Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

A sex-specific association of leukocyte telomere length with thigh muscle mass.

OBJECTIVES: Telomeres are DNA-protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored. METHODS: We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour. RESULTS: In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females. CONCLUSIONS: In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women.

Influence of safety glasses, body height and magnification on the occupational eye lens dose during pelvic vascular interventions: a phantom study.

OBJECTIVE: By simulating a fluoroscopic-guided vascular intervention, two differently designed radiation safety glasses were compared. The impacts of changing viewing directions and body heights on the eye lens dose were evaluated. Additionally, the effect of variable magnification levels on the arising scattered radiation was determined. METHODS: A phantom head, replacing the operator's head, was positioned at different heights and rotated in steps of 20° in the horizontal plane. Thermoluminescent dosimeters (TLD), placed in the left orbit of the phantom, detected eye lens doses under protected and completely exposed conditions. In a second step, radiation dose values with increasing magnification levels were detected by RaySafe i3 dosimeters. RESULTS: Changing eye levels and head rotations resulted in a wide range of dose reduction factors (DRF) from 1.1 to 8.5. Increasing the vertical distance between the scattering body and the protective eyewear, DRFs markedly decreased for both glasses. Significant differences between protection glasses were observed. Increasing magnification with consecutively decreasing FOV size variably reduced the dose exposure to the eye lens between 47 and 83%, respectively. CONCLUSION: The safety glasses in the study effectively reduced the dose exposure to the eye lens. However, the extent of the protective effect was significant depending on eye levels and head rotations. This may lead to a false sense of safety for the medical staff. In addition, the application of magnification reduced the quantity of scattering dose significantly. To ensure safe working in the Cath-lab, additional use of protective equipment and the differences in design of protective eyewear should be considered. KEY POINTS: • Eye lens dose changes with physical size of the interventionist and viewing direction. • The use of magnification during fluoroscopic-guided interventions reduces scattered radiation.

FDA-approved deep learning software application versus radiologists with different levels of expertise: detection of intracranial hemorrhage in a retrospective single-center study.

PURPOSE: To assess an FDA-approved and CE-certified deep learning (DL) software application compared to the performance of human radiologists in detecting intracranial hemorrhages (ICH). METHODS: Within a 20-week trial from January to May 2020, 2210 adult non-contrast head CT scans were performed in a single center and automatically analyzed by an artificial intelligence (AI) solution with workflow integration. After excluding 22 scans due to severe motion artifacts, images were retrospectively assessed for the presence of ICHs by a second-year resident and a certified radiologist under simulated time pressure. Disagreements were resolved by a subspecialized neuroradiologist serving as the reference standard. We calculated interrater agreement and diagnostic performance parameters, including the Breslow-Day and Cochran-Mantel-Haenszel tests. RESULTS: An ICH was present in 214 out of 2188 scans. The interrater agreement between the resident and the certified radiologist was very high (κ = 0.89) and even higher (κ = 0.93) between the resident and the reference standard. The software has delivered 64 false-positive and 68 false-negative results giving an overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68.2%, 96.8%, 69.5%, 96.6%, and 94.0%, respectively. Corresponding values for the resident were 94.9%, 99.2%, 93.1%, 99.4%, and 98.8%. The accuracy of the DL application was inferior (p < 0.001) to that of both the resident and the certified neuroradiologist. CONCLUSION: A resident under time pressure outperformed an FDA-approved DL program in detecting ICH in CT scans. Our results underline the importance of thoughtful workflow integration and post-approval validation of AI applications in various clinical environments.

Automated MRI perfusion-diffusion mismatch estimation may be significantly different in individual patients when using different software packages.

OBJECTIVE: To compare two established software applications in terms of apparent diffusion coefficient (ADC) lesion volumes, volume of critically hypoperfused brain tissue, and calculated volumes of perfusion-diffusion mismatch in brain MRI of patients with acute ischemic stroke. METHODS: Brain MRI examinations of 81 patients with acute stroke due to large vessel occlusion of the anterior circulation were analyzed. The volume of hypoperfused brain tissue, ADC volume, and the volume of perfusion-diffusion mismatch were calculated automatically with two different software packages. The calculated parameters were compared quantitatively using formal statistics. RESULTS: Significant difference was found for the volume of hypoperfused tissue (median 91.0 ml vs. 102.2 ml; p < 0.05) and the ADC volume (median 30.0 ml vs. 23.9 ml; p < 0.05) between different software packages. The volume of the perfusion-diffusion mismatch differed significantly (median 47.0 ml vs. 67.2 ml; p < 0.05). Evaluation of the results on a single-subject basis revealed a mean absolute difference of 20.5 ml for hypoperfused tissue, 10.8 ml for ADC volumes, and 27.6 ml for mismatch volumes, respectively. Application of the DEFUSE 3 threshold of 70 ml infarction core would have resulted in dissenting treatment decisions in 6/81 (7.4%) patients. CONCLUSION: Volume segmentation in different software products may lead to significantly different results in the individual patient and may thus seriously influence the decision for or against mechanical thrombectomy. KEY POINTS: • Automated calculation of MRI perfusion-diffusion mismatch helps clinicians to apply inclusion and exclusion criteria derived from randomized trials. • Infarct volume segmentation plays a crucial role and lead to significantly different result for different computer programs. • Perfusion-diffusion mismatch estimation from different computer programs may influence the decision for or against mechanical thrombectomy.

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, P=0.316). MPV levels did also not change from baseline to ISR detection (P=0.310) and were not associated with recurrent stroke or vascular events (P>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.

Nigral iron deposition in common tremor disorders.

OBJECTIVE: We investigated R2* relaxation rates as a marker of iron content in the substantia nigra in patients with common tremor disorders and explored their diagnostic properties. METHODS: Mean nigral R2* rates were measured in 40 patients with tremor-dominant Parkinson's disease (PD), 15 with tremor in dystonia, 25 with essential tremor, and 25 healthy controls. RESULTS: Tremor-dominant PD patients had significantly higher nigral R2* values (34.1 ± 5.7) than those with tremor in dystonia (30.0 ± 3.9), essential tremor (30.6 ± 4.8), and controls (30.0 ± 2.8). An R2* threshold of 31.15 separated tremor-dominant PD from controls with a sensitivity and specificity of 67.5% and 72%. The sensitivity and specificity for discrimination between PD and non-PD tremor patients was 67.5% and 60%. CONCLUSION: Iron content in the substantia nigra is significantly higher in tremor-dominant PD than in tremor in dystonia, essential tremor, and controls. Because of the considerable overlap, nigral R2* cannot be suggested as a useful diagnostic tool. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Volume Computed Tomography Perfusion Imaging: Evaluation of the Significance in Oncologic Follow-up of Metastasizing Renal Cell Carcinoma in the Early Period of Targeted Therapy - Preliminary Results.

INTRODUCTION: The aim of this study was to assess the significance of volume computed tomography perfusion imaging of metastasizing renal cell carcinoma (mRCC) in the early period after the initiation of targeted therapy. METHODS: Blood flow (BF), blood volume, and clearance (CL) were calculated in 10 patients with histologically verified mRCC before and 1 month after initiation of targeted therapy using compartmental analysis algorithms. In addition, the longest diameter of tumor was measured for both time points and compared. Correlation test was performed between perfusion parameters and size changes with time to progression (TTP). RESULTS: Blood flow and CL were significantly lower after therapy initiation, whereas blood volume and the long diameter remained unchanged. Median values before and after 4 weeks of therapy were 144.2 versus 99.4 mL/min/100 mL for BF (P = 0.009) and 115.5 versus 46.8 mL/min/100 mL for CL (P = 0.007). Changes in BF and CL showed very strong negative correlation with TTP (r = -0.838, P = 0.009 and r = -0.826, P = 0.011, respectively). CONCLUSIONS: Our preliminary study results indicate that volume computed tomography perfusion may assess targeted therapy response of mRCC earlier than the currently used Response Evaluation Criteria in Solid Tumors. In addition, changes in BF and CL may be a promising parameter for prediction of TTP.

Abnormal Blood Flow on Transcranial Duplex Sonography Predicts Poor Outcome After Stroke Thrombectomy.

Background and Purpose- Hemodynamic changes following mechanical thrombectomy for large vessel occlusion stroke could be associated with complications and might affect prognosis. We investigated postinterventional middle cerebral artery blood flow on transcranial duplex sonography (TCD) and its prognostic value for anterior large vessel occlusion stroke patients. Methods- We identified all ischemic stroke patients who had undergone mechanical thrombectomy for anterior circulation large vessel occlusion from 2010 onwards. Postinterventional middle cerebral artery flow was graded according to the sonographic Thrombolysis in Brain Ischemia score and related to patient outcome stratified by the angiographic Thrombolysis in Cerebral Infarction reperfusion status. Results- Of 215 large vessel occlusion stroke patients, 193 patients (90%) showed successful angiographic recanalization (Thrombolysis in Cerebral Infarction grade 2b-3). Of those, 69 (36%) patients had abnormal sonographic middle cerebral artery blood flow (Thrombolysis in Brain Ischemia grade 0-4) within 72 hours after mechanical thrombectomy, which was an independent predictor for poor 90-day outcome. Conclusions- TCD indicates abnormal middle cerebral artery hemodynamics in a substantial proportion of patients with angiographically defined successful mechanical thrombectomy of the anterior cerebral circulation. Such changes are associated with poor short-term outcome.

Periventricular lesions correlate with cortical thinning in multiple sclerosis.

OBJECTIVE: It has been suggested recently that cortical pathology in multiple sclerosis (MS) may, at least partly, be caused by factors in cerebrospinal fluid (CSF). We thus hypothesized that MS-related tissue changes in compartments close to the CSF, such as periventricular lesions, might correlate with cortical pathology. METHODS: We investigated a cohort of 160 patients, comprising 91 with a clinically isolated syndrome (CIS) and 69 with relapsing-remitting MS (RRMS; mean age: CIS: 31.4 ± 9.0; RRMS: 33.0 ± 8.7 years; mean disease duration: CIS: 7.2 ± 15 months; RRMS: 8.0 ± 6.5 years, Expanded Disability Status Scale (median, min-max): CIS: 1, 0-3.5; RRMS: 1.25, 0-4) with 3.0T magnetic resonance imaging. MS lesions were segmented semiautomatically on fluid-attenuated inversion recovery images. To quantify periventricular lesion load (PV-LL), we generated ventricle masks and dilated them by a voxel factor of 3. Lesions within the dilated ventricle margin were classified as periventricular. Cortical thinning was assessed by cortical mean thickness (CMT) and compared to data from 58 healthy controls (HCs; mean age: 29.1 ± 7.4 years). RESULTS: Compared to HC, CIS and (even more so) RRMS patients demonstrated significantly reduced CMT. Even after controlling for ventricular volume and total lesion load, increased periventricular lesion occupancy (percentage of PV-LL) significantly correlated with decreased CMT in RRMS (r = -0.295; p = 0.015), but not in CIS (r = 0.032; p = 0.768) patients. INTERPRETATION: The correlation between increased periventricular lesion burden and decreased CMT indicative of subpial cortical pathology supports the concept that common CSF-mediated factors might play a role in the accumulation of damage to gray and white matter in MS.

Mechanical recanalization in basilar artery occlusion: the ENDOSTROKE study.

OBJECTIVE: A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion. METHODS: ENDOSTROKE is an investigator-initiated multicenter registry for patients undergoing EVT. This analysis includes 148 consecutive patients with BA occlusion, with 59% having received intravenous thrombolysis prior to EVT. Recanalization (defined as Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and collateral status (using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology collateral grading system) were assessed by a blinded core laboratory. Good (moderate) outcome was defined as a modified Rankin Scale score of 0 to 2 (0-3) assessed after at least 3 months (median time to follow-up = 120 days). RESULTS: Thirty-four percent had good and 42% had moderate clinical outcome; mortality was 35%. TICI 2b-3 recanalization was achieved by 79%. Age, hypertension, National Institutes of Health Stroke Scale scores, collateral status, and the use of magnetic resonance imaging prior to EVT predicted clinical outcome, the latter 3 remaining independent predictors in multivariate analysis. Independent predictors of recanalization were better collateral status and the use of a stent retriever. However, recanalization did not significantly predict clinical outcome. INTERPRETATION: Beside initial stroke severity, the collateral status predicts clinical outcome and recanalization in BA occlusion. Our data suggest that the use of a stent retriever is associated with high recanalization rates, but recanalization on its own does not predict outcome. The role of other modifiable factors, including the choice of pretreatment imaging modality and time issues, warrants further investigation.

In vivo cardiovascular magnetic resonance of 2D vessel wall diffusion anisotropy in carotid arteries.

BACKGROUND: Diffusion weighted (DW) cardiovascular magnetic resonance (CMR) has shown great potential to discriminate between healthy and diseased vessel tissue by evaluating the apparent diffusion coefficient (ADC) along the arterial axis. Recently, ex vivo studies on porcine arteries utilizing diffusion tensor imaging (DTI) revealed a circumferential fiber orientation rather than an organization in axial direction, suggesting dominant diffusion perpendicular to the slice direction. In the present study, we propose a method to access tangential and radial diffusion of carotids in vivo by utilizing a pulse sequence that enables high resolution DW imaging in combination with a two-dimensional (2D) diffusion gradient direction sampling scheme perpendicular to the longitudinal axis of the artery. METHODS: High resolution DTI of 12 healthy male volunteers (age: 25-60 years) was performed on one selected axial slice using a read-out segmented EPI (rs-EPI) sequence on a 3T MR scanner. RESULTS: It was found consistently for all 12 volunteers, that the tangential component as the principle direction of diffusion. Mean vessel wall fractional anisotropy (FA) values ranged from 0.7 for the youngest to 0.56 for the oldest participant. Linear regression analysis between the FA values and volunteers age revealed a highly significant (P < 0.01) linear relationship with an adjusted R2 of 0.52. In addition, a linear trend (P < 0.1) could be observed between radial diffusivity (RD) and age. CONCLUSION: These results point to FA being a sensitive parameter able to capture changes in the vascular architecture with age. In detail, the data demonstrate a decrease in FA with advancing age indicating possible alterations of tissue microstructural integrity. Moreover, analyzing 2D diffusion tensor directions is sufficient and applicable in a clinical setup concerning the overall scan time.

Cortical Superficial Siderosis and Risk of Bleeding after Thrombolysis for Ischemic Stroke.

BACKGROUND: Cortical superficial siderosis (CSS) is a neuroimaging marker of cerebral amyloid angiopathy and has been associated with a high risk for early subsequent major intracranial hemorrhage (ICH). Therefore, many experts recommend withholding of antithrombotic medication to patients with CSS. In this study, we sought to investigate the prevalence of CSS and the associated risk of ICH in the setting of intravenous thrombolysis (IVT) for ischemic stroke. METHODS: We retrospectively searched the medical documentation system of our primary and tertiary care university clinic for all patients with ischemic stroke that received IVT from 2009 to December 2014. All available imaging data were reviewed in a standardized manner and blinded to any clinical data for the presence of CSS and ICH. CSS was defined as linear signal loss along the cerebral cortex on gradient echo T2*-weighted sequences. A stroke neurologist, who was blinded to the neuroimaging data, extracted the corresponding clinical data including follow-up information. RESULTS: We identified 298 patients that received IVT and had undergone brain MRI (mean age 67.6 ± 12.6 years, 59.4% male). Cerebral MRI was performed in 116 patients (38.9%) before and in 182 patients (61.1%) after IVT (median time from stroke symptom onset to MRI: 1 day; range 0-7 days). Only 3 patients (2 females and 1 male aged 90, 76 and 73 years, respectively) had CSS (1%). All of them had a middle cerebral artery (MCA) stroke with a corresponding vessel occlusion. The 76-year-old female patient had extensive CSS and numerous cerebral microbleeds and received another IVT treatment for recurrent MCA stroke 8 months after the first event. After both IVTs, she had clinically asymptomatic small ICH outside the ischemic infarct and distant from CSS. The 2 other patients had only mild to moderate CSS and did not experience any ICH on postthrombolytic imaging. CONCLUSIONS: The prevalence of CSS in a clinical cohort of stroke patients that received IVT was low and thus does not appear to pose a substantial risk for symptomatic ICH although this may occur in individual patients. However, such analysis also needs to be extended to the very old stroke patients in whom IVT is increasingly used.

Wall Enhancement of Coiled Intracranial Aneurysms Is Associated with Aneurysm Recanalization: A Cross-Sectional Study.

BACKGROUND AND PURPOSE: Wall enhancement of untreated intracranial aneurysms on MR imaging is thought to predict aneurysm instability. Wall enhancement or enhancement of the aneurysm cavity in coiled intracranial aneurysms is discussed controversially in the literature regarding potential healing mechanisms or adverse inflammatory reactions. Our aim was to compare the occurrence of aneurysm wall enhancement and cavity enhancement between completely occluded intracranial aneurysms and recanalized aneurysms after initially complete coil embolization. MATERIALS AND METHODS: In this single-center cross-sectional study, we evaluated intracranial aneurysms after successful coil embolization for aneurysm recanalization, wall enhancement, and cavity enhancement with 3T MR imaging. We then compared the incidence of wall enhancement and cavity enhancement of completely occluded aneurysms with aneurysms with recanalization using the χ2 test and performed a multivariate linear regression analysis with recanalization size as an independent variable. RESULTS: We evaluated 59 patients (mean age, 54.7 [SD, 12.4] years; 48 women) with 60 intracranial aneurysms and found a significantly higher incidence of wall enhancement in coiled aneurysms with recanalization (n=38) compared with completely occluded aneurysms (n = 22, P = .036). In addition, there was a significantly higher incidence of wall enhancement in aneurysms with recanalization of >3 mm (P = .003). In a multivariate linear regression analysis, wall enhancement (P = .010) and an increase of overall aneurysm size after embolization (P < .001) were significant predictors of recanalization size (corrected R 2= 0.430, CI 95%). CONCLUSIONS: The incidence of aneurysm wall enhancement is increased in coiled intracranial aneurysms with recanalization and is associated with recanalization size.

White matter integrity and functional connectivity of the default mode network in acute stroke are associated with cognitive outcome three months post-stroke.

BACKGROUND: Knowledge about factors that are associated with post-stroke cognitive outcome is important to identify patients with high risk for impairment. We therefore investigated the associations of white matter integrity and functional connectivity (FC) within the brain's default-mode network (DMN) in acute stroke patients with cognitive outcome three months post-stroke. METHODS: Patients aged between 18 and 85 years with an acute symptomatic MRI-proven unilateral ischemic middle cerebral artery infarction, who had received reperfusion therapy, were invited to participate in this longitudinal study. All patients underwent brain MRI within 24-72 h after symptom onset, and participated in a neuropsychological assessment three months post-stroke. We performed hierarchical regression analyses to explore the incremental value of baseline white matter integrity and FC beyond demographic, clinical, and macrostructural information for cognitive outcome. RESULTS: The study cohort comprised 34 patients (mean age: 64 ± 12 years, 35% female). The initial median National Institutes of Health Stroke Scale (NIHSS) score was 10, and significantly improved three months post-stroke to a median NIHSS = 1 (p < .001). Nonetheless, 50% of patients showed cognitive impairment three months post-stroke. FC of the non-lesioned anterior cingulate cortex of the affected hemisphere explained 15% of incremental variance for processing speed (p = .007), and fractional anisotropy of the non-lesioned cingulum of the affected hemisphere explained 13% of incremental variance for cognitive flexibility (p = .033). CONCLUSIONS: White matter integrity and functional MRI markers of the DMN in acute stroke explain incremental variance for post-stroke cognitive outcome beyond demographic, clinical, and macrostructural information.

External Validation of a Model for Persistent Perfusion Deficit in Patients With Incomplete Reperfusion After Thrombectomy: EXTEND-PROCEED.

BACKGROUND AND OBJECTIVES: We recently developed a model (PROCEED) that predicts the occurrence of persistent perfusion deficit (PPD) at 24 hours in patients with incomplete angiographic reperfusion after thrombectomy. This study aims to externally validate the PROCEED model using prospectively acquired multicenter data. METHODS: Individual patient data for external validation were obtained from the Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection, Tenecteplase versus Alteplase Before Endovascular Therapy for Ischemic Stroke part 1 and 2 trials, and a prospective cohort of the Medical University of Graz. The model's primary outcome was the occurrence of PPD, defined as a focal, wedge-shaped perfusion delay on 24-hour follow-up perfusion imaging that corresponds to the capillary phase deficit on last angiographic series in patients with

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

The "central vein sign": is there a place for susceptibility weighted imaging in possible multiple sclerosis?

OBJECTIVES: Susceptibility weighted imaging (SWI) may have the potential to depict the perivenous extent of white matter lesions (WMLs) in multiple sclerosis (MS). We aimed to assess the discriminatory value of the "central vein sign" (CVS). METHODS: In a 3-T magnetic resonance imaging (MRI) study, 28 WMLs in 14 patients with at least one circumscribed lesion >5 mm and not more than eight non-confluent lesions >3 mm were prospectively included. Only WMLs in FLAIR images with a maximum diameter of >5 mm were correlated to their SWI equivalent for CVS evaluation. RESULTS: Five patients fulfilled the revised McDonald criteria for MS and nine patients were given alternative diagnoses. Nineteen MS-WMLs and nine non-MS-WMLs >5 mm were detected. Consensus reading found a central vein in 16 out of 19 MS-WMLs (84 %) and in one out of nine non-MS-WMLs (11 %), respectively. The CVS proved to be a highly significant discriminator (P < 0.001) between MS-WMLs and non-MS-WMLs with a sensitivity, specificity, positive and negative predictive value and accuracy of 84 %, 89 %, 94 %, 73 % and 86 %, respectively. Inter-rater agreement was good (κ = 0.77). CONCLUSIONS: Even though the CVS is not exclusively found in MS-WMLs, SWI may be a useful adjunct in patients with possible MS. KEY POINTS: • MRI continues to yield further information concerning MS lesions. • SWI adds diagnostic information in patients with possible MS. • The "central vein sign" was predominantly seen in MS lesions. • The "central vein sign" helps discriminate between MS and non-MS lesions.

Age dependency of successful recanalization in anterior circulation stroke: the ENDOSTROKE study.

BACKGROUND: Clinical outcome after endovascular stroke therapy (EVT) for proximal anterior circulation stroke is often disappointing despite high recanalization rates. The ENDOSTROKE study aims to determine predictors of clinical outcome in patients undergoing EVT. Here we focus on the impact of age and recanalization on proximal middle cerebral artery (M1-MCA) or carotid T occlusion. METHODS: ENDOSTROKE is an investigator-initiated, industrially independent multicenter registry launched in January, 2011, for consecutive patients undergoing EVT for large-vessel stroke. This analysis focuses on patients treated in 11 academic and nonacademic stroke centers with angiographically proven M1-MCA (n = 259) or carotid T occlusion (n = 103). Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) score 2 or 3, and in patients with available Thrombolysis in Cerebral Ischemia (TICI) data (n = 309) as TICI scores 2b-3. Good outcome was defined as modified Rankin Scale (mRS) score of 0-2 assessed after 3 months or later. RESULTS: The median age was 68 years (25th and 75th percentiles: 56, 76 years), and the median National Institutes of Health Stroke Scale (NIHSS) score at admission was 16 (13, 19); 41% of the patients had a favorable (mRS scores 0-2), and 59% had an unfavorable (mRS scores 3-6) outcome; 83% reached TIMI 2-3 flow. Independent predictors of good outcome were younger age, lower initial NIHSS scores, TIMI 2/3 recanalization and lower serum glucose levels. Outcome was highly dependent on patients' age: 60% of the patients within the lowest age quartile (range: 18-56 years) experienced good clinical outcome, decreasing stepwise over 47% (57-68 years) and 37% (69-76 years) to 17% in the highest age quartile (77-94 years). The proportion of patients with poor clinical outcome despite TIMI 2/3 recanalization ('futile recanalization') increased dramatically from only 29% in the lowest age quartile over 34% and 40% (2nd and 3rd age quartiles) up to 53% in the highest age quartile. Results were similar in patients with available TICI scores, with 'futile recanalization' rates increasing from 24% to 46% (lowest to highest age quartile). CONCLUSIONS: This study emphasizes the dramatic impact of patients' age on outcome in EVT for M1-MCA or carotid T occlusion, even in the presence of recanalization. Reasons for this age-related decrease in clinically successful recanalization rates urgently need clarification and may comprise patient-related factors (age-related increase in cardioembolic strokes, collateral status, comorbidities) as well as periprocedural issues (tortuous vessel anatomy in the elderly, age-dependent negative impact of general anesthesia in EVT).

Periprocedural aspects in mechanical recanalization for acute stroke: data from the ENDOSTROKE registry.

INTRODUCTION: The ENDOSTROKE registry aims to accompany the spreading use of endovascular stroke treatment (EVT) in academic and non-academic hospitals. This analysis focuses on preprocedural imaging, patient handling and referral, as well as on different treatment modalities in mechanical recanalization. METHODS: Data for this study were from observational registry study in 12 stroke centers in Germany and Austria with online assessment of prespecified variables concerning endovascular stroke therapy. RESULTS: Data from 734 patients undergoing EVT were analyzed. Preferred imaging modality prior to EVT was CT (83 %) and CTA (78 %). In 95 %, EVT was performed under general anesthesia. In 55 % of patients, a combination of intravenous (IV) thrombolysis and EVT was used, followed by pure EVT (25 %), intra-arterial (IA) thrombolysis plus EVT (13 %) and IV + IA thrombolysis plus EVT (7 %). Intrahospital time delay until start of EVT was 91 and 99 min in anterior and vertebrobasilar circulation stroke, respectively. Average duration of EVT was 60 min. Overall thrombolysis in myocardial infarction grade 2/3 recanalization rate was 85 %. Stent retrievers were used in 75 %, being associated with higher recanalization rates than non-stent retrievers. Hemorrhagic complications (symptomatic and asymptomatic) occurred in 12 %. Overall vessel occlusion time was approximately 60 min longer in patients being referred from a primary care hospital for EVT. CONCLUSION: This study gives an overview of procedure-related factors in current EVT practice. It gives estimates on preprocedural imaging modalities, periprocedural handling, and treatment combinations used for EVT. Patient referral for EVT from primary care hospitals is associated with longer vessel occlusion times.