Multicenter validation of synthetic FLAIR as a substitute for FLAIR sequence in acute ischemic stroke.

PURPOSE: To evaluate performance of synthetic and real FLAIR for identifying early stroke in a multicenter cohort. METHODS: This retrospective study was conducted using DWI and FLAIR extracted from the Endovascular Treatment in Ischemic Stroke image registry (2017-2021). The database was partitioned into subsets according to MRI field strength and manufacturer, and randomly divided into training set (70%) used for model fine-tuning, validation set (15%), and test set (15%). In test set, five readers, blinded to FLAIR sequence type, assessed DWI-FLAIR mismatch using real and synthetic FLAIR. Interobserver agreement for DWI-FLAIR rating and concordance between synthetic and real FLAIR were evaluated with kappa statistics. Sensitivity and specificity for identification of ⩽4.5 h AIS were compared in patients with known onset-to-MRI delay using McNemar's test. RESULTS: 1454 complete MRI sets (1172 patients, median (IQR) age: 73 years (62-82); 762 women) acquired on 125 MRI units were analyzed. In test set (207 MRI), interobserver reproducibility for DWI-FLAIR mismatch labeling was substantial for real and synthetic FLAIR (Fleiss κ = 0.79 (95%CI: 0.73-0.84) and 0.77 (95%CI: 0.71-0.82), respectively). After consensus, concordance between real and synthetic FLAIR was excellent (κ = 0.85 (95%CI: 0.78-0.92)). In 141 MRI sets with known onset-to-MRI delay, diagnostic performances for ⩽4.5 h AIS identification did not differ between real and synthetic FLAIR (sensitivity: 60/71 (85%) vs 59/71 (83%), p = .56; specificity: 65/70 (93%) vs 65/70 (93%), p > 0.99). CONCLUSION: A deep-learning-based FLAIR fine-tuned on multicenter data can provide comparable performances to real FLAIR for early AIS identification. This approach may help reducing MR protocol duration and motion artifacts.

Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS. METHODS: We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH. RESULTS: 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH. CONCLUSION: CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation. REGISTRATION: Registration-URL: http://www. CLINICALTRIALS: gov ; Unique identifier: NCT01062698.

Meningioma in patients exposed to progestin drugs: results from a real-life screening program.

PURPOSE: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate). METHODS: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening. RESULTS: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up. CONCLUSION: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.

TAGE Score for Symptomatic Intracranial Hemorrhage Prediction After Successful Endovascular Treatment in Acute Ischemic Stroke.

BACKGROUND: Determine if early venous filling (EVF) after complete successful recanalization with mechanical thrombectomy in acute ischemic stroke is an independent predictor of symptomatic intracranial hemorrhage (sICH) and integrate EVF into a risk score for sICH prediction. METHODS: Consecutive patients with anterior acute ischemic stroke treated by mechanical thrombectomy issued from patients enrolled in the THRACE trial (Thrombectomie des Artères Cérébrales) and from 2 prospective registries were included and divided into a derivation (Center I; n=402) and validation cohorts (THRACE and center 2; n=507). EVF was evaluated by 2 blinded readers. sICH was defined according to the modified European cooperative acute stroke study II. Clinical and radiological data were analyzed in the derivation cohort (C1) to identify independent predictors of sICH and construct a predictive score test on the validation cohort (THRACE + C2). RESULTS: Symptomatic ICH rate was similar between the two cohorts (9.9% and 8.9% respectively, P=0.9). Time from onset-to-successful recanalization >270 minutes (odds ratio [OR], 7.8 [95% CI, 2.5-24]), Alberta Stroke Program Early CT Score (≤5 [OR, 2.49 (95% CI, 1.8-8.1) or 6-7 [OR, 1.15 (95% CI, 1.03-4.46)]), glucose blood level >7 mmol/L (OR, 2.92 [95% CI, 1.26-6.7]), and EVF presence (OR, 11.9 [95% CI, 3.8-37.5]) were independent predictors of sICH and constituted the Time-Alberta Stroke Program Early CT-Glycemia-EVF score. Time-Alberta Stroke Program Early CT-Glycemia-EVF score was associated with an increased risk of sICH in the derivation cohort (OR increase per unit, 1.99 [95% CI, 1.53-2.59]; P<0.001) with area under the curve, 0.832 [95% CI, 0.767-0.898]. The score had good performance in the validation cohort (area under the curve, 0.801 [95% CI, 0.69-0.91]). CONCLUSIONS: Time-Alberta Stroke Program Early CT-Glycemia-EVF score is a simple tool with readily available clinical variables with good performances for sICH prediction after mechanical thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01062698.

Small vessel disease and collaterals in ischemic stroke patients treated with thrombectomy.

BACKGROUND AND PURPOSE: To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS). METHODS: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals' adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0-2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores. RESULTS: A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52-0.89] and aOR 0.66; 95%CI [0.5-0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20-0.79]). CONCLUSION: Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals.

Synthetic FLAIR as a Substitute for FLAIR Sequence in Acute Ischemic Stroke.

Background In acute ischemic stroke (AIS), fluid-attenuated inversion recovery (FLAIR) is used for treatment decisions when onset time is unknown. Synthetic FLAIR could be generated with deep learning from information embedded in diffusion-weighted imaging (DWI) and could replace acquired FLAIR sequence (real FLAIR) and shorten MRI duration. Purpose To compare performance of synthetic and real FLAIR for DWI-FLAIR mismatch estimation and identification of patients presenting within 4.5 hours from symptom onset. Materials and Methods In this retrospective study, all pretreatment and early follow-up (<48 hours after symptom onset) MRI data sets including DWI (b = 0-1000 sec/mm2) and FLAIR sequences obtained in consecutive patients with AIS referred for reperfusion therapies between January 2002 and May 2019 were included. On the training set (80%), a generative adversarial network was trained to produce synthetic FLAIR with DWI as input. On the test set (20%), synthetic FLAIR was computed without real FLAIR knowledge. The DWI-FLAIR mismatch was evaluated on both FLAIR data sets by four independent readers. Interobserver reproducibility and DWI-FLAIR mismatch concordance between synthetic and real FLAIR were evaluated with κ statistics. Sensitivity and specificity for identification of AIS within 4.5 hours were compared in patients with known onset time by using McNemar test. Results The study included 1416 MRI scans (861 patients; median age, 71 years [interquartile range, 57-81 years]; 375 men), yielding 1134 and 282 scans for training and test sets, respectively. Regarding DWI-FLAIR mismatch, interobserver reproducibility was substantial for real and synthetic FLAIR (κ = 0.80 [95% CI: 0.74, 0.87] and 0.80 [95% CI: 0.74, 0.87], respectively). After consensus, concordance between real and synthetic FLAIR was almost perfect (κ = 0.88; 95% CI: 0.82, 0.93). Diagnostic value for identifying AIS within 4.5 hours did not differ between real and synthetic FLAIR (sensitivity: 107 of 131 [82%] vs 111 of 131 [85%], P = .2; specificity: 96 of 104 [92%] vs 96 of 104 [92%], respectively, P > .99). Conclusion Synthetic fluid-attenuated inversion recovery (FLAIR) had diagnostic performances similar to real FLAIR in depicting diffusion-weighted imaging-FLAIR mismatch and in helping to identify early acute ischemic stroke, and it may accelerate MRI protocols. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Carroll and Hurley in this issue.

Perfusion Imaging and Clinical Outcome in Acute Ischemic Stroke with Large Core.

OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue ("core"). Perfusion imaging may identify a subset of patients with large core who benefit from MT. METHODS: We compared two cohorts of LVO-related patients with large core (>50 ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6 hours from onset by either MT + Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale ≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio = critical hypoperfusion/core volume). RESULTS: Overall, 107 patients were included (56 MT + BMM and 51 BMM): Mean age was 68 ± 15 years, median core volume 99 ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the two groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (pinteraction < 0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95% CI] = 6.8 [1.7-27.0] vs 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio ≥1.8 in the subgroup with core ≥70 ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT + BMM group regardless of the MMRatio. INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. ANN NEUROL 2021;90:417-427.

Impact of Repeated Clot Retrieval Attempts on Infarct Growth and Outcome After Ischemic Stroke.

OBJECTIVE: To determine whether the association between increasing number of clot retrieval attempts (CRA) and unfavorable outcome is due to an increase in emboli to new territory (ENT) and greater infarct growth (IG) in successfully recanalized patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). METHODS: Data were extracted from 2 pooled multicentric prospective registries of consecutive patients with anterior AIS-LVO treated with mechanical thrombectomy (MT) between January 2016 and 2019. Patients with pretreatment and 24-hour posttreatment diffusion-weighted imaging (DWI) achieving successful recanalization, defined as expanded Thrombolysis in Cerebral Infarction Scale score of 2B, 2C, or 3, were included. ENT were assessed and IG was measured by voxel-based segmentation after DWI coregistration. Associations between number of CRA, ENT, IG, and 3-month outcome were analyzed. RESULTS: Four hundred nineteen patients achieving successful recanalization were included. ENT occurrence was strongly correlated with increasing CRA (ρ = 0.73, p = 10-4). In multivariable linear analysis, IG was independently associated with CRA (ß = 1.6 per retrieval attempt, 95% confidence interval [CI] 0.97-9.74, p = 0.03) and ENT (ß = 2.7 [95% CI 1.21-4.1], p = 0.03). Unfavorable functional outcome (3-month modified Rankin Scale score >2) increased with each additional CRA. IG was an independent predictor of unfavorable outcome (odds ratio 1.05 [95% CI 1.02-1.07] per 1-mL IG increase, p = 10-4) in binary logistic regression analysis. CONCLUSIONS: Increasing number of CRA in acute stroke is correlated with an increased ENT rate and increased IG volume, affecting functional outcome even when successful recanalization is achieved. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, for patients with acute stroke undergoing successful recanalization, an increasing number of CRA is associated with poorer functional outcome.

Tissue outcome prediction in hyperacute ischemic stroke: Comparison of machine learning models.

Machine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI0), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI24h) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI0 as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median [IQR] Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 [0.29-0.68]) than U-Net (0.48 [0.18-0.68]), Random Forests (0.51 [0.27-0.66]), and clinical thresholding method (0.45 [0.25-0.62]) (P < 0.001). In this benchmark of ML models for tissue outcome prediction in AIS, Gradient Boosting outperformed other ML models and clinical thresholding method and is thus promising for future decision-making.

An evaluation of the differences in paediatric skeletal trauma between fatal simple short falls and physical abuse blunt impact loads: An international multicentre pilot study.

In cases where a deceased child exhibits trauma as a result of a physical abuse blunt impact load, a parent/caregiver may provide a simple short fall (SSF) as the justification for that trauma. The skeletal fractures remain difficult to differentiate between a SSF and physical abuse however, as both are the result of a blunt impact load, and are therefore biomechanically alike, and the rare nature of these fatalities means only anecdotal research has been available to validate such claims. The aim of this pilot study was to investigate if there may be differences in the skeletal fracture patterns and types resulting from SSFs compared with those resulting from physical abuse blunt impacts. Paediatric (<10 years) cases of fatal SSFs (≤1.5 m) and physical abuse were collected from the Victorian Institute of Forensic Medicine (Australia), Institut Médico-Légal de Paris (France), University of Pretoria (South Africa) and Great Ormond Street Hospital (England). For each case the intrinsic and extrinsic variables were recorded from medico-legal reports and skeletal trauma was documented using post-mortem computed tomography scans and/or skeletal surveys. Three SSFs and 18 physical abuse cases were identified. Of the SSF cases, two exhibited fractures; both of which were simple linear neurocranial fractures. Comparatively, 12 of the physical abuse cases exhibited fractures and these were distributed across the skeleton; 58% located only in the skull, 17% only in the post-cranial and 25% located in both. Skull fracture types were single linear, multiple linear and comminuted. This pilot study suggests, anecdotally, there may be differences in the fracture patterns and types between blunt impact loads resulting from a SSF and physical abuse. This data will form the foundation of the Registry of Paediatric Fatal Fractures (RPFF) which, with further multicentre contributions, would allow this finding to be validated.

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Accelerated MR Evaluation of Patients with Suspected Large Arterial Vessel Occlusion: Diagnostic Performances of the FLAIR Vessel Hyperintensities.

BACKGROUND: Fluid attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) document slowed vascular flow at the level and after the occlusion site patients with acute ischemic stroke (AIS). We aimed to assess the accuracy of FVH for the confirmation and location of a large vessel occlusion (LVO). METHODS: Three radiologists reviewed the FLAIR sequence of the admission MRI exam of patients with suspected AIS at a single academic center. Readers were provided with the main clinical deficit with National Institute of Health Stroke Severity score and were asked to identify and locate an LVO when appropriate. Kappa coefficients were calculated for agreement along with diagnosis performances of FVH to recognize and locate an LVO with digital subtracted angiography (DSA) as gold standard. RESULTS: Among 125 patients screened with MRI for a suspected AIS, 96 (81%) were diagnosed with AIS and 47 (38%) patients had an anterior LVO of whom 25 (20%) had a DSA for mechanical thrombectomy. Kappa coefficients for intra- and inter-readers were good to excellent. Overall, the sensitivity and the specificity of the FVH to predict an anterior LVO was 0.98 (95% confidence interval [CI]: 0.94-1) and 0.86 (95% CI: 0.79-0.96), respectively, while PPV and NPV were 0.87 (95% CI: 0.85-0.95) and 0.98 (0.97-1), respectively. FVH also showed good to excellent accuracy for identifying M1 and M2 versus internal carotid artery occlusion site. CONCLUSION: We found that FVH demonstrated excellent diagnostic performances for the identification of LVO and its level with good to excellent reproducibility. This MRI radio marker of occlusion provides additional arguments and may speed-up the detection of potential candidates for MT.

Increased Wall Enhancement During Follow-Up as a Predictor of Subsequent Aneurysmal Growth.

Background and Purpose- Absence of arterial wall enhancement (AWE) of unruptured intracranial aneurysms (UIA) has shown promise at predicting which aneurysms will not rupture. We here tested the hypothesis that increased enhancement during follow-up (increased intensity, extension, or thickness or appearance of de novo enhancement), assessed using vessel wall magnetic resonance imaging, was associated with higher rates of subsequent growth. Methods- Patients with UIA were included between 2012 and 2018. Two readers independently rated AWE modification on 3T vessel wall magnetic resonance imaging, and morphological changes on time-of-flight magnetic resonance angiography during follow-up. Results- A total of 129 patients harboring 145 UIA (mean size 4.1 mm) met study criteria, of which 12 (8.3%) displayed morphological growth at 2 years. Of them, 8 demonstrated increased AWE during follow-up before or concurrently to morphological growth, and 4 had preexisting AWE that remained stable before growth. In the remaining 133 (nongrowing) UIAs, no AWE modifications were found. In multivariable analysis, increased AWE, not size, was associated with UIA growth (relative risk, 26.1 [95% CI, 7.4-91.7], P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for UIA growth of increased AWE during follow-up were, respectively, of 67%, 100%, 96%, and 100%. Conclusions- Increased AWE during follow-up of conservatively managed UIAs predicts aneurysm growth over a 2-year period. This may impact UIA management towards closer monitoring or preventive treatment. Replication in a different setting is warranted.

Relationships between brain perfusion and early recanalization after intravenous thrombolysis for acute stroke with large vessel occlusion.

In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR (P = 0.006), shorter thrombus on T2*-imaging (P < 0.001) and more distal occlusion (P = 0.006). However, the relationship between HIR and early recanalization was robust only for thrombus length <14 mm. In summary, the present study disclosed an association between lower HIR and early post-thrombolysis recanalization. Early post-thrombolysis recanalization is therefore determined not only by thrombus site and length but also by severity of ischemia.

MT-DRAGON score for outcome prediction in acute ischemic stroke treated by mechanical thrombectomy within 8 hours.

OBJECTIVES: The MRI-DRAGON score includes clinical and MRI parameters and demonstrates a high specificity in predicting 3 month outcome in patients with acute ischemic stroke (AIS) treated with intravenous tissue plasminogen activator (IV tPA). The aim of this study was to adapt this score to mechanical thrombectomy (MT) in a large multicenter cohort. METHODS: Consecutive cases of AIS treated by MT between January 2015 and December 2017 from three stroke centers were reviewed (n=1077). We derived the MT-DRAGON score by keeping all variables of the MRI-DRAGON score (age, initial National Institutes of Health Stroke Scale score, glucose level, pre-stroke modified Rankin Scale (mRS) score, diffusion weighted imaging-Alberta Stroke Program Early CT score ≤5) and considering the following variables: time to groin puncture instead of onset to IV tPA time and occlusion site. Unfavorable 3 month outcome was defined as a mRS score >2. Score performance was evaluated by c statistics and an external validation was performed. RESULTS: Among 679 included patients (derivation and validation cohorts, n=431 and 248, respectively), an unfavorable outcome was similar between the derivation (51.5%) and validation (58.1%, P=0.7) cohorts, and was significantly associated with all MT-DRAGON parameters in the multivariable analysis. The c statistics for unfavorable outcome prediction was 0.83 (95%CI 0.79 to 0.88) in the derivation and 0.8 (95%CI 0.75 to 0.86) in the validation cohort. All patients (n=55) with an MT-DRAGONscore ≥11 had an unfavorable outcome and 60/63 (95%) patients with an MT-DRAGON score ≤2 points had a favorable outcome. CONCLUSION: The MT-DRAGON score is a simple tool, combining admission clinical and radiological parameters that can reliably predict 3 month outcome after MT.

White matter hyperintensity burden in patients with ischemic stroke treated with thrombectomy.

INTRODUCTION: To determine the influence of white matter hyperintensity (WMH) burden on functional outcome, rate of symptomatic intracerebral hemorrhage (sICH), and procedural success in patients with acute ischemic stroke (AIS) treated by mechanical thrombectomy (MT) with current stentriever/aspiration devices. METHODS: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. WMH volumes were obtained by semiautomated planimetric segmentation and tested in association with the rate of favorable outcome (90-day functional independence), substantial recanalization after MT, and sICH. RESULTS: A total of 496 participants were included between 2015 and 2018 (50% female, mean age 68.1 ± 15.0 years). Overall, 434 (88%) patients presented with detectable WMH (mean ± SD 4.93 ± 7.7). Patients demonstrated increasingly worse outcomes with increasing WMH volumes (odds ratio [aOR]1.05 per 1-cm3 increase for unfavorable outcome, 95% confidence interval [CI] 1.01-1.06, p = 0.014). Fifty-seven percent of patients in the first quartile of WMH volume vs 28% in the fourth quartile demonstrated favorable outcome (p < 0.001). WMH severity was not associated with sICH rate (aOR 0.99, 95% CI 0.93-1.04, p = 0.66), nor did it influence recanalization success (aOR 0.99, 95% CI 0.96-1.02, p = 0.84). CONCLUSION: Our study provides evidence that in patients with AIS due to LVO and high burden of WMH as assessed by pretreatment MRI, the safety and efficacy profiles of MT are similar to those in patients with lower WMH burden and confirms that they are at higher risk of unfavorable outcome. Because more than a quarter of patients in the highest WMH quartile experienced favorable 3 months outcome, WMH burden may not be a good argument to deny MT. CLINICALTRIALSGOV IDENTIFIER: NCT01062698.

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Benefit from revascularization after thrombectomy according to FLAIR vascular hyperintensities-DWI mismatch.

OBJECTIVES: We tested whether FLAIR vascular hyperintensities (FVH)-DWI mismatch could identify candidates for thrombectomy most likely to benefit from revascularization. METHODS: We retrospectively reviewed 100 patients with proximal MCA occlusion from 18 stroke centers randomized in the IV-thrombolysis plus mechanical thrombectomy arm of the THRACE trial (2010-2015). We tested the associations between successful revascularization on digital subtraction angiography (modified Thrombolysis in Cerebral Infarction 2b/3) and 3-month favorable outcome (modified Rankin Scale score ≤ 2), stratified on FVH-DWI mismatch status, with secondary analyses adjusted on National Institutes of Health Stroke Scale (NIHSS) and DWI lesion volume. RESULTS: FVH-DWI mismatch was present in 79% of patients, with a similar prevalence at 1.5 T (80%) and 3 T (78%). Successful revascularization (74%) was more frequent in patients with FVH-DWI mismatch (63/79, 80%) than in patients without (11/21, 52%), p = 0.01. The OR of favorable outcome for revascularization were 15.05 (95% CI 3.12-72.61, p < 0.001) in patients with FVH-DWI mismatch and 0.83 (95% CI 0.15-4.64, p = 0.84) in patients without FVH-DWI mismatch (p = 0.011 for interaction). Similar results were observed after adjustment for NIHSS (OR = 12.73 [95% CI 2.69-60.41, p = 0.001] and 0.96 [95% CI 0.15-6.30, p = 0.96]) or for DWI volume (OR = 12.37 [95% CI 2.76-55.44, p = 0.001] and 0.91 [95% CI 0.16-5.33, p = 0.92]) in patients with and without FVH-DWI mismatch, respectively. CONCLUSIONS: The FVH-DWI mismatch identifies patients likeliest to benefit from revascularization, irrespective of initial DWI lesion volume and clinical stroke severity, and could serve as a useful surrogate marker for penumbral evaluation. KEY POINTS: • The FVH-DWI mismatch, defined by FLAIR vascular hyperintensities (FVH) located beyond the boundaries of the DWI lesion, is associated with large penumbra. • Among stroke patients with proximal middle cerebral artery occlusion referred for thrombectomy, those with FVH-DWI mismatch are most likely to benefit from revascularization. • FVH-DWI mismatch provides an alternative to PWI-DWI mismatch in order to select patients who are candidates for thrombectomy.