Collateral flow and pulsatility during large vessel occlusions: insights from a quantitative in vitro study.

Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient in vivo data on pathological collateral flow during large vessel occlusions are not available. Moreover, there are no flow models that accurately simulate the hemodynamic conditions in the CoW during large vessel occlusions. We used a circulatory loop to generate highly reproducible cerebrovascular-like flows and pressures and used non-invasive flow visualization and high-resolution flow and pressure measurements to acquire detailed, time-dependent hemodynamics inside an anatomical phantom of the CoW. After calibrating a physiological reference case, we induced occlusions in the 1. middle cerebral artery, 2. terminal carotid artery, and 3. basilar artery; and measured the left posterior communicating artery flow. Mean arterial pressure and pulse pressure remained unchanged in the different occlusion cases compared to the physiological reference case, while total cerebral flow decreased by up to 19%. In all three occlusion cases, reversed flow was found in the left posterior communicating artery compared to the reference case with different flow magnitudes and pulsatility index values. The experimental results were compared with clinical findings, demonstrating the capability of this realistic cerebrovascular flow setup. This novel cerebrovascular flow setup opens the possibility for investigating different topics of neurovascular interventions under various clinical conditions in controlled preclinical laboratory studies.

Blood-based frailty index in patients with acute ischemic stroke undergoing endovascular treatment.

INTRODUCTION: Frailty is a syndrome depicting vulnerability of multiple physiological systems to stressors. Frailty measures, such as Hospital Frailty Risk Score (HFRS), can be used to identify frailty and predict outcome more reliably. Our aim was to analyse a blood-based frailty index (FI-B) at admission for prediction outcome of patients with acute ischemic stroke (AIS) undergoing endovascular treatment (EVT). METHODS: We conducted a retrospective study of consecutive AIS patients undergoing EVT in a single tertiary centre during a period of five years. A set of eighteen blood parameters at admission were collected and nine of these were utilized to calculate FI-B. We analysed the relationship between FI-B and HFRS. We examined the baseline characteristics of the study population based on FI-B-tertiles. Multivariable regression models were employed to ascertain the association between FI-B and in-hospital mortality, 3-month mortality and 3-month functional outcome. RESULTS: The final study population comprised 489 patients, with a median age of 75.6 years, 49.5% of patients were male. The FI-B exhibited a weak positive correlation with HFRS (rho=0.113, p=0.016). Patients in higher FI-B-tertiles were older and more frequently presented with pre-stroke functional dependence and comorbidities. Moreover, an increasing FI-B was independently associated with increased likelihood of in-hospital mortality (adjusted odds ratio [aOR]=1.29, 95% confidence interval [95%CI]=1.14-1.47), 3-month mortality (aOR=1.26, 95%CI=1.11-1.43), and of increasing 3-month functional disability measured by utility-weighted modified Rankin Scale (common aOR=0.84, 95%CI=0.76-0.93). CONCLUSION: A frailty index based on blood values at admission was able to identify frailty in AIS patients undergoing EVT and was an independent predictor of short- and medium-term outcome after stroke.

Non-hemorrhagic imaging markers of cerebral amyloid angiopathy in memory clinic patients.

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.

Swallowing muscle mass contributes to post-stroke dysphagia in ischemic stroke patients undergoing mechanical thrombectomy.

BACKGROUND: Neurogenic dysphagia is a frequent complication of stroke and is associated with aspiration pneumonia and poor outcomes. Although ischaemic lesion location and size are major determinants of the presence and severity of post-stroke dysphagia, little is known about the contribution of other acute stroke-unrelated factors. We aimed to analyse the impact of swallowing and non-swallowing muscles measurements on swallowing function after large vessel occlusion stroke. METHODS: This retrospective study was based on a prospective registry of consecutive ischaemic stroke patients. Patients who underwent mechanical thrombectomy between July 2021 and June 2022 and received a flexible endoscopic evaluation of swallowing (FEES) within 5 days after admission were included. Demographic, anthropometric, clinical, and imaging data were collected from the registry. The cross-sectional areas (CSA) of selected swallowing muscles (as a surrogate marker for swallowing muscle mass) and of cervical non-swallowing muscles were measured in computed tomography. Skeletal muscle index (SMI) was calculated and used as a surrogate marker for whole body muscle mass. FEES parameters, namely, Functional Oral Intake Scale (FOIS, as a surrogate marker for dysphagia presence and severity), penetration aspiration scale, and the presence of moderate-to-severe pharyngeal residues were collected from the clinical records. Univariate and multivariate ordinal and logistic regression analyses were performed to analyse if total CSA of swallowing muscles and SMI were associated with FEES parameters. RESULTS: The final study population consisted of 137 patients, 59 were female (43.1%), median age was 74 years (interquartile range 62-83), median baseline National Institutes of Health Stroke Scale score was 12 (interquartile range 7-16), 16 patients had a vertebrobasilar occlusion (11.7%), and successful recanalization was achieved in 127 patients (92.7%). Both total CSA of swallowing muscles and SMI were significantly correlated with age (rho = -0.391, P < 0.001 and rho = -0.525, P < 0.001, respectively). Total CSA of the swallowing muscles was independently associated with FOIS (common adjusted odds ratio = 1.08, 95% confidence interval = 1.01-1.16, P = 0.029), and with the presence of moderate-to-severe pharyngeal residues for puree consistencies (adjusted odds ratio = 0.90, 95% confidence interval = 0.81-0.99, P = 0.036). We found no independent association of SMI with any of the FEES parameters. CONCLUSIONS: Baseline swallowing muscle mass contributes to the pathophysiology of post-stroke dysphagia. Decreasing swallowing muscle mass is independently associated with increasing severity of early post-stroke dysphagia and with increased likelihood of moderate-to-severe pharyngeal residues.

Bacterial Contamination of Syringes and Fluids in Diagnostic and Interventional Neuroangiography.

(1) Background: Bacterial contamination has been shown to occur during angiographies, although data on its frequency and relevance are sparse. Our aim was to evaluate the incidence of bacterial contamination of syringes used under sterile conditions during neuroangiographies. We sought to differentiate between contamination of the outside of the syringes and the inside and to detect the frequency, extent and germ spectrum of bacterial contamination. (2) Methods: We prospectively collected 600 samples from 100 neuroangiographies. Per angiography, fluid samples from the three routinely used syringes as well as the syringes themselves were analyzed. We analyzed the frequency and extent of contamination and determined the germ spectrum. (3) Results: The majority of samples (56.9%) were contaminated. There was no angiography that showed no contamination (0%). The outer surfaces of the syringes were contaminated significantly more frequently and to a higher extent than the inner surfaces. Both the frequency and extent of contamination of the samples increased with longer duration of angiographic procedures. Most of the bacterial species were environmental or skin germs (87.7%). (4) Conclusions: Bacterial contamination is a frequent finding during neuroangiographies, although its clinical significance is believed to be small. Bacterial contamination increases with longer duration of angiographic procedures.

Nimodipine as Vasodilator in Guide Catheter Flush to Prevent Vasospasm During Endovascular Stroke Treatment.

PURPOSE: The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate the effect of adding nimodipine to the guiding catheter flush (GCF) to prevent vasospasm during EVT. METHODS: This is a single-center retrospective analysis including patients with EVT (stent-retriever and/or distal aspiration) treated for anterior or posterior circulation intracranial vessel occlusion from January 2018 to June 2023. Exclusion criteria were intracranial or extracranial stenosis, intra-arterial alteplase, patient age over 80 years. Study groups were patients with (nimo+) and without (nimo-) nimodipine in the GCF. They were compared for occurrence of vasospasm as primary endpoint and clinical outcome in univariate analysis. RESULTS: 477 patients were included in the analysis (nimo+ n = 94 vs. nimo- n = 383). Nimo+ patients experienced less vasospasm during EVT (e.g. vasospasm in target vessel n (%): nimo- = 113 (29.6) vs. nimo+ = 9 (9.6), p < 0.001; extracranial vasospasm, n (%): nimo- = 68 (17.8) vs. nimo+ = 7 (7.4), p = 0.017). Patients of the two study groups had a comparable clinical outcome (90 day mRS, median (IQR): 3 (1-6) for both groups, p = 0.896). In general, patients with anterior circulation target vessel occlusion (TVO) experienced more vasospasm (anterior circ. TVO 38.7% vs. posterior circ. 7.5%, p = 0.006). CONCLUSION: Prophylactic adding of nimodipine reduces the risk of vasospasm during EVT without affecting the clinical outcome. Patients with anterior circulation TVO experienced more vasospasm compared to posterior circulation TVO.

Impact of Vaccination Status on Outcome of Patients With COVID-19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

BACKGROUND: Data on impact of COVID-19 vaccination and outcomes of patients with COVID-19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience. METHODS AND RESULTS: This was a retrospective analysis of patients with COVID-19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID-19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients; P=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (P=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (P=0.957). However, acute COVID-19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007-1.417]; P=0.041). CONCLUSIONS: Our study demonstrated no impact of COVID-19 vaccination on angiographic or clinical outcome of COVID-19-positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID-19 was confirmed.

Safety and efficacy of coated flow diverters in the treatment of ruptured intracranial aneurysms: a retrospective multicenter study.

BACKGROUND: This multicenter study evaluated the safety and efficacy of coated flow diverters (cFDs) for the treatment of ruptured intracranial aneurysms. METHODS: Consecutive patients treated with different cFDs for ruptured aneurysms under tirofiban at eight neurovascular centers between 2016 and 2023 were retrospectively analyzed. The majority of patients were loaded with dual antiplatelet therapy after the treatment. Aneurysm occlusion was determined using the O'Kelly-Marotta (OKM) grading scale. Primary outcome measures were major procedural complications and aneurysmal rebleeding during hospitalization. RESULTS: The study included 60 aneurysms (posterior circulation: 28 (47%)) with a mean size of 5.8±4.7 mm. Aneurysm morphology was saccular in 28 (47%), blister-like in 12 (20%), dissecting in 13 (22%), and fusiform in 7 (12%). Technical success was 100% with a mean of 1.1 cFDs implanted per aneurysm. Adjunctive coiling was performed in 11 (18%) aneurysms. Immediate contrast retention was observed in 45 (75%) aneurysms. There was 1 (2%) major procedural complication (a major stroke, eventually leading to death) and no aneurysmal rebleeding. A good outcome (modified Rankin Scale 0-2) was achieved in 40 (67%) patients. At a mean follow-up of 6 months, 27/34 (79%) aneurysms were completely occluded (OKM D), 3/34 (9%) had an entry remnant (OKM C), and 4/34 (12%) had residual filling (OKM A or B). There was 1 (3%) severe in-stent stenosis during follow-up that was treated with balloon angioplasty. CONCLUSIONS: Treatment of ruptured aneurysms with cFDs was reasonably safe and efficient and thus represents a valid treatment option, especially for complex cases.

Evaluating the accuracy of cerebrovascular computational fluid dynamics modeling through time-resolved experimental validation.

Accurate modeling of cerebral hemodynamics is crucial for better understanding the hemodynamics of stroke, for which computational fluid dynamics (CFD) modeling is a viable tool to obtain information. However, a comprehensive study on the accuracy of cerebrovascular CFD models including both transient arterial pressures and flows does not exist. This study systematically assessed the accuracy of different outlet boundary conditions (BCs) comparing CFD modeling and an in-vitro experiment. The experimental setup consisted of an anatomical cerebrovascular phantom and high-resolution flow and pressure data acquisition. The CFD model of the same cerebrovascular geometry comprised five sets of stationary and transient BCs including established techniques and a novel BC, the phase modulation approach. The experiment produced physiological hemodynamics consistent with reported clinical results for total cerebral blood flow, inlet pressure, flow distribution, and flow pulsatility indices (PI). The in-silico model instead yielded time-dependent deviations between 19-66% for flows and 6-26% for pressures. For cerebrovascular CFD modeling, it is recommended to avoid stationary outlet pressure BCs, which caused the highest deviations. The Windkessel and the phase modulation BCs provided realistic flow PI values and cerebrovascular pressures, respectively. However, this study shows that the accuracy of current cerebrovascular CFD models is limited.

Early flexible endoscopic evaluation of swallowing after mechanical thrombectomy in stroke patients.

OBJECTIVE: The aims of the study were to (1) characterize the findings of flexible endoscopic evaluation of swallowing (FEES) in stroke patients undergoing mechanical thrombectomy (MT); (2) analyse the screening performance of the Standardized Swallowing Assessment (SSA); and (3) study the impact of FEES-defined dysphagia on 3-month outcomes. METHODS: This single-centre study was based on a local registry of consecutive acute ischaemic stroke patients undergoing MT during a 1-year period. Patients received FEES within 5 days of admission regardless of the result of dysphagia screening. We compared baseline demographic and clinical characteristics of patients with and without FEES-defined dysphagia. We collected 3-month modified Rankin Scale (mRS) and individual index values of the European Quality of Life 5 Dimensions (EQ-5D-iv). Using univariable and multivariable regression analyses we predicted 3-month outcomes for presence of dysphagia and for FEES-defined dysphagia severity. RESULTS: We included 137 patients with a median age of 74 years, 43.1% were female, median NIHSS was 12 and successful recanalization was achieved in 92.7%. Stroke-associated pneumonia occurred in 8% of patients. FEES-defined dysphagia occurred in 81% of patients. Sensitivity of the SSA as a dysphagia screening was 67%. Presence of dysphagia and increasing severity of dysphagia were independently associated with increasing 3-month mRS score. Increasing dysphagia severity dysphagia was independently associated with lower EQ-5D-iv. INTERPRETATION: Early FEES-defined dysphagia occurs in four in every five patients undergoing MT. SSA has a suboptimal dysphagia screening performance. Presence of dysphagia and increasing dysphagia severity predict worse functional outcome and worse health-related quality-of-life.

Comparison of artery diameters in the Aachen minipig serving as a human intracranial in vivo model.

Minipigs are used as in vivo endovascular models, particularly in stroke and aneurysm research. However, detailed knowledge of the diameters of forelimb arteries that are commonly used as surrogates for human brain-supplying arteries are lacking. This study aimed to determine the diameters of forelimb and neck arteries in Aachen minipigs and to compare those to the diameters of human cerebral brain-supplying arteries in order to assess the validity of the Aachen minipig as a human intracranial in vivo model. We measured the diameters in the external carotid artery and eight different branches of the subclavian artery in 12 Aachen minipigs using angiographic imaging. Analysed arteries comprised the external carotid artery, axillary artery, brachial artery, subscapular artery first segment, subscapular artery second segment, external thoracic artery, caudal circumflex humeral artery, suprascapular artery and thoracodorsal artery. We compared these diameters to diameters of the following human brain-supplying arteries: terminal internal carotid artery (carotid-T and petrous segment), M1 segment of the middle cerebral artery, M2 segments of the middle cerebral artery, anterior cerebral artery, vertebral artery and basilar artery. Median diameters of porcine forelimb arteries ranged from 1.8 to 4.9 mm, and human brain supplying arteries ranged in diameter from 1.4 to 4.3 mm. Depending on the intended use, this allows porcine forelimb arteries to be selected which are statistically comparable to human brain-supplying vessels. In conclusion, we identified several equivalent arteries of the porcine subclavian branches that are comparable to human brain-supplying arteries. This may help to validate the minipig as a suitable in vivo model for neurovascular experiments.

Factors associated with the laterality of Cardio-Embolic stroke.

OBJECTIVE: Understanding the lateralization factors, including the anatomic and hemodynamic mechanisms, is essential for diagnosing cardio-embolic stroke. This study aims to investigate the elements, for the first time together, that could affect the laterality of stroke. METHODS: We performed a monocentric retrospective case-control study based on prospective registries of acute ischemic stroke patients in the comprehensive stroke center of the RWTH University hospital of Aachen for three years (June 2018-June 2021). We enrolled 222 patients with cardioembolic stroke (136 left stroke and 86 right stroke) admitted for first-ever acute ischemic stroke with unilateral large vessel occlusion of the anterior circulation. The peak systolic velocity (PSV) asymmetry of middle cerebral artery (MCA) was assessed by doppler as well as internal carotid artery (ICA) angle, aortic arch (AA) branching pattern and anatomy were assessed by CT-Angiography. RESULTS: We found that the increasing left ICA angle (p = 0.047), presence of bovine type AA anatomy (p = 0.041) as well as slow PSV of the right MCA with a value of >15% than left (p = 0.005) were the predictors for left stroke lateralization, while the latter was an independent predictor for the left stroke (OR=3.341 [1.415-7.887]). Inter-Rater Reliability ranged from moderate to perfect agreement. CONCLUSION: The predictors for left stroke lateralization include the higher values of left ICA angle, presence of the bovine type AA and the slow right MCA PSV.

The relationship between neurogenic dysphagia, stroke-associated pneumonia and functional outcome in a cohort of ischemic stroke patients treated with mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is an established treatment approach in acute ischemic stroke patients with large vessel occlusion (LVO). Recent studies suggest that the prevalence of dysphagia and pneumonia risk is increased in this patient population. The aim of this study was to systematically evaluate the prevalence, predictors, and influence of neurogenic dysphagia for 3-month outcome in a large population of patients receiving MT and to elucidate the relationship between dysphagia, stroke-associated pneumonia (SAP) and medium-term functional outcome. MATERIALS AND METHODS: Data of a prospective collected registry of patients with LVO and MT between 2016 and 2019 were analyzed retrospectively. Binary logistic regression was carried out to determine predictors for dysphagia and 3-month outcome as measured by the modified Rankin Scale, respectively. A mediation analysis was performed to investigate the mediating influence of intercurrent SAP. RESULTS: A total of 567 patients were included in the study. Mean age was 73.4 years, 47.8% of the patients were female, and median NIHSS was 15.0. The prevalence of dysphagia was 75.1% and 23.3% of all patients developed SAP. In the regression analysis, dysphagia was one of the main independent predictors for poor functional outcome at 3 months. The mediator analysis revealed that the effect of dysphagia on the functional outcome at 3 months was not mediated by the occurrence of SAP. DISCUSSION: The prevalence of dysphagia is high and exerts both negative short- and medium-term effects on patients with large vessel occlusion who undergo MT.

Frequency and Pattern of MRI Diffusion Restrictions after Diagnostic Catheter Neuroangiography.

(1) Background: We investigated the frequency, location, and lesion size of diffusion restrictions (DR) in magnetic resonance imaging (MRI) of asymptomatic patients after diagnostic angiography and assessed risk factors for their occurrence. (2) Methods: We analyzed diffusion-weighted images (DWI) of 344 patients undergoing diagnostic angiographies in a neuroradiologic center. Only asymptomatic patients who received a magnetic resonance imaging (MRI) examination within seven days after the angiography were included. (3) Results: Asymptomatic infarcts on DWI were identified in 17% of the cases after diagnostic angiography. In these 59 patients, a total of 167 lesions were noted. The diameter of the lesions was 1-5 mm in 128 lesions, and 5-10 mm in 39 cases. Dot-shaped diffusion restrictions were found most frequently (n = 163, 97.6%). None of the patients had neurological deficits during or after angiography. Significant correlations were found between the occurrence of lesions and patient age (p < 0.001), history of atherosclerosis (p = 0.014), cerebral infarction (p = 0.026), or coronary heart disease/heart attack (p = 0.027); and the amount of contrast medium used (p = 0.047) and fluoroscopy time (p = 0.033). (4) Conclusions: With an incidence of 17%, we observed a comparatively high risk for asymptomatic cerebral ischemia after diagnostic neuroangiography. Further measures to reduce the risk of silent embolic infarcts and improve the safety of neuroangiography are warranted.

Spectrum of Complications and Complication Rates After Diagnostic Catheter Angiography in Neuroradiology.

PURPOSE: To retrospectively evaluate the total complication rates and type of complications after diagnostic cerebral and spinal catheter angiography. METHODS: Data from 2340 patients undergoing diagnostic angiography over a period of 10 years in a neuroradiologic center were retrospectively evaluated. Local, systemic, neurological, and technical complications were analyzed. RESULTS: A total of 75 clinically noted complications occurred. The risk for clinical complications was increased when the angiography was performed under emergency conditions (p = 0.009). The most common complication was groin hematoma (1.32%). Neurological complications occurred in 0.68% of patients, of which 0.13% were stroke with permanent disability. Technical complications without noticeable clinical symptoms of the patients occurred in 2.35% of the angiographic procedures. Deaths caused by angiography did not occur. CONCLUSION: There is a definite risk for complications after diagnostic angiography. Although a very broad spectrum of complications was considered, complications in the individual subgroups showed a low incidence.

Hyperacute Perfusion Imaging Before Pediatric Thrombectomy: Analysis of the Save ChildS Study.

BACKGROUND AND OBJECTIVES: Perfusion imaging can identify adult patients with salvageable brain tissue who would benefit from thrombectomy in later time windows. The feasibility of obtaining hyperacute perfusion sequences in pediatric stroke is unknown. The aim of this study was to determine whether contrast perfusion imaging delayed time to treatment and to assess perfusion profiles in children with large vessel occlusion stroke. METHODS: The Save ChildS retrospective cohort study (January 2000-December 2018) enrolled children (1 month-18 years) with stroke who underwent thrombectomy from 27 European and U.S. stroke centers. This secondary analysis included patients with anterior circulation occlusion and available imaging for direct review by the neuroimaging core laboratory. Between-group comparisons were performed using the Wilcoxon rank-sum exact test for continuous variables or Fisher exact test for binary variables. Given the small number of patients, evaluation of perfusion imaging parameters was performed descriptively only. RESULTS: Of 33 patients with available neuroimaging, 15 (45.4%) underwent perfusion (CT perfusion n = 6; MR perfusion n = 9); all were technically adequate. The median time from onset to recanalization did not differ between groups {4 hours (interquartile range [IQR] 4-7.5) perfusion+; 3.4 hours (IQR 2.5-6.5) perfusion-, p = 0.158}. Target mismatch criteria were met by 10/15 (66.7%) patients and did not correlate with reperfusion status or functional outcome. The hypoperfusion intensity ratio (HIR) was favorable in 11/15 patients and correlated with older age but not NIHSS, time to recanalization, or stroke etiology. Favorable HIR was associated with better functional outcome at 6 months (Pediatric Stroke Outcome Measure 1.0 [IQR 0.5-2.0] vs 2.0 [1.5-3.0], p = 0.026) and modified Rankin Scale 1.0 [0-1] vs 2.0 [1.5-3.5], p = 0.048) in this small sample. DISCUSSION: Automated perfusion imaging is feasible to obtain acutely in children and does not delay time to recanalization. Larger prospective studies are needed to determine biomarkers of favorable outcome in pediatric ischemic stroke and to establish core and penumbral thresholds in children.

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS: SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS: Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION: Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03192332.

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Meniscus Sign in Patients with Anterior Circulation Large Vessel Occlusion Stroke does not Predict Outcome.

PURPOSE: The angiographic appearance of the occlusion site was suggested to influence outcomes of stroke patients with large vessel occlusion (LVO) who undergo endovascular treatment (EVT). We aimed to study the impact of the meniscus sign (MS) on outcomes of stroke patients with anterior circulation LVO. METHODS: Based on two prospective registries of acute ischemic stroke, we selected patients with carotid­T, M1 or M2 occlusion who underwent EVT. Clinical characteristics and outcomes were collected from the registries or from individual records. Two independent observers blinded to outcomes assessed the presence of MS in digital subtraction angiography before thrombectomy. Angiographic and clinical outcomes of patients with and without MS were compared. RESULTS: We included 903 patients, with median age of 78 years, 59.8% were male, median baseline NIHSS was 14 and 39.5% received intravenous thrombolysis. Patients with MS (n = 170, 18.8%) were more frequently female, presented with higher NIHSS scores and more frequently underwent intravenous thrombolysis. Presence of MS was significantly associated with cardioembolic etiology. Successful reperfusion, number of passes, first pass effect, procedural time, symptomatic intracerebral hemorrhage, in-hospital mortality and favorable 3­month functional outcome were similar in the groups of patients with and without MS. In the multivariable analyses, MS was not associated with successful reperfusion (odds ratio, OR = 1.08, 95% confidence interval, CI = 0.76-1.55), first pass effect (OR = 0.96, 95%CI = 0.48-1.92) or favorable 3­month outcome (OR = 1.40, 95%CI = 0.88-2.24). CONCLUSION: The presence of MS in acute ischemic stroke patients with anterior circulation large vessel occlusion who undergo EVT does not appear to influence angiographic or clinical outcomes.

Flow control in the middle cerebral artery during thrombectomy: the effect of anatomy, catheter size and tip location.

BACKGROUND: Catheter size, location and circle of Willis anatomy impact the flow conditions during interventional stroke therapy. The aim of the study was to systematically investigate the influence of these factors on flow control in the middle cerebral artery by means of a computational model based on 100 patients with stroke who received endovascular treatment. METHODS: The dimensions of the cervical and intracranial cerebral arteries of 100 patients who received endovascular mechanical thrombectomy for acute ischemic stroke were measured and a three-dimensional model of the circle of Willis was created based on these data. Flow control in the middle cerebral artery with variations in catheter size, catheter location and configurations of collateral vessels was determined using a computational model. A total of 48 scenarios were analyzed. RESULTS: Flow reversal with a distal aspiration catheter alone was not possible in the internal carotid artery and only sometimes possible in the middle cerebral artery (14 of 48 cases). The Catalyst 7 catheter was more often successful in achieving flow reversal than Catalyst 5 or 6 catheters (p<0.001). In a full circle of Willis anatomy, flow reversal was almost never possible. The absence of one or more communicating arteries significantly influenced flow direction compared with the full anatomy with all communicating arteries present (p=0.028). CONCLUSION: Choosing the biggest possible aspiration catheter and locating it in the middle cerebral artery significantly increases the chances of successful flow control. Flow through the collaterals may impair the flow, and circle of Willis anatomy should be considered during aspiration thrombectomy.