-sectional imaging and 3D rotational angiography (3DRA) provided important diagnostic information and assisted in treatment planning. These included two acutely ruptured brain arteriovenous malformations (AVM), a small superficial brainstem AVM after radiosurgery, a thalamic microaneurysm, and a spine AVM, and fusion was crucial for diagnosis and influenced further treatment.Fusion of 3DRA and cross-sectional imaging may help to gain a deeper understanding of neurovascular diseases. This is advantageous for planning and providing treatment and, most importantly, may harbor the potential to minimize complication rates. Integrating image fusion in the work-up of cerebrovascular diseases is likely to have a major impact on the neurovascular field in the future.

Background and purpose 40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome. Materials and Methods Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0-2). Results In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02-1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27-3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41-1.24]) nor bridging IVT (aOR 1.08 [0.67-1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24-2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92). Conclusion Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT. Registration clinicaltrials.gov; Unique identifier: NCT03496064.

BackgroundNumerous questions regarding procedural details of distal stroke thrombectomy remain unanswered. This study assesses the effect of anesthetic strategies on procedural, clinical and safety outcomes following thrombectomy for distal medium vessel occlusions (DMVOs).MethodsPatients with isolated DMVO stroke from the TOPMOST registry were analyzed with regard to anesthetic strategies (ie, conscious sedation (CS), local (LA) or general anesthesia (GA)). Occlusions were in the P2/P3 or A2–A4 segments of the posterior and anterior cerebral arteries (PCA and ACA), respectively. The primary endpoint was the rate of complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3) and the secondary endpoint was the rate of modified Rankin Scale score 0–1. Safety endpoints were the occurrence of symptomatic intracranial hemorrhage and mortality.ResultsOverall, 233 patients were included. The median age was 75 years (range 64–82), 50.6% (n=118) were female, and the baseline National Institutes of Health Stroke Scale score was 8 (IQR 4–12). DMVOs were in the PCA in 59.7% (n=139) and in the ACA in 40.3% (n=94). Thrombectomy was performed under LA±CS (51.1%, n=119) and GA (48.9%, n=114). Complete reperfusion was reached in 73.9% (n=88) and 71.9% (n=82) in the LA±CS and GA groups, respectively (P=0.729). In subgroup analysis, thrombectomy for ACA DMVO favored GA over LA±CS (aOR 3.07, 95% CI 1.24 to 7.57, P=0.015). Rates of secondary and safety outcomes were similar in the LA±CS and GA groups.ConclusionLA±CS compared with GA resulted in similar reperfusion rates after thrombectomy for DMVO stroke of the ACA and PCA. GA may facilitate achieving complete reperfusion in DMVO stroke of the ACA. Safety and functional long-term outcomes were comparable in both groups.

BACKGROUND AND PURPOSE Malignancy associated acute ischemic stroke (AIS) requires specific diagnostic work-up, treatment and prevention to improve outcome. This study aimed to develop a biomarker-based score for prediction of occult malignancy in AIS patients. METHODS Single-center cross-sectional study including consecutive AIS patients treated between July 2017 and November 2018. Patients with active malignancy at presentation, or diagnosed within 1 year thereafter and patients free of malignancy, were included and malignancy associated biomarkers were assessed. LASSO analyses of logistic regression were performed to determine biomarkers predictive of active malignancy. Predictors were derived from a predictive model for active malignancy. A comparison between known and unknown (=occult) malignancies when the index stroke occurred was used to eliminate variables not associated with occult malignancy. A predictive score (OCCULT-5 score) for occult malignancy was developed based on the remaining variables. RESULTS From 1001 AIS patients, 61 (6%) presented an active malignancy. Thirty-nine (64%) were known and 22 (36%) occult. Five variables were included in the final OCCULT-5 score: age ≥ 77 years, embolic stroke of undetermined source, multi-territorial infarcts, D-dimer levels ≥ 820 µ/gL, and female sex. A score of ≥ 3 predicted an underlying occult malignancy with a sensitivity of 64%, specificity of 73%, positive likelihood ratio of 2.35 and a negative likelihood ratio of 0.50. CONCLUSIONS The OCCULT-5 score might be useful to identify patients with occult malignancy. It may thus contribute to a more effective and timely treatment and thus lead to a positive impact on overall outcome.

Background The National Institutes of Health Stroke Scale (NIHSS) obtained 24 hours after ischemic stroke is a good indicator for functional outcome and early mortality, but the correlation with long‐term survival is less clear. We analyzed the correlation of the NIHSS after 24 hours (24h NIHSS) and early clinical neurological development after mechanical thrombectomy with early and long‐term survival as well as its predictive power on survival. Methods We reviewed a prospective observational registry for all patients undergoing mechanical thrombectomy between January 2010 and December 2018. Vital status was extracted from the Swiss Population Registry. Adjusted hazard ratio (aHR) and crude hazard ratios were calculated using Cox regression. To assess predictive power of the 24h NIHSS, different Random Survival Forest models were evaluated. Results We included 957 patients (median follow‐up 1376 days). Patients with lower 24h NIHSS and major early neurological improvement had substantially better survival rates. We observed significantly higher aHR for death in patients with 24h NIHSS 12 to 15 (aHR, 1.78; 95% CI, 1.1–2.89), with 24h NIHSS 16 to 21 (aHR, 2.54, 95% CI, 1.59–4.06), and with 24h NIHSS >21 (aHR, 5.74; 95% CI, 3.47–9.5). The 24h NIHSS showed the best performance predicting mortality (receiver operating characteristic area under the curve at 3 months [0.85±0.034], at 1 year [0.82±0.029], at 2 years [0.82±0.031], and at 5 years [0.83±0.035]), followed by NIHSS change. Conclusions Patients with acute ischemic stroke achieving a low 24h NIHSS or major early neurological improvement after mechanical thrombectomy had markedly lower long‐term mortality. Furthermore, 24h NIHSS had the best predictive power for early and long‐term survival in our machine learning–based prediction.

BACKGROUND AND PURPOSE Whether intravenous thrombolysis (IVT) increases the risk for symptomatic intracranial hemorrhage (sICH) in patients treated with mechanical thrombectomy (MT) is a matter of debate. Purpose of this study was to evaluate the extent of early ischemia as a possible factor influencing the risk for sICH after IVT+MT versus direct MT. METHODS An explorative analysis of the BEYOND-SWIFT (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy) multicenter cohort was performed. We hypothesized that the sICH risk between IVT+MT versus direct MT differs across the strata of Alberta Stroke Program Early Computed Tomography Scores (ASPECTS). For this purpose, all patients with ICA, M1, and M2 vessel occlusions and available noncontrast computed tomography or diffusion-weighed imaging ASPECTS (n=2002) were analyzed. We used logistic regression analysis in subgroups, as well as interaction terms, to address the risk of sICH in IVT+MT versus direct MT patients across the ASPECTS strata. RESULTS In 2002 patients (median age, 73.7 years; 50.7% women; median National Institutes of Health Stroke Scale score, 16), the overall rate of sICH was 6.5% (95% CI, 5.5%-7.7%). Risk of sICH differed across ASPECTS groups (9-10: 6.3%; 6-8: 5.6% and ≤5 9.8%; P=0.042). With decreasing ASPECTS, the risks of sICH in the IVT+MT versus the direct MT group increased from adjusted odds ratio of 0.61 ([95% CI, 0.24-1.60] ASPECTS 9-10), to 1.72 ([95% CI, 0.69-4.24] ASPECTS 6-8) and 6.31 ([95% CI, 1.87-21.29] ASPECTS ≤5), yielding a positive interaction term (1.91 [95% CI, 1.01-3.63]). Sensitivity analyses regarding diffusion-weighed imaging versus noncontrast computed tomography ASPECTS did not alter the primary observations. CONCLUSIONS The extent of early ischemia may influence relative risks of sICH in IVT+MT versus direct MT patients, with an excess sICH risk in IVT+MT patients with low ASPECTS. If confirmed in post hoc analyses of randomized controlled trial data, IVT may be administered more carefully in patients with low ASPECTS eligible for and with direct access to MT.

BACKGROUND AND PURPOSE Treatment in stroke patients with M2 segment occlusion of the middle cerebral artery presenting with mild neurological deficits is a matter of debate. The main purpose was to compare the outcome in patients with a minor stroke and a M2 occlusion. METHODS Consecutive intravenous thrombolysis (IVT) eligible patients admitted to the Bernese stroke center between January 2005 and January 2020 with acute occlusion of the M2 segment and National Institutes of Health Stroke Scale score ≤5 were included. Outcome was compared between IVT only versus endovascular therapy (EVT) including intra-arterial thrombolysis and mechanical thrombectomy (MT; ±IVT) and between IVT only versus MT only. RESULTS Among 169 patients (38.5% women, median age 70.2 years), 84 (49.7%) received IVT only and 85 (50.3%) EVT (±IVT), the latter including 39 (45.9%) treated with MT only. Groups were similar in sex, age, vascular risk factors, event cause, or preevent independency. Compared with IVT only, there was no difference in favorable outcome (modified Rankin Scale score, 0-2) for EVT (adjusted odds ratio, 0.96; adjusted P=0.935) or for MT only (adjusted odds ratio, 1.12; adjusted P=0.547) groups. Considering only patients treated after 2015, there was a significantly better 3-month modified Rankin Scale shift (adjusted P=0.032) in the EVT compared with the IVT only group. CONCLUSIONS Our study demonstrates similar effectiveness of IVT only versus EVT (±IVT), and of IVT only versus MT only in patients with peripheral middle cerebral artery occlusions and minor neurological deficits and indicates a possible benefit of EVT considering only patients treated after 2015. There is an unmet need for randomized controlled trials in this stroke field, including imaging parameters, and more sophisticated evaluation of National Institutes of Health Stroke Scale score subitems, neurocognition, and quality of life neglected by the standard outcome scales such as modified Rankin Scale and National Institutes of Health Stroke Scale score.

BACKGROUND Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. METHODS We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). RESULTS The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. CONCLUSION The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.

BACKGROUND AND PURPOSE Data on safety and efficacy of intra-arterial (IA) fibrinolytics as adjunct to mechanical thrombectomy (MT) are sparse. METHODS INtra-arterial FIbriNolytics In ThrombectomY (INFINITY) is a retrospective multi-center observational registry of consecutive patients with anterior circulation large-vessel occlusion ischemic stroke treated with MT and adjunctive administration of IA fibrinolytics (alteplase [tissue plasminogen activator, tPA] or urokinase [UK]) at 10 European centers. Primary outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the European Cooperative Acute Stroke Study II definition. Secondary outcomes were mortality and modified Rankin Scale (mRS) scores at 3 months. RESULTS Of 5,612 patients screened, 311 (median age, 74 years; 44.1% female) received additional IA after or during MT (194 MT+IA tPA, 117 MT+IA UK). IA fibrinolytics were mostly administered for rescue of thrombolysis in cerebral infarction (TICI) 0-2b after MT (80.4%, 250/311). sICH occurred in 27 of 308 patients (8.8%), with an increased risk in patients with initial TICI0/1 (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1 to 5.0 per TICI grade decrease) or in those with intracranial internal carotid artery occlusions (aOR, 3.7; 95% CI, 1.2 to 12.5). In patients with attempted rescue of TICI0-2b and available angiographic follow-up, 116 of 228 patients (50.9%) showed any angiographic reperfusion improvement after IA fibrinolytics, which was associated with mRS ≤2 (aOR, 3.1; 95% CI, 1.4 to 6.9). CONCLUSIONS Administration of IA fibrinolytics as adjunct to MT is performed rarely, but can improve reperfusion, which is associated with better outcomes. Despite a selection bias, an increased risk of sICH seems possible, which underlines the importance of careful patient selection.