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

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

Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis.

INTRODUCTION: Recently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. METHODS: We conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0-2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0-3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0-2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). RESULTS: A total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0-3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73-8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22-0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. CONCLUSIONS: In this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients.

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.).

Mechanical thrombectomy in basilar artery occlusions: impact of first-line strategy as a function of the occlusion level.

BACKGROUND: Retrospective studies suggest the superiority of first-line contact aspiration (CA) thrombectomy over stent-retriever (SR) in basilar artery occlusions (BAO). We aimed to investigate the impact of first-line mechanical thrombectomy per the occlusion level, considering differences in stroke etiology prevalence between proximal and distal BAO. METHODS: A retrospective, multicentric analysis of the Endovascular Treatment in Ischemic Stroke Registry (ETIS) included consecutive BAO patients treated from January 2016 to May 2022. Patients were categorized into SR (±aspiration) and CA alone groups. Occlusion levels were determined through digital subtraction angiography. Favorable clinical outcome was defined as 90-day modified Rankin Scale (mRS) 0-3. RESULTS: A total of 380 patients were analyzed (251 CA alone, 129 SR±aspiration). Globally, first-line SR showed lower recanalization rates (89.1% vs 94.8%, OR=0.29, 95% CI 0.16 to 0.53; p<0.001) and worse clinical outcomes (mRS 0-3: 46.0% vs 52.2%, OR=0.62, 95% CI 0.44 to 0.87; p=0.006) compared with CA. In proximal occlusions, SR was significantly associated with poorer clinical outcomes (mRS 0-3: 20.9% vs 37.1%; OR=0.40, 95% CI 0.19 to 0.83; p=0.014) despite similar recanalization rates. Conversely, in distal occlusions there was no difference in clinical outcomes although recanalization rates were higher with CA (modified Thrombolysis in Cerebral Infarction score (mTICI 2b/3): 97.7% vs 91.7%; OR=0.17, 95% CI 0.05 to 0.66; p=0.01). CONCLUSIONS: In our BAO population, CA demonstrated better angiographic outcomes in middle and distal occlusions and better clinical outcomes in proximal occlusions. This translated into better angiographic and clinical results in the global study population. Clinical results were particularly influenced by the negative impact of SR on 90-day mRS, independently of recanalization rates in proximal BAO.

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

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

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.

Embolization of the middle meningeal artery for the prevention of chronic subdural hematoma recurrence in high-risk patients: a randomized controlled trial-the EMPROTECT study protocol.

BACKGROUND: Middle meningeal artery (MMA) embolization has been proposed as a treatment of chronic subdural hematoma (CSDH). The benefit of the procedure has yet to be demonstrated in a randomized controlled trial. We aim to assess the efficacy of MMA embolization in reducing the risk of CSDH recurrence 6 months after burr-hole surgery compared with standard medical treatment in patients at high risk of postoperative recurrence. METHODS: The EMPROTECT trial is a multicenter open label randomized controlled trial (RCT) involving 12 French centers. Adult patients (≥18 years) operated for CSDH recurrence or for a first episode with a predefined recurrence risk factor are randomized 1:1 to receive either MMA embolization within 7 days of the burr-hole surgery (experimental group) or standard medical care (control group). The number of patients to be included is 342. RESULTS: The primary outcome is the rate of CSDH recurrence at 6 months. Secondary outcomes include the rate of repeated surgery for a homolateral CSDH recurrence during the 6-month follow-up period, the rate of disability and dependency at 1 and 6 months, defined by a modified Rankin Scale (mRS) score ≥4, mortality at 1 and 6 months, total cumulative duration of hospital stay during the 6-month follow-up period, directly or indirectly related to the CSDH and embolization procedure-related complication rates. CONCLUSIONS: The EMPROTECT trial is the first RCT evaluating the benefit of MMA embolization as a surgical adjunct for the prevention of CSDH recurrence. If positive, this trial will have a significant impact on patient care. TRIAL REGISTRATION NUMBER: NCT04372147.

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).

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.

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.

Laser interstitial thermal therapy is effective and safe for the treatment of brain tumors in NF1 patients after cerebral revascularization for moyamoya angiopathy: a report on two cases.

Background: The co-occurrence of moyamoya vasculopathy and extra-optic pathway tumors is rare in neurofibromatosis type 1 (NF1), with only four cases described in the literature. Brain surgery in these patients may be challenging because of the risk of brain infarction after skin and dural incision. Given its percutaneous and minimally invasive nature, laser interstitial thermal therapy (LITT) is an ideal option for the treatment of brain tumors in these patients. Here, we report on two patients with NF1 and moyamoya syndrome (MMS) treated for a brain glioma with LITT, after cerebral revascularization. Cases: The first patient, with familial NF1, underwent bilateral indirect revascularization with multiple burr holes (MBH) for symptomatic MMS. Two years later, she was diagnosed with a left temporal tumor, with evidence of radiologic progression over 10 months. The second patient, also with familial NF1, developed unilateral MMS when he was 6 years old and was treated with MBH. At the age of 15 years, MRI showed a right cingular lesion, growing on serial MRIs. Both patients underwent LITT with no perioperative complications; they are progression free at 10 and 12 months, respectively, and the tumors have decreased in volume. Discussion: While the association of extra-optic neoplasm and moyamoya angiopathy is seldom reported in NF1, tumor treatment is challenging in terms of both avoiding stroke and achieving oncological control. Here, we show in 2 cases, that LITT could be a safe and effective option in these rare conditions.