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Background: Timely revascularization in acute arterial ischemic stroke (AIS) is paramount for optimal outcomes. However, factors causing treatment delays in pediatric AIS remain understudied. We investigated determinants affecting the time from symptom onset or last-known-well to the start of recanalization treatment in pediatric AIS., Methods: We conducted an ancillary analysis of the French KID-CLOT study (The National Retrospective Study of Recanalization Treatments in Pediatric Arterial Ischemic Stroke), considering patients with pediatric AIS receiving recanalization treatments (IV thrombolysis IVT and mechanical thrombectomy) from 2015 to 2018. The study assessed prehospital triage's impact, direct versus transferred admissions, and unit type (pediatric versus adult) on treatment delay and clinical outcomes using modified Rankin Scale at 1 year., Results: Among 68 patients (median age, 11 [IQR, 4-16]; initial PedNIHSS, 13 [IQR, 7-19]), treatment modalities were IVT (n=31), and mechanical thrombectomy (n=23), and IVT+mechanical thrombectomy (n=14). Prehospital triage significantly reduced last-known-well to treatment delay (overall, 229 versus 270 minutes; P =0.01), most notably for and mechanical thrombectomy ( P <0.001). There was no substantial delay difference between direct and transferred admissions, or between unit types, although a trend favored adult units (370.3 versus 436.73 minutes; P =0.06). Prehospital triage correlated with improved outcomes, with a shift to lower modified Rankin Scale scores ( P =0.021)., Conclusions: For pediatric AIS treated with reperfusion therapy, prehospital triage emerges as a pivotal factor in reducing treatment delays and enhancing outcomes. These findings underscore the need for a dedicated prehospital stroke protocol for children., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03887143., Competing Interests: None.

Background: Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients <80 versus ≥80 years old, (1) the effect of successful recanalization on DWIR and (2) the impact of DWIR on functional outcome., Methods: We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected., Results: Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6-35) in patients ≥80, and 19% (interquartile range, 10-34) in patients <80 ( P =0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 ( P =0.004) and <80 ( P =0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% ( P >0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 ( P =0.003) and <80 ( P =0.013) patients; the effect of DWIR% on outcome was not influenced by the age group ( P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion., Competing Interests: Disclosures Dr Benzakoun reports travel support from Guerbet LLC. Dr Bricout reports compensation from Stryker for consultant services and compensation from Qapel Medical for consultant services. Dr Turc reports compensation from Guerbet France for other services. The other authors report no conflicts.

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.

Background and Purpose: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage., Methods: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography., Results: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography., Conclusions: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.

Background and Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset., Methods: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT-) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences., Results: A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT- group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88-1.34]; P =0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7-1.2]; P =0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63-1.37]; P =0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0-2; aOR, 0.98 [95% CI, 0.77-1.25]; P =0.89), and mortality (aOR, 0.95 [95% CI, 0.72-1.26]; P =0.76) at 90 days did not differ between the groups., Conclusions: Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.

Background and Purpose: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice., Methods: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. The present study is a retrospective analysis of 4029 stroke patients with anterior large vessel occlusions treated with thrombectomy between January 2015 and May 2020 in 18 centers. We systematically collected procedural data, incidence of embolic complications, perforations and dissections, clinical outcome at 90 days, and hemorrhagic complications., Results: Procedural complications occurred in 7.99% (95% CI, 7.17%-8.87%), and embolus to a new territory (ENT) was the most frequent (5.2%). Predictors of ENTs were terminal carotid/tandem occlusion (odds ratio [OR], 5 [95% CI, 2.03-12.31]; P <0.001) and an increased total number of passes (OR, 1.22 [95% CI, 1.05-1.41]; P =0.006). ENTs were associated to worse clinical outcomes (90-day modified Rankin Scale score, 0-2; adjusted OR, 0.4 [95% CI, 0.25-0.63]; P <0.001), increased mortality (adjusted OR, 1.74 [95% CI, 1.2-2.53]; P <0.001), and symptomatic intracerebral hemorrhage (adjusted OR, 1.87 [95% CI, 1.15-3.03]; P =0.011). Perforations occurred in 1.69% (95% CI, 1.31%-2.13%). Predictors of perforations were terminal carotid/tandem occlusions (39.7% versus 27.6%; P =0.028). 40.7% of patients died at 90 days, and the overall rate of poor outcome was 74.6% in case of perforation. Dissections occurred in 1.46% (95% CI, 1.11%-1.88%) and were more common in younger patients (median age, 64.2 versus 70.2 years; P =0.002). Dissections did not affect the clinical outcome at 90 days. Besides dissection, complications were independent of the thrombectomy technique., Conclusions: Thrombectomy complication rate is not negligible, and ENTs were the most frequent. ENTs and perforations were associated with disability and mortality, and terminal carotid/tandem occlusions were a risk factor. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.

Objective: Individualized patient selection for mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) and large ischemic core (LIC) at baseline is an unmet need. We tested the hypothesis that assessing the functional relevance of both infarcted and hypoperfused brain tissue would improve the selection framework of patients with LIC for MT., Methods: We performed a multicenter, retrospective study of adults with LIC (ischemic core volume >70 mL on MRI diffusion-weighted imaging) with MRI perfusion treated with MT or best medical management (BMM). Primary outcome was 3-month modified Rankin Scale (mRS), favorable if 0-3. Global and regional eloquence-based core perfusion mismatch ratios were derived. The predictive accuracy for clinical outcome of eloquent regions involvement was compared in multivariable and bootstrap random forest models., Results: A total of 138 patients with baseline LIC were included (MT n = 96 or BMM n = 42; mean age ± SD, 72.4 ± 14.4 years; 34.1% female; mRS 0-3: 45.1%). Mean core and critically hypoperfused volume were 100.4 mL ± 36.3 mL and 157.6 ± 56.2 mL, respectively, and did not differ between groups. Models considering the functional relevance of the infarct location showed a better accuracy for the prediction of mRS 0-3 with a c statistic of 0.76 and 0.83 for logistic regression model and bootstrap random forest testing sets, respectively. In these models, the interaction between treatment effect of MT and the mismatch was significant ( p = 0.04). In comparison, in the logistic regression model disregarding functional eloquence, the c statistic was 0.67 and the interaction between MT and the mismatch was insignificant., Conclusions: Considering functional eloquence of hypoperfused tissue in patients with a large infarct core at baseline allows for a more precise estimation of treatment expected benefit., Classification of Evidence: This study provides Class II evidence that, in patients with AIS and LIC, considering the functional eloquence of the infarct location improves prediction of disability status at 3 months., (© 2021 American Academy of Neurology.)

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 (β = 1.6 per retrieval attempt, 95% confidence interval [CI] 0.97-9.74, p = 0.03) and ENT (β = 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., (© 2021 American Academy of Neurology.)

Background and Purpose: We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics., Methods: Individual MT procedural data from 5 centers of the Endovascular Treatment in Ischemic Stroke registry and 2 additional high-volume stroke centers were pooled. Operator experience was defined for each operator as a continuous variable, cumulating the number of MT procedures performed since January 2015, as MT became standard of care or, if later than this date, since the operator started performing mechanical thrombectomies in autonomy. We tested the associations between operator's experience and procedural metrics., Results: A total of 4516 procedures were included, performed by 36 operators at 7 distinct centers, with a median of 97.5 endovascular treatment procedures per operator (interquartile range, 57-170.2) over the study period. Higher operator's experience, analyzed as a continuous variable, was associated with a significantly shorter procedural duration (β estimate, -3.98 [95% CI, -5.1 to -2.8]; P <0.001), along with local anesthesia and M1 occlusion location in multivariable models. Increasing experience was associated with better Thrombolysis in Cerebral Infarction scores (estimate, 1.02 [1-1.04]; P =0.013)., Conclusions: In trained interventional neuroradiologists, increasing experience in MT is associated with significantly shorter procedural duration and better reperfusion rates, with a theoretical ceiling effect observed after around 100 procedures. These results may inform future training and practice guidelines to set minimal experience standards before autonomization, and to set-up operators' recertification processes tailored to individual case volume and prior experience.

Background and Purpose: Significant hemorrhage expansion (sHE) is a known predictor of poor outcome after an intracerebral hemorrhage (ICH) in adults but remains poorly reported in children. In a large inception cohort, we aimed to explore the prevalence of sHE, its associations with clinical outcomes, and its clinical-imaging predictors in children., Methods: Children admitted between January 2000 and March 2020 at a quaternary care pediatric hospital were screened for inclusion. Sample was restricted to children with 2 computed tomography scans within 72 hours of ICH onset, and a minimal clinical follow-up of months. sHE was defined as an increase from baseline ICH volume by 6 cc or 33% on follow-up computed tomography. Clinical outcome was assessed at 12 months with the King's Outcome Scale for Childhood Head Injury score and defined as favorable for scores ≥5., Results: Fifty-two children met inclusion criteria, among which 8 (15%) demonstrated sHE, and 18 (34.6%) any degree of expansion. Children with sHE had more frequent coagulation disorders (25.0% versus 2.3%; P =0.022). After multivariable adjustment, only the presence of coagulation disorders at baseline remained independently associated with sHE (adjusted odds ratio, 14.4 [95% CI, 1.04-217]; P =0.048). sHE was independently associated with poor outcome (King's Outcome Scale for Childhood Head Injury <5A, odds ratio, 5.77 [95% CI, 1.01-38.95]; P =0.043)., Conclusions: sHE is a frequent phenomenon after admission for a pediatric ICH and more so in children with coagulation defects. As sHE was strongly associated with poorer clinical outcomes, these data mandate a baseline coagulation work up and questions the need for protocolized repeat head computed tomography in children admitted for pediatric ICH.

No controlled pharmacological studies are available in the field of pediatric stroke, except for sickle cell disease. Therefore, while pharmacological and mechanical recanalization treatments have repeatedly shown clinical benefit in adults with arterial ischemic stroke, pediatric strokologists still cannot base their therapeutic management (including hyperacute strategies) on high-level evidence. Once again, pediatricians face the same dichotomic choice: adapting adult procedures now versus waiting-for a long time-for the corresponding pediatric trials. One way out is building a compromise based on observational studies with large, longitudinal, comprehensive, real-life, and multisource dataset. Two recent high-quality observational studies have delivered promising conclusions on recanalization treatments in pediatric arterial ischemic stroke. TIPSTER (Thrombolysis in Pediatric Stroke Extended Results) showed that the risk of severe intracranial hemorrhage after intravenous thrombolysis is low; the Save Childs Study reported encouraging data about pediatric thrombectomy. Beyond the conclusion of a satisfactory global safety profile, a thorough analysis of the methods, populations, results, and therapeutic complications of these studies helps us to refine indications/contraindications and highlights the safeguards we need to rely on when discussing thrombolysis and thrombectomy in children. In conclusion, pediatric strokologists should not refrain from using clot lysis/retrieval tools in selected children with arterial ischemic stroke. But the implementation of hyperacute care is only feasible if the right candidate is identified through the sharing of common adult/pediatric protocols and ward collaboration, formalized well before the child's arrival. These anticipated protocols should never undervalue contraindications from adult guidelines and must involve the necessary pediatric expertise when facing specific causes of stroke, such as focal cerebral arteriopathy of childhood.

During the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organization recommended measures to mitigate the outbreak such as social distancing and confinement. Since these measures have been put in place, anecdotal reports describe a decrease in the number of endovascular therapy (EVT) treatments for acute ischemic stroke due to large vessel occlusion. The purpose of our study was to determine the effect on EVT for patients with acute ischemic stroke during the COVID-19 confinement. In this retrospective, observational study, data were collected from November 1, 2019, to April 15, 2020, at 17 stroke centers in countries where confinement measures have been in place since March 2020 for the COVID-19 pandemic (Switzerland, Italy, France, Spain, Portugal, Germany, Canada, and United States). This study included 1600 patients treated by EVT for acute ischemic stroke. Date of EVT and symptom onset-to-groin puncture time were collected. Mean number of EVTs performed per hospital per 2-week interval and mean stroke onset-to-groin puncture time were calculated before confinement measures and after confinement measures. Distributions (non-normal) between the 2 groups (before COVID-19 confinement versus after COVID-19 confinement) were compared using 2-sample Wilcoxon rank-sum test. The results show a significant decrease in mean number of EVTs performed per hospital per 2-week interval between before COVID-19 confinement (9.0 [95% CI, 7.8-10.1]) and after COVID-19 confinement (6.1 [95% CI, 4.5-7.7]), ( P <0.001). In addition, there is a significant increase in mean stroke onset-to-groin puncture time ( P <0.001), between before COVID-19 confinement (300.3 minutes [95% CI, 285.3-315.4]) and after COVID-19 confinement (354.5 minutes [95% CI, 316.2-392.7]). Our preliminary analysis indicates a 32% reduction in EVT procedures and an estimated 54-minute increase in symptom onset-to-groin puncture time after confinement measures for COVID-19 pandemic were put into place.

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.

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-cm 3 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., (© 2019 American Academy of Neurology.)

Background and Purpose- In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus. In this proof-of-concept study, we tested the hypothesis that good collaterals independently predict post-IVT recanalization before thrombectomy. Methods- Patients from the registries of 6 French stroke centers with the following criteria were included: (1) acute stroke with large vessel occlusion treated with IVT and referred for thrombectomy between May 2015 and March 2017; (2) pre-IVT brain magnetic resonance imaging, including diffusion-weighted imaging, T2*, MR angiography, and dynamic susceptibility contrast perfusion-weighted imaging; and (3) ER evaluated ≤3 hours from IVT start on either first angiographic run or noninvasive imaging. A collateral flow map derived from perfusion-weighted imaging source data was automatically generated, replicating a previously validated method. Thrombus length was measured on T2*-based susceptibility vessel sign. Results- Of 224 eligible patients, 37 (16%) experienced ER. ER occurred in 10 of 83 (12%), 17 of 116 (15%), and 10 of 25 (40%) patients with poor/moderate, good, and excellent collaterals, respectively. In multivariable analysis, better collaterals were independently associated with ER ( P=0.029), together with shorter thrombus ( P<0.001) and more distal occlusion site ( P=0.010). Conclusions- In our sample of patients with stroke imaged with perfusion-weighted imaging before IVT and intended for thrombectomy, better collaterals were independently associated with post-IVT recanalization, supporting our hypothesis. These findings strengthen the idea that advanced imaging may play a key role for personalized medicine in identifying patients with large vessel occlusion most likely to benefit from IVT in the thrombectomy era.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Background and Purpose- The acute management of stroke patients requires a fast and efficient screening imaging modality. We compared workflow and functional outcome in acute ischemic stroke patients screened by magnetic resonance imaging (MRI) or computed tomography (CT) before treatment in the THRACE trial (Thrombectomie des Artères Cérébrales), with the emphasis on the duration of the imaging step. Methods- The THRACE randomized trial (June 2010 to February 2015) evaluated the efficacy of mechanical thrombectomy after intravenous tPA (tissue-type plasminogen activator) in ischemic stroke patients with proximal occlusion. The choice of screening imaging modality was left to each enrolling center. Differences between MRI and CT groups were assessed using univariable analysis and the impact of imaging modality on favorable 3-month functional outcome (modified Rankin Scale score of ≤2) was tested using multivariable logistic regression. Results- Four hundred one patients were included (25 centers), comprising 299 MRI-selected and 102 CT-selected patients. Median baseline National Institutes of Health Stroke Scale score was 18 in both groups. MRI scan duration (median [interquartile range]) was longer than CT (MRI: 13 minutes [10-16]; CT: 9 minutes [7-12]; P<0.001). Stroke-onset-to-imaging time (MRI: median 114 minutes [interquartile range, 89-138]; CT: 107 minutes [88-139]; P=0.19), onset-to-intravenous tPA time (MRI: 150 minutes [124-179]; CT: 150 minutes [123-180]; P=0.38) and onset-to-angiography-suite time (MRI: 200 minutes [170-250]; CT: 213 minutes [180-246]; P=0.57) did not differ between groups. Imaging modality was not significantly associated with functional outcome in the multivariable analysis. Conclusions- Although MRI scan duration is slightly longer than CT, MRI-based selection for acute ischemic stroke patients is accomplished within a timeframe similar to CT-based selection, without delaying treatment or impacting functional outcome. This should help to promote wider use of MRI, which has inherent imaging advantages over CT. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01062698.

Background and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Objectives: To further improve the distinction between primary angiitis of the CNS (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS)., Methods: We compared 2 large French cohorts of patients with PACNS (n = 110, retrospectively and prospectively enrolled) and RCVS (n = 173, prospectively enrolled)., Results: Patients with RCVS were predominantly female ( p < 0.0001), with migraines ( p < 0.0001), and were more often exposed to vasoactive substances ( p < 0.0001) or postpartum ( p = 0.002) than patients with PACNS. Headache, especially thunderclap headache, was more frequent in RCVS (both p < 0.0001). Thunderclap headache was absent in only 6% of patients with RCVS and was mainly recurrent (87%) and provoked (77%) mostly by sexual intercourse, exertion, or emotion. All other neurologic symptoms (motor deficit, seizure, cognitive disorder, or vigilance impairment, all p < 0.0001) were more frequent in PACNS. At admission, brain CT or MRI was abnormal in all patients with PACNS and in 31% of patients with RCVS ( p < 0.0001). Acute ischemic stroke was more frequent in PACNS than in RCVS ( p < 0.0001). Although intracerebral hemorrhage was more frequent in PACNS ( p = 0.006), subarachnoid hemorrhage and vasogenic edema predominated in RCVS ( p = 0.04 and p = 0.01, respectively). Multiple small deep infarcts, extensive deep white matter lesions, tumor-like lesions, or multiple gadolinium-enhanced lesions were observed only in PACNS, whereas cervical artery dissection was found only in RCVS., Conclusions: Our study confirms that careful analysis of clinical context, headache features, and patterns of brain lesions can distinguish PACNS and RCVS within the first few days of admission in most cases. However, diagnosis remains challenging in a few cases., (© 2018 American Academy of Neurology.)

Background and Purpose- We aimed to analyze the long-term outcomes of patients with primary central nervous system vasculitis according to the different therapeutic strategies used to induce remission. Methods- We assessed the rate of prolonged remission (defined by the absence of relapse at ≥12 months after diagnosis) and the functional status at last follow-up in patients with primary central nervous system vasculitis included in the French cohort, who achieved a first remission according to the 3 main groups of treatments administered: glucocorticoids only (group 1); induction treatment with glucocorticoids and an immunosuppressant, but no maintenance (group 2); and combined treatment with glucocorticoids and an immunosuppressant for induction followed by maintenance therapy (group 3). Good functional status was defined as a modified Rankin Scale score ≤2 at the last follow-up. Results- Remission was achieved with the initial induction treatment in 106 (95%) of the 112. Prolonged remission without relapse was observed in 70 (66%) patients after 57 (12-198) months of follow-up. A good functional status at last follow-up (ie, modified Rankin Scale score ≤2) was observed in 63 (56%) patients. Overall mortality was 8%. The initial severity and the radiological presentations were comparable in the 3 treatment groups. More prolonged remissions ( P=0.003) and a better functional status at the last follow-up ( P=0.0004) were observed in group 3. In multivariate analysis, the use of maintenance therapy was associated with prolonged remission (odds ratio, 4.32 [1.67-12.19]; P=0.002) and better functional status (odds ratio, 8.09 [3.24-22.38]; P<0.0001). Conclusions- This study suggests that maintenance therapy with an immunosuppressant combined with glucocorticoids lead to the best long-term clinical and functional outcomes in patients with primary central nervous system vasculitis after having achieved remission with either glucocorticoids alone or in combination with another immunosuppressant.

Background and Purpose: Efficacy of endovascular treatment (EVT) for ischemic stroke because of large vessel occlusion may depend on patients' age and stroke severity; we, therefore, developed a prognosis score based on these variables and examined whether EVT efficacy differs between patients with good, intermediate, or poor prognostic score., Methods: A total of 4079 patients with an acute ischemic stroke were identified from the Paris Stroke Consortium registry. We developed the stroke checkerboard (SC) score (SC score=1 point per decade ≥50 years of age and 2 points per 5 points on the National Institutes of Health Stroke Scale) to predict spontaneous outcome. The primary outcome was the adjusted common odds ratio for an improvement in the modified Rankin Scale at 90 days after EVT, in patients with low, intermediate, or high SC scores. To rule out potential selection biases, a nested case-control analysis, with individual matching for all major prognostic factors, was also performed, to compare patients with large vessel occlusion in the anterior circulation treated or not with EVT., Results: In patients untreated with EVT, SC scores <8 were predictive of good outcomes (modified Rankin Scale score, 0-2; area under the curve, 0.87), whereas SC scores >12 were predictive of poor outcomes (modified Rankin Scale score, 4-6; area under the curve, 0.88). In the overall population, there was an interaction between EVT and prognosis group ( P <0.001). EVT was associated with improved outcome in patients with SC scores >12 (common odds ratio, 1.70; 95% confidence interval, 1.13-2.56) and SC scores 8 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.69) but not in patients with SC scores <8 (odds ratio, 0.72; 95% confidence interval, 0.56-0.93). Similar results were obtained in the case-control analysis among 449 patients treated with EVT and 449 matched patients untreated with EVT., Conclusions: In patients stratified with the SC score, EVT was associated with improved functional outcome in older and more severe patients but not in younger and less severe patients., (© 2018 American Heart Association, Inc.)

Background and Purpose: Stroke patients with large diffusion-weighted imaging (DWI) volumes are often excluded from reperfusion because of reckoned futility. In those with DWI volume >70 mL, included in the THRACE trial (Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke), we report the associations between baseline parameters and outcome., Methods: We examined 304 patients with anterior circulation stroke and pretreatment magnetic resonance imaging. Variables were extracted from the THRACE database, and DWI volumes were measured semiautomatically., Results: Among 53 patients with DWI volume >70 mL, 12 had favorable outcome (modified Rankin Scale score, ≤2) at 3 months; they had less coronary disease (0/12 versus 12/38; P =0.046) and less history of smoking (1/10 versus 12/31; P =0.013) than patients with modified Rankin Scale score >2. None of the 8 patients >75 years of age reached modified Rankin Scale score ≤2. Favorable outcome occurred in 12 of 37 M1-occluded patients but in 0 of 16 internal carotid-T/L-occluded patients ( P =0.010). Favorable outcome was more frequent (6/13) when DWI lesion was limited to the superficial middle cerebral artery territory than when it extended to the deep middle cerebral artery territory (6/40; P =0.050)., Conclusions: Stroke patients with DWI lesion >70 mL may benefit from reperfusion therapy, especially those with isolated M1 occlusion or ischemia restricted to the superficial middle cerebral artery territory. The benefit of treatment seems questionable for patients with carotid occlusion or lesion extending to the deep middle cerebral artery territory., (© 2018 American Heart Association, Inc.)

Background and Purpose: To evaluate hyperacute management of pediatric arterial ischemic stroke, setting up dedicated management pathways is the first recommended step to prove the feasibility and safety of such treatments. A regional pediatric stroke alert protocol including 2 centers in the Paris-Ile-de-France area, France, was established., Methods: Consecutive pediatric patients (28 days-18 years) with confirmed arterial ischemic stroke who had acute recanalization treatment (intravenous r-tPA [recombinant tissue-type plasminogen activator], endovascular procedure, or both) according to the regional pediatric stroke alert were retrospectively reviewed during a 40-month period., Results: Thirteen children, aged 3.7 to 16.6 years, had recanalization treatment. Median time from onset to magnetic resonance imaging was 165 minutes (150-300); 9 out of 13 had large-vessel occlusion. Intravenous r-tPA was used in 11 out of 13 patients, with median time from onset to treatment of 240 minutes (178-270). Endovascular procedure was performed in patients time-out for intravenous r-tPA (n=2) or after intravenous r-tPA inefficiency (n=2). No intracranial or peripheral bleeding was reported. One patient died of malignant stroke; outcome was favorable in 11 out of 12 survivors (modified Rankin Scale score 0-2)., Conclusions: Hyperacute recanalization treatment in pediatric stroke, relying on common protocols and adult/pediatric ward collaboration, is feasible. Larger systematic case collection is encouraged., (© 2017 American Heart Association, Inc.)

Background and Purpose: Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort., Methods: Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data., Results: Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P =0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively., Conclusions: Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic manifestations., (© 2017 American Heart Association, Inc.)

Background and Purpose: Early neurological deterioration (END) after anterior circulation stroke is strongly associated with poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END occurring after intravenous thrombolysis remains unclear in most instances. We tested the hypothesis that unexplained END is associated with thrombus extension., Methods: From our database of consecutively thrombolysed patients, we identified anterior circulation stroke patients who had both admission and 24-hour T2* magnetic resonance imaging, visible occlusion on admission magnetic resonance angiography and no recanalization on 24-hour magnetic resonance angiography. END was defined as ≥4 National Institutes of Health Stroke Scale-point deterioration on 24-hour clinical assessment and unexplained END as END without clear cause. The incidence of susceptibility vessel sign extension on T2* imaging, defined as any new occurrence or extension of susceptibility vessel sign from admission to 24-hour follow-up magnetic resonance, was compared between patients with unexplained END and those without END., Results: Of 120 eligible patients for the present study, 22 experienced unexplained END. Susceptibility vessel sign extension was present in 41 (34%) patients and was significantly more frequent in the unexplained END than in the no-END group (59% versus 29%, respectively; adjusted odds ratio=3.96; 95% confidence interval, 1.25-12.53; P=0.02)., Conclusions: In this study, unexplained END occurring after thrombolysis was independently associated with susceptibility vessel sign extension, suggesting in situ thrombus extension or re-embolization. These findings strengthen the need to further investigate early post-thrombolysis administration of antithrombotics to reduce the risk of this ominous clinical event., (© 2016 American Heart Association, Inc.)

Background and Purpose: Rapid and reliable assessment of the perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch is required to promote its wider application in both acute stroke clinical routine and trials. We tested whether an evaluation based on the Alberta Stroke Program Early CT Score (ASPECTS) reliably identifies the PWI/DWI mismatch., Methods: A total of 232 consecutive patients with acute middle cerebral artery stroke who underwent pretreatment magnetic resonance imaging (PWI and DWI) were retrospectively evaluated. PWI-ASPECTS and DWI-ASPECTS were determined blind from manually segmented PWI and DWI volumes. Mismatch-ASPECTS was defined as the difference between PWI-ASPECTS and DWI-ASPECTS (a high score indicates a large mismatch). We determined the mismatch-ASPECTS cutoff that best identified the volumetric mismatch, defined as VolumeTmax>6s/VolumeDWI≥1.8, a volume difference≥15 mL, and a VolumeDWI<70 mL., Results: Inter-reader agreement was almost perfect for PWI-ASPECTS (κ=0.95 [95% confidence interval, 0.90-1]), and DWI-ASPECTS (κ=0.96 [95% confidence interval, 0.91-1]). There were strong negative correlations between volumetric and ASPECTS-based assessments of DWI lesions (ρ=-0.84, P<0.01) and PWI lesions (ρ=-0.90, P<0.01). Receiver operating characteristic curve analysis showed that a mismatch-ASPECTS ≥2 best identified a volumetric mismatch, with a sensitivity of 0.93 (95% confidence interval, 0.89-0.98) and a specificity of 0.82 (95% confidence interval, 0.74-0.89)., Conclusions: The mismatch-ASPECTS method can detect a true mismatch in patients with acute middle cerebral artery stroke. It could be used for rapid screening of patients with eligible mismatch, in centers not equipped with ultrafast postprocessing software., (© 2016 American Heart Association, Inc.)

Background and Purpose: We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system., Methods: We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort., Results: The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], P<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12-130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification., Conclusions: Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide., (© 2016 American Heart Association, Inc.)

Objective: The aim of this study was to evaluate the safety profile of gadoterate meglumine from clinical trials, postmarketing observational studies, and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years of clinical use and over 50 million administered doses., Materials and Methods: Assessment of the safety of gadoterate meglumine through processing and review of all safety data was collected after magnetic resonance imaging procedures. All ADRs originated from 3 major sources: (1) a clinical study database including 50 phase I to IV studies involving 2822 patients, (2) a safety database including 8 postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a pharmacovigilance database compiling safety experience following over 50 million doses administered between March 1989 and September 2015., Results: Among the 2822 patients receiving gadoterate meglumine in the clinical trials, 241 (8.5%) experienced 405 postinjection adverse events (AEs), considered related to the contrast agent for 113 patients (4.0%). Serious AEs were reported for 27 patients (1.0%) and assessed as related to gadoterate meglumine for 2 patients (0.07%). None of the PMS studies showed evidence of unexpected safety issues, with a very low rate of AEs (<1%). Postmarketing safety experience with over 50 million doses of gadoterate meglumine prescribed for 25 years of approved use worldwide compiled spontaneous reports for 3797 patients who experienced 8397 ADRs, yielding a very low reported incidence of ADRs of 0.007% of patients. There was no single-agent case of confirmed nephrogenic systemic fibrosis with gadoterate meglumine either from clinical development programs or from postmarketing experience., Conclusions: Based on clinical trials, postmarketing observational studies and pharmacovigilance data, a very low incidence of ADRs was reported with gadoterate meglumine, which has no impact on its favourable benefit-risk ratio.

Background and Purpose: It remains debated whether clinical scores can help identify acute ischemic stroke patients with large-artery occlusion and hence improve triage in the era of thrombectomy. We aimed to determine the accuracy of published clinical scores to predict large-artery occlusion., Methods: We assessed the performance of 13 clinical scores to predict large-artery occlusion in consecutive patients with acute ischemic stroke undergoing clinical examination and magnetic resonance or computed tomographic angiography ≤6 hours of symptom onset. When no cutoff was published, we used the cutoff maximizing the sum of sensitivity and specificity in our cohort. We also determined, for each score, the cutoff associated with a false-negative rate ≤10%., Results: Of 1004 patients (median National Institute of Health Stroke Scale score, 7; range, 0-40), 328 (32.7%) had an occlusion of the internal carotid artery, M1 segment of the middle cerebral artery, or basilar artery. The highest accuracy (79%; 95% confidence interval, 77-82) was observed for National Institute of Health Stroke Scale score ≥11 and Rapid Arterial Occlusion Evaluation Scale score ≥5. However, these cutoffs were associated with false-negative rates >25%. Cutoffs associated with an false-negative rate ≤10% were 5, 1, and 0 for National Institute of Health Stroke Scale, Rapid Arterial Occlusion Evaluation Scale, and Cincinnati Prehospital Stroke Severity Scale, respectively., Conclusions: Using published cutoffs for triage would result in a loss of opportunity for ≥20% of patients with large-artery occlusion who would be inappropriately sent to a center lacking neurointerventional facilities. Conversely, using cutoffs reducing the false-negative rate to 10% would result in sending almost every patient to a comprehensive stroke center. Our findings, therefore, suggest that intracranial arterial imaging should be performed in all patients with acute ischemic stroke presenting within 6 hours of symptom onset., (© 2016 American Heart Association, Inc.)

Background and Purpose: Whether to withhold recanalization treatment when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is unsettled. Our aim was to assess the impact of recanalization on outcome in patients with baseline DWI lesion ≥70 mL (DWI≥70 mL) treated ≤4.5 hours from onset. We hypothesized that recanalization is beneficial in a sizeable fraction of these patients and that this is associated with a larger DWI lesion reversal., Methods: We analyzed 267 consecutive patients treated with intravenous recombinant tissue-type plasminogen activator for middle cerebral artery territory stroke in whom an occlusion was present on magnetic resonance angiography and 24-hour recanalization and 90-day clinical outcome could be assessed. After stratification relative to the 70-mL DWI lesion cut point, we calculated the odds ratio for recanalization of the primary arterial occlusive lesion (AOL score ≥2) to predict favorable outcome (modified Rankin scale score ≤2). DWI lesion reversal was compared between recanalizers with DWI≥70 mL with favorable and unfavorable outcomes., Results: Median (interquartile range) DWI lesion volume was 22 mL (10-60), and median onset time to imaging was 116 minutes (86-151). Twelve (22%) of the 54 patients with DWI≥70 mL experienced favorable outcome, of which 9 had recanalized. In patients with DWI≥70 mL, recanalization was significantly associated with favorable outcome after adjustment for age and National Institutes of Health Stroke Scale (odds ratio =4.72 [1.09-20.32]; P=0.0375). Among recanalizers with DWI≥70 mL, absolute and relative DWI reversal volumes were larger in those with favorable as compared with unfavorable outcome (18.8 mL [12.2-47.6] versus 8.5 mL [4.3-31.1]; P=0.17; and 19.6% [10.9-62.8] versus 8.7% [3.9-16.5], respectively; P=0.049)., Conclusions: Patients with DWI lesion volume ≥70 mL can benefit from recanalization after intravenous recombinant tissue-type plasminogen activator. This may partly reflect a larger amount of DWI lesion reversal., (© 2016 American Heart Association, Inc.)

Background and Purpose: Fluid-attenuated inversion recovery vascular hyperintensities (FVH) beyond the boundaries of diffusion-weighted imaging (DWI) lesion (FVH-DWI mismatch) have been proposed as an alternative to perfusion-weighted imaging (PWI)-DWI mismatch. We aimed to establish whether FVH-DWI mismatch can identify patients most likely to benefit from recanalization., Methods: FVH-DWI mismatch was assessed in 164 patients with proximal middle cerebral artery occlusion before intravenous thrombolysis. PWI-DWI mismatch (PWITmax>6sec/DWI>1.8) was assessed in the 104 patients with available PWI data. We tested the associations between 24-hours complete recanalization on magnetic resonance angiography and 3-month favorable outcome (modified Rankin Scale score ≤2), stratified on FVH-DWI (or PWI-DWI) status., Results: FVH-DWI mismatch was present in 121/164 (74%) patients and recanalization in 50/164 (30%) patients. The odds ratio for favorable outcome with recanalization was 16.2 (95% confidence interval, 5.7-46.5; P<0.0001) in patients with FVH-DWI mismatch and 2.6 (95% confidence interval, 0.6-12.1; P=0.22) in those without FVH-DWI mismatch (P=0.048 for interaction). Recanalization was associated with favorable outcome in patients with PWI-DWI mismatch (odds ratios, 9.9; 95% confidence interval, 3.1-31.3; P=0.0001) and in patients without PWI-DWI mismatch (odds ratios, 7.0; 95% confidence interval, 1.1-44.1; P=0.047), P=0.76 for interaction., Conclusion: The FVH-DWI mismatch may rapidly identify patients with proximal occlusion most likely to benefit from recanalization., (© 2016 American Heart Association, Inc.)

Background and Purpose: Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement (CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms., Methods: We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present., Results: We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (κ=0.85; 95% confidence interval, 0.75-0.95 and κ=0.90; 95% confidence interval, 0.83-0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92-29.0; P=0.0002)., Conclusions: CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall., (© 2014 American Heart Association, Inc.)

Background and Purpose: Childhood intracerebral hemorrhage is mainly attributable to underlying brain arteriovenous malformations (bAVMs). Multimodal treatment options for bAVMs include microsurgery and embolization, allowing an immediate cure, and radiosurgery, entailing longer obliteration times. Follow-up data on pediatric ruptured bAVMs are scarce, making it difficult to assess the risk of subsequent intracerebral hemorrhage. Our aim was to assess the clinical and angiographic outcome and to analyze risk factors for rebleeding during and after combined treatment of pediatric bAVMs., Methods: A prospectively maintained database of children referred to our institution between January 1997 and October 2012 for bAVMs was retrospectively queried to identify all consecutive ruptured bAVMs treated by surgery, embolization, and radiosurgery. The impact of baseline clinical and bAVM characteristics on clinical outcome, rebleeding rate, annual bleeding rate, and bAVM obliteration was studied using univariate and multivariate Cox regression analysis., Results: One hundred six children with ruptured bAVMs were followed up for a total of 480.5 patient-years (mean, 4.5 years). Thirteen rebleeding events occurred, corresponding to an annual bleeding rate of 2.71±1.32%, significantly higher in the first year (3.88±1.39%) than thereafter (2.22±1.38%; P<0.001) and in the case of associated aneurysms (relative risk, 2.68; P=0.004) or any deep venous drainage (relative risk, 2.97; P=0.002), in univariate and multivariate analysis. Partial embolization was associated with a higher annual bleeding rate, whereas initial surgery for intracerebral hemorrhage evacuation was associated with a lower risk of rebleeding., Conclusions: Associated aneurysms and any deep venous drainage are independent risk factors for rebleeding in pediatric ruptured bAVMs. Immediate surgery or total embolization might be advantageous for children harboring such characteristics, whereas radiosurgery might be targeted at patients without such characteristics., (© 2014 American Heart Association, Inc.)

Background and Purpose: The extent of diffusion lesion on pretreatment imaging is a risk factor for poor outcome and hemorrhagic transformation after thrombolysis, and volumes of 70 to 100 mL have been advocated as cut-offs. However, estimating diffusion-weighted imaging (DWI) lesion volume (VolDWI) in the acute setting may be cumbersome. We aimed to determine whether the DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) can substitute for VolDWI., Methods: DWI-ASPECTS and VolDWI were measured retrospectively on pretreatment MRI (median onset-to-MRI delay=122 minutes) in 330 consecutively treated patients with middle cerebral artery stroke., Results: DWI-ASPECTS and VolDWI were strongly correlated (ρ=-0.82), but each DWI-ASPECTS point corresponded to a wide range of VolDWI. All patients with DWI-ASPECTS≥7 (n=207) had VolDWI<70 mL, whereas 32 of the 34 patients with DWI-ASPECTS<4 had VolDWI>100 mL. However, intermediate DWI-ASPECTS (4-6; n=89) corresponded to highly variable VolDWI (median, 66 mL; interquartile range, 40-98)., Conclusions: Although each DWI-ASPECTS point corresponds to a wide range of volumes, DWI-ASPECTS<4 or ≥7 may be used as reliable surrogates of VolDWI>100 or <70 mL, respectively.

Background and Purpose: To propose a T2*-MR adaptation of the computed tomography angiography-clot burden score (CBS), and assess its value as predictor of 24-hour recanalization and clinical outcome in anterior circulation stroke treated by intravenous thrombolysis ≤4.5 hours from onset., Methods: Two independent observers retrospectively analyzed pretreatment T2* images for evaluation of clot burden, using a 10-point scale T2*-CBS. Three points are subtracted for susceptibility vessel sign in the supraclinoid internal carotid artery, 2 points each for susceptibility vessel sign in the proximal and distal part of middle cerebral artery, and 1 point each for susceptibility vessel sign in middle cerebral artery branches (with a maximum of 2 points) and for susceptibility vessel sign in anterior cerebral artery. Associations with 24-hour recanalization and favorable outcome (3-month modified Rankin Scale score, ≤2) were assessed in multivariate analyses., Results: We analyzed 184 consecutive patients (mean age, 67 years) with median (interquartile range) admission National Institutes of Health Stroke Scale score and onset-to-treatment time of 15 (9-19) and 151 (120-185) minutes, respectively. The intraclass correlation for T2*-CBS between observers was 0.97 (95% confidence interval, 0.97-0.98). In multivariate analyses, T2*-CBS >6 was significantly associated with 24-hour recanalization (adjusted odds ratio, 5.1 [1.9-13.5]; P=0.001) or with favorable outcome (adjusted odds ratio, 4.2 [1.7-10.8]; P=0.003)., Conclusions: T2*-CBS, a new reproducible semiquantitative score adapted from the computed tomography angiography-CBS, is associated with 24-hour recanalization and 3-month outcome after intravenous thrombolysis. This score needs external validation and could be useful to identify poor responders to intravenous thrombolysis.

Background and Purpose: The DRAGON score, which includes clinical and computed tomographic scan parameters, showed a high specificity to predict 3-month outcome in patients with acute ischemic stroke treated by intravenous tissue plasminogen activator. We adapted the score for patients undergoing MRI as the first-line diagnostic tool., Methods: We reviewed patients with consecutive anterior circulation ischemic stroke treated ≤ 4.5 hour by intravenous tissue plasminogen activator between 2003 and 2012 in our center, where MRI is systematically implemented as first-line diagnostic work-up. We derived the MRI-DRAGON score keeping all clinical parameters of computed tomography-DRAGON (age, initial National Institutes of Health Stroke Scale and glucose level, prestroke handicap, onset to treatment time), and considering the following radiological variables: proximal middle cerebral artery occlusion on MR angiography instead of hyperdense middle cerebral artery sign, and diffusion-weighted imaging Alberta Stroke Program Early Computed Tomography Score (DWI ASPECTS) ≤ 5 instead of early infarct signs on computed tomography. Poor 3-month outcome was defined as modified Rankin scale >2. We calculated c-statistics as a measure of predictive ability and performed an internal cross-validation., Results: Two hundred twenty-eight patients were included. Poor outcome was observed in 98 (43%) patients and was significantly associated with all parameters of the MRI-DRAGON score in multivariate analysis, except for onset to treatment time (nonsignificant trend). The c-statistic was 0.83 (95% confidence interval, 0.78-0.88) for poor outcome prediction. All patients with a MRI-DRAGON score ≤ 2 (n=22) had a good outcome, whereas all patients with a score ≥ 8 (n=11) had a poor outcome., Conclusions: The MRI-DRAGON score is a simple tool to predict 3-month outcome in acute stroke patients screened by MRI then treated by intravenous tissue plasminogen activator and may help for therapeutic decision.

Background and Purpose: It is unclear whether strokes in patients with spontaneous cervical artery dissection (CAD) are due to secondary thromboembolism or to a reduction in cerebral blood flow from the primary cervical lesion. The aim of this study was to identify the most likely mechanism of stroke using cervical and cerebral imaging parameters in patients with CAD., Methods: The study was approved by the local Ethics Committee. Informed consent was waived. We retrospectively evaluated the cerebrovascular ultrasound, cervical MR angiography, and stroke brain MRI in consecutive patients with CAD. An embolic mechanism was considered in the case of direct visualization of an intracranial embolism as a susceptibility vessel sign on T2* or in the case of pial artery territory infarction on diffusion-weighted imaging. A hemodynamic mechanism was considered in the case of watershed infarction and in the case of an association of watershed infarction and pial artery territory infarction when ≥ 2 of the following were present: severe stenotic or occlusive CAD, reduced intracranial velocity on cerebrovascular ultrasound or signal on MR angiography, or hyperintense vessel sign on fluid-attenuated inversion recovery. The remaining patients were considered to have a mixed mechanism., Results: Of 172 consecutive patients with CAD, 100 (58%) had acute stroke on diffusion-weighted imaging. Stroke was attributed to a thromboembolic mechanism in 85 of 100 patients, a hemodynamic mechanism in 12 of 100 patients, and a mixed mechanism in 3 of 100 patients., Conclusions: Stroke in patients with CAD is most frequently associated with both direct and indirect signs of artery-to-artery embolization on imaging, a finding that should help design future therapeutic trials.

Background and Purpose: In stroke attributable to spontaneous dissection of the cervical artery, it is unclear whether the occurrence and pattern of stroke depend on the degree of stenosis., Methods: In 147 consecutive dissection of the cervical artery patients with (n=88) and without stroke (n=59), we compared the number, volume, and patterns of cerebral diffusion-weighted imaging stroke lesions among patients with <70% stenosis (Group 1), ≥70% stenosis (Group 2), and occlusion (Group 3)., Results: The presence (26 of 45 in Group 1, 32 of 59 in Group 2, 30 of 43 in Group 3; P=0.27) and the number of diffusion-weighted imaging lesions (mean±SD [interquartile range], 3.5±3.9 [1-4] in Group 1; 4.2±4.1 [1-5] in Group 2; 3.3±4.0 [1-3] in Group 3; P=0.85) were independent of lumen patency, whereas volume of diffusion-weighted imaging lesions was larger in occlusive dissection of the cervical artery (82±90 mm [17-91] versus 34±54 [2-48]; P=0.03). There were no differences in the breakdown of diffusion-weighted imaging lesion patterns according to degree of stenosis., Conclusions: The occurrence and diffusion-weighted imaging lesion patterns in dissection of the cervical artery patients may not be influenced by the degree of stenosis of the dissected artery. Occlusive dissection of the cervical artery was associated with larger infarcts.

Objective: Intraplaque hemorrhage (IPH) is an emerging marker of plaque instability. However, little is known about the relationships between IPH and traditional risk factors and whether these relationships differ between symptomatic and asymptomatic disease., Methods and Results: Two hundred thirty-four patients with symptomatic (n=114) or asymptomatic (n=120) carotid stenosis underwent high-resolution plaque magnetic resonance imaging. Seventy-five patients had recent IPH (symptomatic, 33%; asymptomatic, 31%). In symptomatic stenosis, recent IPH was independently associated with degree of stenosis (odds ratio [OR]=4.21, 1.61-10.98 for North American Symptomatic Carotid Endarterectomy Trial >35%; OR=2.92, 1.18-7.24 for European Carotid Surgery Trial >60%), qualifying event (OR=4.13; 1.11-15.32 for stroke or hemispheric transient ischemic attack ≥1 hour versus transient ischemic attack <1 hour or ocular symptoms), time from ischemic event (OR=6.65, 1.56-28.35 for ≤2 weeks; OR=2.24, 0.87-5.81 for 2-12 weeks versus >12 weeks; P for trend=0.03). In asymptomatic stenosis, IPH was only associated with stenosis severity >70% by ECST (OR=6.65; 1.95-22.73) but not by the NASCET method., Conclusions: Our findings support the potential link between recent IPH and risk of ipsilateral stroke in symptomatic disease but also imply that prognostic studies should adjust for known stroke risk factors in multivariate analyses. In asymptomatic stenosis, the potential predictive value of recent IPH is less likely to be confounded by stroke risk factors.