Late-onset vascular complications of radiotherapy for primary brain tumors: a case-control and cross-sectional analysis.

PURPOSE: Radiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT). METHODS: We retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study. RESULTS: A total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%). CONCLUSIONS: Stroke prevalence is increased in long-surviving PBT patients treated with cranial RT. IMPLICATIONS FOR CANCER SURVIVORS: CV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.

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.

Persistent perfusion abnormalities at day 1 correspond to different clinical trajectories after stroke.

BACKGROUND: Perfusion abnormalities after thrombolysis are frequent within and surrounding ischemic lesions, but their relative frequency is not well known. OBJECTIVE: To describe the different patterns of perfusion abnormalities observed at 24 hours and compare the characteristics of the patients according to their perfusion pattern. METHODS: From our thrombolysis registry, we included 226 consecutive patients with an available arterial spin labeling (ASL) perfusion sequence at day 1. We performed a blinded assessment of the perfusion status (hypoperfusion-h, hyperperfusion-H, or normal-N) in the ischemic lesion and in the surrounding tissue. We compared the time course of clinical recovery, the rate of arterial recanalization, and hemorrhagic transformations in the different perfusion profiles. RESULTS: We identified seven different perfusion profiles at day 1. Four of these (h/h, h/H, H/H, and H/N) represented the majority of the population (84.1%). The H/H profile was the most frequent (34.5%) and associated with 3-month good outcome (modified Rankin Scale (mRS): 63.5%). Patients with persistent hypoperfusion within and outside the lesion (h/h, 12.4%) exhibited worse outcomes after treatment (mRS score 0-2: 23.8%) than other patients, were less frequently recanalized (40.7%), and had more parenchymal hematoma (17.8%). The h/H profile had an intermediate clinical trajectory between the h/h profile and the hyperperfused profiles. CONCLUSION: ASL hypoperfusion within the infarct and the surrounding tissue was associated with poor outcome. A more comprehensive view of the mechanisms in the hypoperfused surrounding tissue could help to design new therapeutic approaches during and after reperfusion therapies.

Poor clinical outcome despite successful basilar occlusion recanalization in the early time window: incidence and predictors.

BACKGROUND: Endovascular treatment (EVT) for basilar artery occlusions (BAO) is associated with a higher rate of futile recanalization compared with anterior circulation procedures. We aimed to identify the incidence and predictors of poor clinical outcome despite successful reperfusion in current clinical practice. METHODS: We used data from the ETIS (Endovascular Treatment in Ischemic Stroke) registry, a prospective multicenter observational registry of stroke treated with EVT in France. Patients undergoing EVT for acute BAO from January 2014 to May 2019 successfully treated within 8 hours from onset were included. Predictors of 90-day poor outcome (modified Rankin Scale (mRS) 4-6) were researched within patients with successful (modified Thrombolysis In Cerebral Infarction (mTICI 2b-3)) and excellent (mTICI 2c-3) reperfusion. RESULTS: Among 242 patients treated within 8 hours, successful reperfusion was achieved in 195 (80.5%) and excellent reperfusion in 120 (49.5%). Poor outcome was observed in 107 (54.8%) and 60 (50%) patients, respectively. In patients with successful early reperfusion, age, higher initial National Institutes of Health Stroke Scale (NIHSS) score, lower posterior circulation Alberta Stroke Programme Early CT Score (pc-ASPECTS), and absence of prior intravenous thrombolysis were independent predictors of poor outcome. The only treatment factor with an independent predictive value was first-pass mTICI 2b-3 reperfusion (adjusted OR 0.13, 95% CI 0.05 to 0.37, p<0.001). In patients with excellent early reperfusion, independent predictors were age, initial NIHSS score, first-pass mTICI 2c-3 reperfusion, and hemorrhagic transformation on post-interventional imaging. CONCLUSIONS: Early successful reperfusion with EVT occurred in 80.5% of patients, and the only treatment-related factor predictive of clinical outcome was first pass mTICI 2b-3 reperfusion. Further research is warranted to identify the optimal techniques and devices associated with first pass reperfusion in the posterior circulation.

Thrombectomy in basilar artery occlusions: impact of number of passes and futile reperfusion.

BACKGROUND: The number of mechanical thrombectomy (MT) passes is strongly associated with angiographic reperfusion as well as clinical outcomes in patients with anterior circulation ischemic stroke. However, these associations have not been analyzed in patients with basilar artery occlusion (BAO). We investigated the influence of the number of MT passes on the degree of reperfusion and clinical outcomes, and compared outcome after ≤3 passes versus >3 passes. METHODS: We used data from the prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry at 18 sites in France. Patients with BAO treated with MT were included. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 90 days. We fit mixed multiple regression models, with center as a random effect. RESULTS: We included 275 patients. Successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) was achieved in 88.4%, and 41.8% had a favorable outcome. The odds ratio for favorable outcome with each pass above 1 was 0.41 (95% CI 0.23 to 0.73) and for recanalization (mTICI 2b-3) it was 0.70 (95% CI 0.57 to 0.87). In patients with ≤3 passes, the rate of favorable outcome in recanalized versus non-recanalized patients was 50.5% versus 10.0% (p=0.001), while in those with >3 passes it was 16.7% versus 15.2% (p=0.901). CONCLUSIONS: We found that BAO patients had a significant relationship between the number of MT passes and both recanalization and favorable functional outcome. We further found that the benefit of recanalization in BAO patients was significant only when recanalization was achieved within three passes, encouraging at least three passes before stopping the procedure.

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.

Effect of intravenous thrombolysis before endovascular therapy on outcome according to collateral status: insight from the ETIS Registry.

BACKGROUND: It is unknown whether collateral status modifies the effect of pretreatment intravenous thrombolysis (IVT) on the outcomes of patients with large vessel occlusions treated with endovascular therapy (EVT). We aimed to assess whether collateral status modifies the effect of IVT on the outcomes of EVT in clinical practice. METHODS: We used data from the ongoing prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France. Patients with anterior circulation proximal large vessel occlusions treated with EVT within 6 hours of symptom onset were enrolled. Patients were divided into two groups based on pretreatment with IVT. The two groups were matched based on baseline characteristics. We tested the interaction between collateral status and IVT in unadjusted and adjusted models. RESULTS: A total of 1589 patients were enrolled in the study, of whom 55% received IVT. Using a propensity score matching method, 724 no IVT patients were matched to 549 IVT patients. In propensity score weighted analysis, IVT was associated with higher odds of early neurological improvement (OR 1.74; 95% CI 1.33 to 2.26), favorable functional outcome (OR 1.66; 95% CI 1.23 to 2.24), excellent functional outcome (OR 2.04; 95% CI 1.47 to 2.83), and successful reperfusion (OR 2.18; 95% CI 1.51 to 3.16). IVT was not associated with mortality or hemorrhagic complications. There was no interaction between collateral status and IVT association with any of the outcomes. CONCLUSIONS: Collateral status does not modify the effect of pretreatment IVT on the efficacy and safety outcomes of EVT.

Endovascular reperfusion of M2 occlusions in acute ischemic stroke reduced disability and mortality: ETIS Registry results.

BACKGROUND: The predictors of successful reperfusion and the effect of reperfusion after endovascular treatment (EVT) for M2 occlusions have not been well studied. We aimed to identify predictors of successful reperfusion and the effect of reperfusion on outcomes of EVT for M2 occlusions in current practice. METHODS: Patients with acute ischemic stroke due to isolated M2 occlusions who were enrolled in the prospective multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and March 2020 were included. The primary outcome was a favorable outcome, defined as modified Rankin Scale (mRS) score of 0-2 at 90 days. Successful reperfusion was defined as an improvement of ≥1 points in the modified Thrombolysis In Cerebral Infarction score between the first and the last intracranial angiogram. RESULTS: A total of 458 patients were included (median National Institutes of Health Stroke Scale (NIHSS) score 14; 61.4% received prior intravenous thrombolysis). Compared with the non-reperfused patients, reperfused patients had an increased rate of excellent outcome (OR 2.3, 95% CI 0.98 to 5.36; p=0.053), favorable outcome (OR 2.79, 95% CI 1.31 to 5.93; p=0.007), and reduced 90-day mortality (OR 0.39, 95% CI 0.19 to 0.79; p<0.01). Admission NIHSS score was the only predictor of successful reperfusion. First-line strategy was not a predictor of successful reperfusion or favorable outcome, but the use of a stent retriever, alone or with an aspiration catheter, was associated with higher rates of procedural complications and 90-day mortality. CONCLUSIONS: Successful reperfusion of M2 occlusions reduced disability and mortality. However, safety is a concern, especially if the procedure failed.

First-line thrombectomy strategy for anterior large vessel occlusions: results of the prospective ETIS egistry.

BACKGROUND: The best recanalization strategy for mechanical thrombectomy (MT) remains unknown as no randomized controlled trial has simultaneously evaluated first-line stent retriever (SR) versus contact aspiration (CA) versus the combined approach (SR+CA). OBJECTIVE: To compare the efficacy and safety profiles of SR, CA, and SR+CA in patients with acute ischemic stroke (AIS) treated by MT. METHODS: We analyzed data of the Endovascular Treatment in Ischemic Stroke (ETIS) Registry, a prospective, multicenter, observational study of patients with AIS treated by MT. Patients with M1 and intracranial internal carotid artery (ICA) occlusions between January 2015 and March 2020 in 15 comprehensive stroke centers were included. We assessed the association of first-line strategy with favorable outcomes at 3 months (modified Rankin Scale score 0-2), successful recanalization rates (modified Thrombolysis In Cerebral Infarction (mTICI) 2b/3), and safety outcomes. RESULTS: We included 2643 patients, 406 treated with SR, 1126 with CA, and 1111 with SR+CA. CA or SR+CA achieved more successful recanalization than SR for M1 occlusions (aOR=2.09, (95% CI 1.39 to 3.13) and aOR=1.69 (95% CI 1.12 to 2.53), respectively). For intracranial ICA, SR+CA achieved more recanalization than SR (aOR=2.52 (95% CI 1.32 to 4.81)), no differences were observed between CA and SR+CA. SR+CA was associated with lower odds of favorable outcomes compared with SR (aOR=0.63 (95% CI 0.44 to 0.90)) and CA (aOR=0.71 (95% CI 0.55 to 0.92)), higher odds of mortality at 3 months (aOR=1.56 (95% CI 1.22 to 2.0)) compared with CA, and higher odds of symptomatic intracranial hemorrhage (aOR=1.59 (95% CI 1.1 to 2.3)) compared with CA. CONCLUSIONS: Despite high recanalization rates, our results question the safety of the combined approach, which was associated with disability and mortality. Randomized controlled trials are needed to evaluate the efficacy and safety of these techniques.

Collateral status reperfusion and outcomes after endovascular therapy: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) Registry.

BACKGROUND: Studies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes. METHODS: We used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0-2) versus good (grade 3-4) collaterals. RESULTS: Among 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0-2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0-1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group. CONCLUSIONS: Collateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion.

Aphasia outcome: the interactions between initial severity, lesion size and location.

OBJECTIVES: The outcome of aphasia at 3 months is variable in patients with moderate/severe stroke. The aim was to predict 3-month aphasia outcome using prediction models including initial severity in addition to the interaction between lesion size and location at the acute phase. METHODS: Patients with post-stroke aphasia (assessed by the Aphasia Rapid Test at day 7-ART D7) and MRI performed at day 1 were enrolled (n = 73). Good outcome at 3-months was defined by an Aphasia Handicap Score of 0-2. Each infarct lesion was overlapped with an area of interest in the left temporo-parietal region to compute an intersection index (proportion of the critical region damaged by the infarct). We tested ART D7, age, lesion volume, and intersection index as well as a combined variable lesion volume*intersection in a univariate analysis. Then, we performed a multivariate analysis to investigate which variables were independent predictors of good outcome. RESULTS: ART at D7, infarct volume, and the intersection index were univariate predictors of good outcome. In the multivariate analysis, ART D7 and "volume ≥ 50 ml or intersection index ≥ 20%" correctly classified 89% of the patients (p < 0.0001). When added to the model, the interaction between both variables was significant indicating that the impact of the size or site variable depends on the initial severity of aphasia. CONCLUSION: In patients with initially severe aphasia, large infarct size or critical damage in left temporoparietal junction is associated with poor language outcome at 3 months.

Susceptibility vessel sign on MRI predicts better clinical outcome in patients with anterior circulation acute stroke treated with stent retriever as first-line strategy.

BACKGROUND: Susceptibility vessel sign (SVS) can be a useful MRI biomarker of an occlusion but its relationship with clinical outcomes of acute ischemic stroke (AIS) is yet to be fully elucidated. OBJECTIVE: To investigate SVS in relation to the clinical outcomes after mechanical thrombectomy using a stent retriever (SR) as first-line approach in patients with AIS. MATERIAL AND METHODS: We included patients with a first-line SR approach for anterior AIS from the the Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) and THRombectomie des Artères CErebrales (THRACE) trials when both baseline imaging of SVS and 90-day modified Rankin Scale (mRS) scores were available. Patients were assigned to two groups based on the presence of an SVS (independent core laboratory), and the overall distributions of the mRS score at 90 days (shift analysis) and clinical independence (mRS score ≤2) were compared. RESULTS: 217 patients were included and SVS was diagnosed in 76.0% of cases (n=165, 95% CI 70.4% to 81.7%). After adjustment for potential confounders, SVS+ was significantly associated with 90-day mRS improvement (adjusted common OR=2.75; 95% CI 1.44 to 5.26) and favorable outcome (adjusted common OR=2.76; 95% CI 1.18 to 6.45). CONCLUSION: Based on results for patients of the ASTER and THRACE trials receiving first-line SR treatment, SVS was associated with lower disability at 3 months. Large prospective studies using MRI-based thrombus evaluation are warranted.

Cerebrovascular events in Takayasu arteritis: a multicenter case-controlled study.

OBJECTIVES: Takayasu arteritis (TA) is a giant cell arteritis usually affecting young women and characterized by inflammatory and ischemic signs of large vessel involvement, including extracranial cerebral arteries. The impact of stroke on TA prognosis has not been well evaluated. METHODS: We performed a retrospective multicenter review of patients with definite TA who experienced at least one stroke and compared the findings to 17 matched patients with TA diagnosis without neurological involvement. RESULTS: Seventeen patients (15 women, median age at stroke diagnosis 44 years) receiving a diagnosis of TA and stroke between 2002 and 2016 in our institution were included, from a cohort of 126 patients suffering from TA (13.5%). At diagnosis, patients from both groups had comparable cardiovascular risk factors. The first cerebrovascular event was ischemic stroke (n = 15) or transient ischemic attack (n = 2). In eight patients, stroke occurred after the TA diagnosis was made. In four patients, stroke occurred after carotid surgery. At the end of follow-up, 59% of patients had a neurological impairment, 35% had a recurrence of stroke, and 24% suffered from epilepsy. CONCLUSIONS: Stroke is a major cause of disability in TA patients. Internal carotid surgery may be performed with caution because of the risk of stroke after the procedure.

Non-ischemic cerebral enhancing lesions secondary to endovascular aneurysm therapy: nickel allergy or foreign body reaction? Case series and review of the literature.

INTRODUCTION: Delayed onset of non-ischemic cerebral enhancing (NICE) lesions is a rare complication of intracranial aneurysms' endovascular therapy (EVT). The purpose of this study is to report this rare complication and its potential pathophysiology in a single-center case series and review the relevant literature. METHODS: After retrospective review of all patients managed by EVT at our institution from January 1, 2012 to December 31, 2014, 2 out of 374 patients (0.5 %) with such a complication were identified. Skin patch testing was performed with all endovascular devices used in the two patients and with the European baseline series, including nickel. All previously published cases in the English literature were reviewed based on exhaustive PubMed and Embase research. RESULTS: Patient no. 1 developed NICE lesions 1 month after balloon-assisted coiling of a ruptured anterior communicating artery aneurysm. Patient no. 2 developed NICE lesions 12 months (the longest delay reported to date for such a complication) after the treatment of a right carotid-ophthalmic aneurysm by loose coiling and flow diversion. Patient no. 2 demonstrated nickel skin reactivity, but none of the two patients presented allergic reaction to the devices used during interventions. CONCLUSIONS: Based on our observations and review of the literature, we hypothesize that delayed non-ischemic cerebral enhancing lesions after EVT are more likely related to foreign body emboli rather than nickel allergy. The two presented cases demonstrate the potential for recurrence and prolonged fluctuation of NICE lesions, warranting long-term follow-up for all patients presenting this complication.