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.).

Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke.

BACKGROUND: Performing endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) allows a port of entry for intracranial biological sampling. OBJECTIVE: To test the hypothesis that specific immune players are molecular contributors to disease, outcome biomarkers, and potential targets for modifying AIS. METHODS: We examined 75 subjects presenting with large vessel occlusion of the anterior circulation and undergoing EVT. Intracranial blood samples were obtained by microcatheter aspiration, as positioned for stent deployment. Peripheral blood samples were collected from the femoral artery. Plasma samples were quality controlled by electrophoresis and analyzed using a Mesoscale multiplex for targeted inflammatory and vascular factors. RESULTS: We measured 37 protein biomarkers in our sample cohort. Through multivariate analysis, adjusted for age, intravenous thrombolysis, pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT scores, we found that post-clot blood levels of interleukin-6 (IL-6) were significantly correlated (adjusted P value <0.05) with disability assessed by the modified Rankin Scale (mRS) score at 90 days, with medium effect size. Chemokine (C-C) ligand 17 CCL17/TARC levels were inversely correlated with the mRS score. Examination of peripheral blood showed that these correlations did not reach statistical significance after correction. Intracranial biomarker IL-6 level was specifically associated with a lower likelihood of favorable outcome, defined as a mRS score of 0-2. CONCLUSIONS: Our findings show a signature of blood inflammatory factors at the cerebrovascular occlusion site. The correlations between these acute-stage biomarkers and mRS score outcome support an avenue for add-on and localized immune modulatory strategies in AIS.

Endovascular therapy of acute vertebrobasilar occlusions: influence of first-line strategy in the Endovascular Treatment in Ischemic Stroke (ETIS) Registry.

BACKGROUND: The choice of the first-line technique in vertebrobasilar occlusions (VBOs) remains challenging. We aimed to report outcomes in a large cohort of patients and to compare the efficacy and safety of contact aspiration (CA) and combined technique (CoT) as a first-line endovascular technique in patients with acute VBOs. METHODS: We retrospectively analyzed clinical and neuroradiological data of patients with VBOs from the prospective, multicenter, observational Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and August 2023. The primary outcome was the first pass effect (FPE) rate, whereas modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3 and 2c-3, number of passes, need for rescue strategy, modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage (sICH) were secondary outcomes. We performed univariate and multivariate analyses to investigate differences between the two groups. RESULTS: Among the 583 included patients (mean age 66.2 years, median National Institutes of Health Stroke Scale (NIHSS) 13, median posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) 8), 393 were treated with CA alone and 190 with CoT. Procedures performed with CA were shorter compared with CoT (28 vs 47 min, P<0.0001); however, no differences were observed in terms of FPE (CA 43.3% vs CoT 38.4%, P=0.99), and successful final recanalization (mTICI 2b-3, CA 92.4% vs CoT 91.8%, P=0.74) did not differ between the two groups. Functional independence and sICH rates were also similar, whereas mortality was significantly lower in the CA group (34.5% vs 42.9%; OR 1.79, 95% CI 1.03 to 3.11). CONCLUSIONS: We observed no differences in FPE, mTICI 2b-3, sICH, and functional independence between the two study groups. First-line CA was associated with shorter procedures and lower mortality rates than CoT.

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.

Intravenous thrombolysis with tenecteplase versus alteplase combined with endovascular treatment of anterior circulation tandem occlusions: A pooled analysis of ETIS and TETRIS.

BACKGROUND: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment. PATIENTS AND METHODS: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed. RESULTS: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69). CONCLUSION: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials.

Combined Technique for Internal Carotid Artery Terminus or Middle Cerebral Artery Occlusions in the ASTER2 Trial.

BACKGROUND: The aim of this study was to report the results of a subgroup analysis of the ASTER2 trial (Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion) comparing the safety and efficacy of the combined technique (CoT) and stent retriever as a first-line approach in internal carotid artery (ICA) terminus±M1-middle cerebral artery (M1-MCA) and isolated M1-MCA occlusions. METHODS: Patients enrolled in the ASTER2 trial with ICA terminus±M1-MCA and isolated M1-MCA occlusions were included in this subgroup analysis. The effect of first-line CoT versus stent retriever according to the occlusion site was assessed on angiographic (first-pass effect, expanded Treatment in Cerebral Infarction score ≥2b50, and expanded Treatment in Cerebral Infarction score ≥2c grades at the end of the first-line strategy and at the end of the procedure) and clinicoradiological outcomes (24-hour National Institutes of Health Stroke Scale, ECASS-III [European Cooperative Acute Stroke Study] grades, and 3-month modified Rankin Scale). RESULTS: Three hundred sixty-two patients were included in the postsubgroup analysis according to the occlusion site: 299 were treated for isolated M1-MCA occlusion (150 with first-line CoT) and 63 were treated for ICA terminus±M1-MCA occlusion (30 with first-line CoT). Expanded Treatment in Cerebral Infarction score ≥2b50 (odds ratio, 11.83 [95% CI, 2.32-60.12]) and expanded Treatment in Cerebral Infarction score ≥2c (odds ratio, 4.09 [95% CI, 1.39-11.94]) were significantly higher in first-line CoT compared with first-line stent retriever in patients with ICA terminus±M1-MCA occlusion but not in patients with isolated M1-MCA. CONCLUSIONS: First-line CoT was associated with higher reperfusion grades in patients with ICA terminus±M1-MCA at the end of the procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03290885.

Location specific rupture risk of intracranial aneurysms: case of ophthalmic aneurysms.

BACKGROUND: Aneurysm location is a key element in predicting the rupture risk of an intracranial aneurysm. A common impression suggests that pure ophthalmic aneurysms are under-represented in ruptured intracranial aneurysms (RIAs). The purpose of this study was to specifically evaluate the risk of rupture of ophthalmic aneurysms compared with other aneurysm locations. METHODS: This multicenter study compared the frequency of ophthalmic aneurysms in a prospective cohort of RIAs admitted to 13 neuroradiology centers between January 2021 and March 2021, with a retrospective cohort of patients with unruptured intracranial aneurysms (UIAs) who underwent cerebral angiography at the same neuroradiology centers during the same time period. RESULTS: 604 intracranial aneurysms were included in this study (355 UIAs and 249 RIAs; mean age 57 years (IQR 49-65); women 309/486, 64%). Mean aneurysm size was 6.0 mm (5.3 mm for UIAs, 7.0 mm for RIAs; P<0.0001). Aneurysm shape was irregular for 37% UIAs and 73% RIAs (P<0.0001). Ophthalmic aneurysms frequency was 14.9% of UIAs (second most common aneurysm location) and 1.2% of RIAs (second least common aneurysm location; OR 0.07 (95% CI 0.02 to 0.23), P<0.0001). CONCLUSIONS: Ophthalmic aneurysms seem to have a low risk of rupture compared with other intracranial aneurysm locations. This calls for a re-evaluation of the benefit-risk balance when considering preventive treatment for ophthalmic aneurysms.

Longitudinal radiological follow-up of individual level non-ischemic cerebral enhancing lesions following endovascular aneurysm treatment.

BACKGROUND: Non-ischemic cerebral enhancing (NICE) lesions following aneurysm endovascular therapy are exceptionally rare, with unknown longitudinal evolution. OBJECTIVE: To evaluate the radiological behavior of individual NICE lesions over time. METHODS: Patients included in a retrospective national multicentric inception cohort were analyzed. NICE lesions were defined, using MRI, as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema, distributed in the vascular territory of the aneurysm treatment, with no other confounding disease. Lesion burden and the longitudinal behavior of individual lesions were assessed. RESULTS: Twenty-two patients were included, with a median initial lesion burden of 36 (IQR 17-54) on the first MRI scan. Of the 22 patients with at least one follow-up MRI scan, 16 (73%) had new lesions occurring mainly within the first 200 weeks after the date of the procedure. The median number of new lesions per MRI was 6 (IQR 2-16). Among the same 22 patients, 7 (32%) had recurrent lesions. The median persistent enhancement of a NICE lesion was 13 weeks (IQR 6-30). No factor was predictive of early regression of enhancement activity with lesion regression kinetics mainly being patient-dependent. CONCLUSIONS: The behavior of individual NICE lesions was found to be highly variable with an overall patient-dependent regression velocity.

ASPECTS evolution after endovascular successful reperfusion in the early and extended time window.

BACKGROUND: The Alberta Stroke Program Early CT scan Score (ASPECTS) is a reliable imaging biomarker of infarct extent on admission but the value of 24-hour ASPECTS evolution in day-to-day practice is not well studied, especially after successful reperfusion. We aimed to assess the association between ASPECTS evolution after successful reperfusion with functional and safety outcomes, as well as to identify the predictors of ASPECTS evolution. METHODS: We used data from an ongoing prospective multicenter registry. Stroke patients with anterior circulation large vessel occlusion treated with endovascular therapy (EVT) and achieved successful reperfusion (modified thrombolysis in cerebral ischemia (mTICI) 2b-3) were included. ASPECTS evolution was defined as one or more point decrease in ASPECTS at 24 hours. RESULTS: A total of 2366 patients were enrolled. In a fully adjusted model, ASPECTS evolution was associated with lower odds of favorable outcome (modified Rankin Scale (mRS) score 0-2) at 90 days (adjusted odds ratio (aOR) = 0.46; 95% confidence interval (CI) = 0.37-0.57). In addition, ASPECTS evolution was a predictor of excellent outcome (90-day mRS 0-1) (aOR = 0.52; 95% CI = 0.49-0.57), early neurological improvement (aOR = 0.42; 95% CI = 0.35-0.51), and parenchymal hemorrhage (aOR = 2.64; 95% CI, 2.03-3.44). Stroke severity, admission ASPECTS, total number of passes, complete reperfusion (mTICI 3 vs. mTICI 2b-2c) and good collaterals emerged as predictors of ASPECTS evolution. CONCLUSION: ASPECTS evolution is a strong predictor of functional and safety outcomes after successful endovascular therapy. Higher number of EVT attempts and incomplete reperfusion are associated with ASPECTS evolution at day 1.

Using deep learning for an automatic detection and classification of the vascular bifurcations along the Circle of Willis.

Most of the intracranial aneurysms (ICA) occur on a specific portion of the cerebral vascular tree named the Circle of Willis (CoW). More particularly, they mainly arise onto fifteen of the major arterial bifurcations constituting this circular structure. Hence, for an efficient and timely diagnosis it is critical to develop some methods being able to accurately recognize each Bifurcation of Interest (BoI). Indeed, an automatic extraction of the bifurcations presenting the higher risk of developing an ICA would offer the neuroradiologists a quick glance at the most alarming areas. Due to the recent efforts on Artificial Intelligence, Deep Learning turned out to be the best performing technology for many pattern recognition tasks. Moreover, various methods have been particularly designed for medical image analysis purposes. This study intends to assist the neuroradiologists to promptly locate any bifurcation presenting a high risk of ICA occurrence. It can be seen as a Computer Aided Diagnosis scheme, where the Artificial Intelligence facilitates the access to the regions of interest within the MRI. In this work, we propose a method for a fully automatic detection and recognition of the bifurcations of interest forming the Circle of Willis. Several neural networks architectures have been tested, and we thoroughly evaluate the bifurcation recognition rate.

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.

Temporal trends in results of endovascular treatment of anterior intracranial large cerebral vessel occlusion: A 7-year study.

BACKGROUND: Technical improvements in devices, changes in angiographic grading scales and various confounding factors have made difficult the detection of the temporal evolution of angiographic and clinical results after endovascular treatment (EVT) for acute ischemic Stroke (AIS). We analyzed this evolution in time using the Endovascular Treatment in Ischemic Stroke (ETIS) registry. MATERIALS AND METHODS: We analyzed the efficacy outcomes of EVT performed from January 2015 to January 2022, and modelized the temporal trends using mixed logistic regression models, further adjusted for age, intravenous thrombolysis prior to EVT, general anesthesia, occlusion site, balloon catheter use and the type of first-line EVT strategy. We assessed heterogeneity in temporal trends according to occlusion site, balloon catheter use, cardio embolic etiology, age (<80 years vs ⩾80 years) and first-line EVT strategy. RESULTS: Among 6104 patients treated from 2015 to 2021, the rates of successful reperfusion (71.1%-89.6%) and of complete first pass effect (FPE) (4.6%-28.9%) increase, whereas the rates of patients with >3 EVT device passes (43.1%-17.5%) and favorable outcome (35.8%-28.9%) decrease significantly over time. A significant heterogeneity in temporal trends in successful reperfusion according to the first-line EVT strategy was found (p-het = 0.018). The temporal trend of increasing successful reperfusion rate was only significant in patients treated with contact aspiration in first-line (adjusted overall effect p = 0.010). CONCLUSION: In this 7-year-old large registry of ischemic stroke cases treated with EVT, we observed a significant increase with time in the rate of recanalization whereas there was a tendency toward a decrease in the rate of favorable outcome over the same period.

What is a Challenging Clot? : A DELPHI Consensus Statement from the CLOTS 7.0 Summit.

BACKGROUND: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. METHODS: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot. RESULTS: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts. CONCLUSION: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT.

"National survey for preliminary evaluation of neuroradiological protocols in patients with infective endocarditis".

OBJECTIVES: The aim of this study was to identify imaging protocols in patients with infective endocarditis through a nationwide survey. METHODS: An electronic evolutionary survey was sent to interventional Neuroradiologists among neuroradiological centers, under the aegis of the Société Française de Neuroradiologie. Among 33 contacted centers, 25 completed the survey (21 universitary hospitals and 4 peripheric hospitals). RESULTS: Most of the centers (88%) used systematic imaging screening in IE patients. MRI was the first imaging method used in 66% of cases, while CT was used in 44%. When no IIA was detectable in CT-scan screening, 6 (54,54%) stopped investigations, while 9 (81,81%) continued with MRI exploration in case of hemorrhage, ischemia or enhancement. Sulcal hemorrhage on MRI was an indication of complementary DSA in 25 centers (100%). Regarding IIA characterization, 12 centers (48%) used systematic DSA, whereas for 10 centers (40%), DSA was conditioned by hemorrhage or patient status. CONCLUSION: We highlighted large variations in Neuroimaging exploration and follow-up of IE patients in real-world practices. Expert guidelines able to standardize practices are warranted to improve the management of this serious and often misdiagnosed pathology.

Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations.

BACKGROUND: The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is an all-inclusive pragmatic study comprising 2 randomized clinical trials (RCTs). Patients excluded from the RCTs are followed in parallel treatment and observation registries, allowing a comparison between RCT and registry patients. METHODS: The first randomized clinical trial (RCT-1) offers 1:1 randomized allocation of intervention versus conservative management for patients with arteriovenous malformation (AVM). The second randomized clinical trial (RCT-2) allocates 1:1 pre-embolization or no pre-embolization to surgery or radiosurgery patients judged treatable with or without embolization. Characteristics of RCT patients are reported and compared to registry patients. RESULTS: From June 2014 to May 2021, 1010 patients with AVM were recruited; 498 patients were observed and 373 were included in the treatment registries. Randomized allocation in RCT-1 was applied to 139 (26%) of the 512 patients (including 127 of 222 [57%] with unruptured AVMs) considered for curative treatment. RCT-1 AVM patients differed (in rupture status, Spetzler-Martin grade and baseline modified Rankin Score) from those in the observation or treatment registries (P < 0.001). Most patients had small (<3 cm; 71%) low-grade (Spetzler-Martin I-II; 64%) unruptured (91%) AVMs. The allocated management was conservative (n = 71) or curative (n = 68), using surgery (n = 39), embolization (n = 16), or stereotactic radiosurgery (n = 13). Pre-embolization was considered for 179/309 (58%) patients allocated/assigned to surgery or stereotactic radiosurgery; 87/179 (49%) were included in RCT-2. RCT-2 patient AVMs differed in size, eloquence and grade from patients of the pre-embolization registry (P < 0.01). Most had small (<3 cm in 82%) low-grade (83%) AVMs in non-eloquent brain (64%). CONCLUSIONS: Patients included in the RCTs differ significantly from registry patients. Meaningful results can be obtained if multiple centers actively participate in the TOBAS RCTs.

Risk Prediction of New Intracranial Aneurysms at Follow-Up Screening in People With a Positive Family History.

BACKGROUND: In first-degree relatives of patients with aneurysmal subarachnoid hemorrhage (aSAH), the risk of an intracranial aneurysm can be predicted at initial screening but not at follow-up screening. We aimed to develop a model for predicting the probability of a new intracranial aneurysm after initial screening in people with a positive family history of aSAH. METHODS: In a prospective study, we obtained data from follow-up screening for aneurysms of 499 subjects with ≥2 affected first-degree relatives. Screening took place at the University Medical Center Utrecht, the Netherlands, and the University Hospital of Nantes, France. We studied associations between potential predictors and the presence of aneurysms using Cox regression analysis and the predictive performance at 5, 10, and 15 years after initial screening using C statistics and calibration plots, while correcting for overfitting. RESULTS: In 5050 person-years of follow-up, intracranial aneurysms were found in 52 subjects. The risk of aneurysm at 5 years was 2% to 12%, at 10 years, 4% to 28%, and at 15 years, 7% to 40%. Predictors were female sex, history of intracranial aneurysms/aneurysmal subarachnoid hemorrhage, and older age. The sex, previous history of intracranial aneurysm/aSAH, older age score had a C statistic of 0.70 (95% CI, 0.61-0.78) at 5 years, 0.71 (95% CI, 0.64-0.78) at 10 years, and 0.70 (95% CI, 0.63-0.76) at 15 years and showed good calibration. CONCLUSIONS: The sex, previous history of intracranial aneurysm/aSAH, older age score provides risk estimates for finding new intracranial aneurysms at 5, 10, and 15 years after initial screening, based on 3 easily retrievable predictors; this can help to define a personalized screening strategy after initial screening in people with a positive family history for aSAH.

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.

BACKGROUND: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. METHODS: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. RESULTS: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (ß=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). CONCLUSIONS: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Aspirin versus aggressive antiplatelet therapy for acute carotid stenting plus thrombectomy in tandem occlusions: ETIS Registry results.

BACKGROUND: Patients treated with acute carotid stenting (CAS) may have higher odds of a favorable outcome than those treated without CAS during thrombectomy in tandem occlusions. Antiplatelet therapy is associated with CAS to avoid stent thrombosis, which occurs in around 20% of patients and negatively impacts outcomes. In this study we compared two antiplatelet strategies in tandem occlusion strokes treated with CAS and intracranial thrombectomy in clinical practice. METHODS: The Endovascular Treatment in Ischemic Stroke Registry is an ongoing prospective observational study involving 21 comprehensive stroke centers performing thrombectomy in France. We analyzed patients with atherosclerotic tandem occlusions treated with acute CAS and intracranial thrombectomy who received at least one antiplatelet agent. Aggressive antiplatelet therapy included oral or intravenous glycoprotein (GP) IIb/IIIa or P2Y12 inhibitors. The primary outcome was cervical carotid artery patency at day 1 imaging follow-up. RESULTS: Among the 187 included patients, 124 (66.3%) received aspirin alone and 63 (33.7%) received aggressive antiplatelet therapy. There was no significant difference regarding safety outcomes, especially in symptomatic intracerebral hemorrhage, parenchymal hematoma, and procedural complications. There was a significantly higher rate of carotid stent patency at day 1 in the aggressive antiplatelet therapy group (81.7% vs 97.1%, aOR 17.49, 95% CI 1.10 to 277.2, p=0.042). Odds of favorable functional outcome (90-day modified Rankin Scale score 0-2) were similar between the groups (OR 3.04, 95% CI 0.64 to 14.25, p=0.158). CONCLUSIONS: In tandem occlusions treated with CAS plus thrombectomy, an aggressive antiplatelet regimen was associated with an increased rate of carotid stent patency at day 1 without safety concerns. Randomized trials are warranted to confirm these findings.

Influence of prior intravenous thrombolysis in patients treated with mechanical thrombectomy for M2 occlusions: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) registry.

BACKGROUND: Intravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone. METHODS: We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0-2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients. RESULTS: Among 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004). CONCLUSIONS: In cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These results suggest the benefit of IVT in patients undergoing MT for M2 occlusions.