Sotorasib for Vascular Malformations Associated with KRAS G12C Mutation.

KRAS gain-of-function mutations are frequently observed in sporadic arteriovenous malformations. The mechanisms underlying the progression of such KRAS-driven malformations are still incompletely understood, and no treatments for the condition are approved. Here, we show the effectiveness of sotorasib, a specific KRAS G12C inhibitor, in reducing the volume of vascular malformations and improving survival in two mouse models carrying a mosaic Kras G12C mutation. We then administered sotorasib to two adult patients with severe KRAS G12C-related arteriovenous malformations. Both patients had rapid reductions in symptoms and arteriovenous malformation size. Targeting KRAS G12C appears to be a promising therapeutic approach for patients with KRAS G12C-related vascular malformations. (Funded by the European Research Council and others.).

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.

Long-term clinical and ultrasound follow-up after transient perivascular inflammation of the carotid artery (TIPIC) syndrome: a multicenter study.

BACKGROUND: The present study aimed to describe the clinical and ultrasound (US) long-term follow-up of patients with transient perivascular inflammation of the carotid artery (TIPIC) syndrome and the risk of recurrence. METHODS: We enrolled patients with a definitive diagnosis of TIPIC syndrome who were included in a retrospective multicenter study. These patients were recontacted at least six months after the first TIPIC episode for a clinical and imaging follow-up. Each patient underwent a clinical evaluation through a tailored questionnaire as well as US imaging. RESULTS: Twenty-eight patients were enrolled with a median follow-up of 58.7 months (interquartile range = 8-121). Nineteen out of the 28 patients (67.8%) had residual pain, eight (28.6%) had experienced a clinical recurrence and 12 (42.9%) had a thickening of the carotid wall on US. No patients had neurological complication or other associated diseases. CONCLUSIONS: Patients with TIPIC syndrome have often residual pain and recurrence in about one quarter of cases but the long-term follow-up is in favor a benign self-limited pathology.Trial registration: ClinicalTrials.gov (identifier NCT03804112).

Gadolinium-enhanced intracranial aneurysm wall imaging and risk of aneurysm growth and rupture: a multicentre longitudinal cohort study.

OBJECTIVES: In patients with an unruptured intracranial aneurysm, gadolinium enhancement of the aneurysm wall is associated with growth and rupture. However, most previous studies did not have a longitudinal design and did not adjust for aneurysm size, which is the main predictor of aneurysm instability and the most important determinant of wall enhancement. We investigated whether aneurysm wall enhancement predicts aneurysm growth and rupture during follow-up and whether the predictive value was independent of aneurysm size. MATERIALS AND METHODS: In this multicentre longitudinal cohort study, individual patient data were obtained from twelve international cohorts. Inclusion criteria were as follows: 18 years or older with ≥ 1 untreated unruptured intracranial aneurysm < 15 mm; gadolinium-enhanced aneurysm wall imaging and MRA at baseline; and MRA or rupture during follow-up. Patients were included between November 2012 and November 2019. We calculated crude hazard ratios with 95%CI of aneurysm wall enhancement for growth (≥ 1 mm increase) or rupture and adjusted for aneurysm size. RESULTS: In 455 patients (mean age (SD), 60 (13) years; 323 (71%) women) with 559 aneurysms, growth or rupture occurred in 13/194 (6.7%) aneurysms with wall enhancement and in 9/365 (2.5%) aneurysms without enhancement (crude hazard ratio 3.1 [95%CI: 1.3-7.4], adjusted hazard ratio 1.4 [95%CI: 0.5-3.7]) with a median follow-up duration of 1.2 years. CONCLUSIONS: Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not independent of aneurysm size. CLINICAL RELEVANCE STATEMENT: Gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, since it appears to have no additional value to conventional predictors. KEY POINTS: • Although aneurysm wall enhancement is associated with aneurysm instability in cross-sectional studies, it remains unknown whether it predicts risk of aneurysm growth or rupture in longitudinal studies. • Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not when adjusting for aneurysm size. • While gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, it may hold potential for aneurysms smaller than 7 mm.

Cerebral embolic protection during transcatheter stent expansion of restrictive extra-cardiac Fontan conduit.

We report a 20-year-old female patient (76 Kg/164 cm) with an extra-cardiac Fontan circulation who was referred to our institution for exertional dyspnoea and desaturation. The patient was diagnosed with a large calcified thrombus at the level of the Fontan fenestration, protruding inside the lumen of the conduit and reducing the diameter by half with a 3 mmHg pressure gradient. Transcatheter stent expansion of the obstructed extra-cardiac conduit was done with a 48 mm long XXL PTFE-covered Optimus-CVS® under temporary cerebral embolic protection with a TriGUARD-3™ deflection filter device (Keystone Heart). There was no procedural complication and the 3 months clinical outcomes are good.

Impact of Day 1 carotid patency on outcome in dissection-related tandem occlusions treated with mechanical thrombectomy.

BACKGROUND: The clinical benefit of mechanical thrombectomy(MT) for stroke patients with tandem occlusion is similar to that of isolated intracranial occlusions. However, the management of cervical internal carotid artery(ICA) occlusion during the MT, particularly in the setting of carotid dissection, remains controversial. We aimed to investigate the clinical impact of cervical ICA patency at day 1 on 3-month functional outcome. METHODS: We collected data from the Endovascular Treatment in Ischemic Stroke, a prospective national registry in 30 French centers performing MT between January 2015 and January 2022. Inclusion criteria were consecutive tandem occlusions related to cervical ICA dissection treated with MT. Tandem occlusions of other etiology, isolated cervical ICA occlusions without intracranial thrombus and patients without day-1 ICA imaging were excluded. Primary endpoint was the 3-month functional outcome. Secondary endpoints included intracranial hemorrhage(ICH), excellent outcome, mortality and early neurological improvement. A sensitivity analysis was performed in patients with intracranial favorable recanalization after MT. RESULTS: During the study period, 137 patients were included of which 89(65%) presented ICA patency at day 1. The odds of favorable outcome did not significantly differ between patients with patent and occluded ICA at day 1(68.7 vs 59.1%;aOR=1.30;95%CI 0.56-3.00,p=0.54). Excellent outcome, early neurological improvement, mortality and ICH were also comparable between groups. Sensitivity analysis showed similar results. CONCLUSION: ICA patency at day 1 in patients with tandem occlusions related to dissection did not seem to influence functional outcome. Endovascular recanalization of the cervical ICA including stenting might not be systematically required in this setting.

Diffusion-Weighted Imaging Lesion Reversal in Older Patients With Stroke Treated With Mechanical Thrombectomy.

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.

Effects of weather conditions on endovascular treatment case volume for patients with ischemic stroke.

BACKGROUND: Weather conditions have been shown to influence the occurrence of cardiovascular events. We tested the hypothesis that weather parameters may be associated with variations of case volume of endovascular treatment (EVT) for acute ischemic stroke. METHODS: Individual data from the ETIS (Endovascular Treatment in Ischemic Stroke) French national registry were matched to local weather stations. Meteorological parameters (rainfall, humidity, atmospheric pressure, air temperature) were gathered from national online resources. Weather readings and EVT case volumes were annually standardized per weather station and EVT center, and their associations tested with non-parametric univariable and generalized linear statistical models. RESULTS: Between 2015 and 2021, 9913 EVT procedures addressed by 135 primary stroke units were matched to weather conditions. The mean daily case volume per center was 0.41 [StDev 0.33], and there was a median of 0.84 procedures daily linked to a weather station [StDev 0.47]. We found lower atmospheric pressure (ß estimate -0.04; 95%CI[-0.07;-0.03], p<0.001), higher humidity (ß estimate 0.07; 95%CI [0.05;0.09], p<0.001) and lower temperatures (ß estimate -0.08; 95%CI[-0.10;-0.06], p<0.001) to be associated with higher standardized EVT daily case volumes. These associations were stable when testing them across strata of binned EVT standardized case volumes. CONCLUSIONS: Our study suggests that lower ambient temperature, lower atmospheric pressure, and higher air humidity are associated with significantly more daily EVT cases in a European temperate country. These results may provide insight into both system of care optimization at times of climate change and intracranial LVO pathophysiology. REGISTRATION-URL: https://clinicaltrials.gov/ct2/show/NCT03776877.

Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

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.

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.

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.

Mechanical thrombectomy failure in anterior circulation strokes: Outcomes and predictors of favorable outcome.

BACKGROUND AND PURPOSE: Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure. METHODS: We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome. RESULTS: The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12-21) and 7 (IQR 5-8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94-0.98, p < 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83-0.91, p < 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77-0.87, p < 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71-0.98, p = 0.026) and stroke etiology [significant difference among etiological subtypes (p = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71-5.67)] were significantly associated with a 90-day favorable outcome. CONCLUSIONS: In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome.

Background: The Transient Perivascular Inflammation of the Carotid artery (TIPIC) syndrome is presumably a very rare disease characterized by a local transient inflammation of the tissue around the carotid artery. Its pathophysiology remains unknown. We performed an updated study of TIPIC syndrome cases in the setting of a multinational collaborative study. Methods: This study was conducted as an observational multinational retrospective individual patient level cohort study. Information from all known cases diagnosed with TIPIC syndrome in the literature (2005-2020) was collected after a semi-structured literature search of PubMed and Web of Science. We also collected unpublished information of patients from French, Swiss, and Italian vascular medicine or radiology departments. Results: A total of 72 patients were included and served for data analysis: 42 (58.3%) were women; the mean age was 47.9 (SD=11.4) years. Symptoms were unilateral in 92% of patients and 81.4% required pain killers. At baseline, irrespective of the imaging method used, the median thickness of the carotid lesions was 5 (Q1-Q3: 4-7; range: 2-11) mm and the median length of the lesion was 20 (Q1-Q3: 10-30; range: 3-50) mm. We found a positive linear correlation between thickness and length. At follow-up, the thickness of the carotid lesions decreased to a median of 2 (Q1-Q3: 1-3; range: 0-6) mm; the length decreased to a median 10 (Q1-Q3: 5-15; range: 0-41) mm. A linear correlation between baseline and follow-up values was observed for both thickness and length measurements. Symptoms disappeared after a median of 14 (Q1-Q3: 10-15) days. Thirteen patients experienced a recurrence after a median follow-up of 6 (Q1-Q3: 2-12) months. Conclusions: The present analysis elucidates clinical and sonographic characteristics of TIPIC syndrome, indicating the benign nature of this condition. A future international registry will study the long-term course of the disease.

Hyperacute Recanalization Strategies and Childhood Stroke in the Evidence Age.

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.

Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage.

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.

Effect of Operator's Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study.

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 (ß 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.

Thrombectomy Complications in Large Vessel Occlusions: Incidence, Predictors, and Clinical Impact in the ETIS Registry.

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.

Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results.

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.

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.