Safety and efficacy of the Silk flow diverter: Insight from the DIVERSION prospective cohort study.

BACKGROUND AND PURPOSE: Flow diverters are considered as an essential tool in the stent-based treatment of complex intracranial aneurysms. We report here a subgroup analysis of the nationwide prospective DIVERSION study to investigate the safety and efficacy of the Silk flow diverter at 12 months follow-up. METHODS: We performed a subgroup analysis of patients included in the DIVERSION, a national prospective cohort study including all flow diverters placement between 2012 and 2014 in France, and treated with the Silk. The primary outcome was the morbi-mortality at 12 months, including death, morbidity event and aneurysm retreatment within 12 months post-treatment. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran's scale by an independent imaging core laboratory during follow-up. RESULTS: A total of 102 procedures involving 101 patients (mean age±standard deviation, 54.3±13.5 years) harbouring 118 aneurysms (113/118 located in the anterior circulation; mean size 8.2±7.1mm) were included. During the 12-month follow-up, 34 (33.3%) procedures experienced at least one morbi-mortality event: 3 deaths, 27 morbidity events and 4 retreatments. Overall, 1/3 deaths and 10/27 morbidity events were related to the device and/or the procedure, leading to a specific survival rate and a specific free-morbidity survival rate at 12 months of 98.98% [95% confidence interval, 92.98%-99.86%] and 89.73% [95%CI, 81.71%-94.36%], respectively. The rate of permanent-related neurological deficit was 5.9% within 12 months. One year follow-up imaging showed satisfactory occlusion in 82.2% of cases. CONCLUSION: Flow diversion with the Silk device has a reasonable safety and effectiveness profile for the endovascular treatment of intracranial aneurysms.

Impact of Antiplatelet Therapy During Endovascular Therapy for Tandem Occlusions: A Collaborative Pooled Analysis.

Background and Purpose- Antiplatelet agents could be used in the setting of endovascular therapy for tandem occlusions to reduce the risk of de novo intracranial embolic migration, reocclusion of the extracranial internal carotid artery lesion, or in-stent thrombosis in case of carotid stent placement but have to be balanced with the intracerebral hemorrhagic transformation risk. In this study, we aim to investigate the impact of acute antiplatelet therapy administration on outcomes during endovascular therapy for anterior circulation tandem occlusions. Methods- This is a retrospective analysis of a collaborative pooled analysis of 11 prospective databases from the multicenter observational TITAN registry (Thrombectomy in Tandem Lesions). Patients were divided into groups based on the number of antiplatelet administered during endovascular therapy. The primary outcome was favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 90 days. Results- This study included a total of 369 patients; 145 (39.3%) did not receive any antiplatelet agent and 224 (60.7%) received at least 1 antiplatelet agent during the procedure. Rate of favorable outcome was nonsignificantly higher in patients treated with antiplatelet therapy (58.3%) compared with those treated without antiplatelet (46.0%; adjusted odds ratio, 1.38 [95% CI, 0.78-2.43]; P=0.26). Rate of 90-day mortality was significantly lower in patients treated with antiplatelet therapy (11.2% versus 18.7%; adjusted odds ratio, 0.47 [95% CI, 0.22-0.98]; P=0.042), without increasing the risk of any intracerebral hemorrhage. Successful reperfusion (modified Thrombolysis in Cerebral Ischemia score 2b-3) rate was significantly better in the antiplatelet therapy group (83.9% versus 71.0%; adjusted odds ratio, 1.89 [95% CI, 1.01-3.64]; P=0.045). Conclusions- Administration of antiplatelet therapy during endovascular therapy for anterior circulation tandem occlusions was safe and was associated with a lower 90-day mortality. Optimal antiplatelet therapy remains to be assessed, especially when emergent carotid artery stenting is performed. Further randomized controlled trials are needed.

Endovascular Treatment Decision Making in Patients with Low Baseline ASPECTS: Insights from UNMASK EVT, an International Multidisciplinary Study.

BACKGROUND: Current stroke treatment guidelines restrict level 1A recommendations for endovascular therapy to patients with baseline ASPECTS score > 5. However, a recent meta-analysis from the HERMES-group showed treatment benefit in patients with ASPECTS ≤ 5. We aimed to explore how physicians across different specialties and countries approach endovascular treatment decision-making in acute ischemic stroke patients with low baseline ASPECTS. METHODS: In a multidisciplinary survey, 607 stroke physicians were randomly assigned 10 out of a pool of 22 case-scenarios, 3 of which involved patients with low baseline ASPECTS (A:40-year old with ASPECTS 4, B:33-year old with ASPECTS 2 C:72-year old with ASPECTS 3), otherwise fulfilling all EVT-eligibility criteria. Participants were asked how they would treat the patient A) under their current local resources and B) under assumed ideal conditions, without any external (monetary, policy-related or infrastructural) restraints. Overall and scenario-specific decision rates were calculated. Clustered multivariable logistic regression analysis was used to determine the association of baseline ASPECTS with endovascular treatment-decision. RESULTS: Baseline ASPECTS score was significantly associated with current (OR:1.09, CI 1.05-1.13) and ideal endovascular treatment-decision (OR:1.12, CI 1.08-1.16). Overall current and ideal treatment decision-rates for the low ASPECTS scenarios were 57.1% and 57.6%. Current and ideal rates for the two younger patients were higher (scenario A:69.9/60.4%, scenario B:60.0/61.5%) compared to the 72-year old patient (41.3/40.2%). CONCLUSION: Most physicians decided to proceed with endovascular treatment despite low baseline ASPECTS, particularly in younger patients. This may have implications on the design and execution of low ASPECTS randomized trials.

Influence of Guidelines in Endovascular Therapy Decision Making in Acute Ischemic Stroke: Insights From UNMASK EVT.

Background and Purpose- The American Heart Association and the American Stroke Association guidelines for early management of patients with ischemic stroke offer guidance to physicians involved in acute stroke care and clarify endovascular treatment indications. The purpose of this study was to assess concordance of physicians' endovascular treatment decision-making with current American Heart Association and the American Stroke Association stroke treatment guidelines using a survey-approach and to explore how decision-making in the absence of guideline recommendations is approached. Methods- In an international cross-sectional survey (UNMASK-EVT), physicians were randomly assigned 10 of 22 case scenarios (8 constructed with level 1A and 11 with level 2B evidence for endovascular treatment and 3 scenarios without guideline coverage) and asked to declare their treatment approach (1) under their current local resources and (2) assuming there were no external constraints. The proportion of physicians offering endovascular therapy (EVT) was calculated. Subgroup analysis was performed for different specialties, geographic regions, with regard to physicians' age, endovascular, and general stroke treatment experience. Results- When facing level 1A evidence, participants decided in favor of EVT in 86.8% under current local resources and in 90.6% under assumed ideal conditions, that is, 9.4% decided against EVT even under assumed ideal conditions. In case scenarios with level 2B evidence, 66.3% decided to proceed with EVT under current local resources and 69.7% under assumed ideal conditions. Conclusions- There is potential for improving thinking around the decision to offer endovascular treatment, since physicians did not offer EVT even under assumed ideal conditions in 9.4% despite facing level 1A evidence. A majority of physicians would offer EVT even for level 2B evidence cases.

Emergent Carotid Stenting Plus Thrombectomy After Thrombolysis in Tandem Strokes: Analysis of the TITAN Registry.

Background and Purpose: Emergent carotid artery stenting plus mechanical thrombectomy is an effective treatment for acute ischemic stroke patients with tandem occlusion of the anterior circulation. However, there is limited data supporting the safety of this approach in patients treated with prior intravenous thrombolysis (IVT). We aimed to investigate the safety of emergent carotid artery stenting-mechanical thrombectomy approach in stroke patient population treated with prior IVT Methods: ­We assessed patients with acute ischemic stroke because of atherosclerotic tandem occlusion that were treated with emergent carotid artery stenting-mechanical thrombectomy approach from the multicenter observational Thrombectomy in Tandem Lesions registry. Patients were divided into 2 groups based on pretreatment IVT (IVT versus no-IVT). Intracerebral hemorrhages were classified according to the European Cooperative Acute Stroke Study II criteria. Results: Among 205 patients included in the present study, 125 (60%) received prior IVT. Time from symptoms onsetto-groin puncture was shorter (234±100 versus 256±234 minutes; P=0.002), and heparin use was less in the IVT group (14% versus 35%; P<0.001); otherwise, there was no difference in the baseline characteristics. There was no significant difference between the IVT and no-IVT groups in the rate of symptomatic intracerebral hemorrhage (5% versus 8%; P=0.544), parenchymal hematoma type 1 to 2 (15% versus 18%; P=0.647), successful reperfusion (modified Thrombolysis in Cerebral Ischemia 2b­3), or 90-day favorable outcome (modified Rankin Scale score of 0­2 at 90 days). The 90-day all-cause mortality rate was significantly lower in the IVT group (8% versus 20%; P=0.017). After adjusting for covariates, IVT was not associated with symptomatic intracerebral hemorrhage or 90-day mortality Conclusions: Emergent carotid artery stenting-mechanical thrombectomy approach was not associated with an increased risk of hemorrhagic complications in tandem occlusion patients who received IVT before the intervention.

Acute Stroke With Large Ischemic Core Treated by Thrombectomy.

Background and Purpose- Acute stroke patients with a large ischemic core may still benefit from mechanical thrombectomy (MT), but the predictors of clinical outcome are not well known after MT. We investigated the clinical and imaging factors associated with good outcome and mortality at 90 days in acute stroke patients with a large baseline ischemic core treated with MT. Methods- Data from the multicentric prospective ETIS (Endovascular Treatment in Ischemic Stroke) registry of consecutive acute ischemic stroke patients treated with MT from January 1, 2012, to August 31, 2016, were retrospectively analyzed. Baseline large ischemic core was defined as diffusion-weighted imaging (DWI)-Alberta Stroke Program Early CT Score of ≤5. The degree of disability was assessed by the modified Rankin Scale at 90 days. Outcomes included good outcome (modified Rankin Scale score of ≤2), and mortality (modified Rankin Scale score of 6). Results- Among 216 patients with DWI-Alberta Stroke Program Early CT Score of ≤5 (median DWI volume 77 mL, interquartile range 52-120 mL) treated with MT, good outcome was achieved in 55 (25.4%) patients and 75 (34.7%) died at 90 days. Hemorrhagic transformation was detected in 40 (18.5%) patients within 24 hours post-MT. Older age (adjusted odds ratio [OR] for every 10 years, 0.62; 95% CI, 0.48-0.80; P<0.001) and increased DWI lesional volume (adjusted OR, 0.98; 95% CI, 0.97-0.99; P<0.001) were associated with a lower chance of achieving a good outcome, while successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] grades of ≤2b) predicted good outcome (adjusted OR, 4.56; 95% CI, 1.79-11.62; P=0.001). Successful recanalization (OR, 0.46; 95% CI, 0.22-0.97; P=0.042), increased DWI lesional volume (OR, 1.02; 95% CI, 1.01-1.03; P<0.001), age (OR for every 10 years, 1.72; 95% CI, 1.31-2.26; P<0.001), and diabetes mellitus (OR, 3.23; 95% CI, 1.34-7.8; P=0.009) were independent predictors of 90-day mortality. Conclusions- Successful recanalization and baseline DWI lesional volume are the strongest predictors of outcome in stroke patients with a large ischemic core.

Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study.

Background and Purpose- Flow diverters are used for endovascular therapy of intracranial aneurysms. We did a nationwide prospective study to investigate the safety and effectiveness of flow diversion at 12 months. Methods- DIVERSION was a national prospective cohort study including all flow diverters placement between October 2012 and February 2014 in France. The primary end point was the event-free survival rate at 12 months, defined as the occurrence of morbidity (intracranial hemorrhage, ischemic stroke, noncerebral hemorrhage, or neurological deficit due to mass effect), retreatment, or death within 12 months post-treatment. A quality control was carried out on 100% of the collected data and of at least 10% of the included patients in each center, chosen at random. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran scale by an independent imaging core laboratory at 12 months. Results- We enrolled 398 patients harboring 477 intracranial aneurysms. At least 1 morbidity-mortality event was noted in 95 of 408 interventions representing an event-free survival rate of 75.7% (95% CI, 71.1-79.7). The rate of permanent-related serious events and mortality was 5.9% and 1.2% at 12 months, respectively. Multivariate analysis showed that high baseline blood pressure (hazard ratio, 2.54; 95% CI, 1.35-4.79; P=0.039), diabetes mellitus (hazard ratio, 3.70; 95% CI, 1.60-8.6; P=0.0022), and larger aneurysms (hazard ratio, 1.07; 95% CI, 1.04-1.11; P<0.0001) were associated with the occurrence of a neurological deficit. The satisfactory occlusion rate at 12 months was 79.9%, and the absence of high baseline blood pressure (odds ratio, 2.01; 95% CI, 1.12-3.71; P=0.0193) and postprocedural satisfactory occlusion (odds ratio, 2.75; 95% CI, 1.49-5.09; P=0.0012) were associated with a 12-month satisfactory occlusion. Conclusions- A satisfactory occlusion was achieved in almost 80% of cases after flow diverter treatment with a permanent-related serious event and mortality rates of 5.9% and 1.2% at 12 months, respectively.

Hemorrhagic Transformation After Thrombectomy for Tandem Occlusions.

Background and Purpose- Carotid artery stenting in tandem large vessel occlusion strokes is usually avoided because of the intracranial hemorrhagic risks induced by antiplatelet therapy during thrombectomy interventions. This study aimed to evaluate the incidence of hemorrhagic transformation following thrombectomy in large vessel occlusion strokes patients with atherosclerotic cervical carotid occlusion, associated factors, and clinical relevance. Methods- The TITAN (Thrombectomy in Tandem Lesions) collaboration pooled individual data of prospectively collected multicentric thrombectomy databases for consecutive anterior circulation tandem large vessel occlusion strokes patients who underwent thrombectomy. Hemorrhagic infarction (HI) and parenchymal hematoma (PH) were assessed within 24 hours. Results- Among 289 patients with atherosclerotic cause, 66 (24.7%) patients developed HI and 38 (14.2%) PH. Intracranial carotid occlusion, diabetes mellitus, absence of prior intravenous thrombolysis, and complete extracranial carotid occlusion were independent predictors of HI. Similar predictors were found for PH with addition of higher baseline National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score <7. No detrimental effect of HI on 90-day clinical outcome was found. The occurrence of PH was associated with increased mortality rates (adjusted odds ratio, 2.63; 95% CI, 1.05-6.59; P=0.039) and had no detrimental effect on 90-day modified Rankin Scale 0 to 2 (adjusted odds ratio, 0.52; 95% CI, 0.20-1.28; P=0.25). Conclusions- Incidence of PH after tandem large vessel occlusion strokes thrombectomy is equivalent to those reported in the literature data for isolated occlusions. Similar predictors were found for PH and HI within 24 hours, whereas acute carotid artery stenting and antiplatelet therapy were not, suggesting an aggressive endovascular treatment of tandem occlusions.

Factors Associated With the Decision-Making on Endovascular Thrombectomy for the Management of Acute Ischemic Stroke.

Background and Purpose- Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods- We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results- Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient's age (21.6%), and clinicians' experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions- In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients' age and physicians' experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.

Predictors for Mortality after Mechanical Thrombectomy of Acute Basilar Artery Occlusion.

BACKGROUND: Modern endovascular thrombectomy (MET), using stent retrievers or large-bore distal aspiration catheters in stroke patients with acute basilar artery occlusion (BAO), is routinely performed to date. However, more than 35% of BAO patients treated with MET die within 90 days despite high recanalization rates. The purpose of this study is to investigate the parameters associated with 90-day mortality in patients with BAO after MET. METHODS: We analyzed 117 consecutive BAO patients included in the Endovascular Treatment in Ischemic Stroke prospective clinical registry of consecutive acute ischemic stroke patients treated with MET (60 patients [51.3%] treated with a stent retriever as first-line technique) between March 2010 and April 2017. Successful recanalization was defined as modified thrombolysis In cerebral infarction scores 2b-3 at the end of MET, and mortality was defined as modified Rankin Scale 6 at 90 days. Associations of baseline characteristics (patient and treatment characteristics) and intermediate outcomes (recanalization, complications) with 90-day mortality were investigated in univariate and multivariate analyses. RESULTS: Overall successful recanalization rate was 79.5, and 41.9% (95% CI 32.8-51.0%) of patients died within 90 days after MET. Patients with successful recanalization had a lower mortality rate (32.9 vs. 74.4%; p < 0.001). Failure of successful recanalization was an independent predictor of mortality (OR 5.1; 95% CI 1.34-19.33). In multivariate analysis, age ≥60 years (OR 6.37; 95% CI 1.74-23.31), admission National Institute of Health Stroke Scale (NIHSS) ≥13 (OR 4.62; 95% CI 1.42-15.03), lower posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS; OR 1.71; 95% CI 1.19-2.44), use of antithrombotic medication prior to stroke onset (OR 3.38; 95% CI 1.03-11.08), absence of intravenous thrombolysis (OR 3.36; 95% CI 1.12-10.03), and angioplasty/stenting of the basilar artery (OR 4.71; 95% CI 1.34-16.54) were independent predictors for mortality after MET. CONCLUSIONS: Failure of successful recanalization was a strong predictor for mortality. In the setting of recanalization, age, admission NIHSS, pc-ASPECTS, absence of intravenous thrombolysis, and angioplasty/stenting of the basilar artery were also independent predictors for mortality after MET of BAO patients.

Cerebral Near-Infrared Spectroscopy: A Potential Approach for Thrombectomy Monitoring.

BACKGROUND AND PURPOSE: Regional brain oxygen saturation (rSO2) changes, assessed by cerebral near-infrared spectroscopy, are likely influenced by cerebral hemodynamic fluctuations induced by thrombectomy of acute proximal occlusion. We studied the correlations between rSO2 and baseline magnetic resonance imaging perfusion parameters and the relationship between rSO2 changes, recanalization, and clinical outcome. METHODS: Seventeen acute ischemic stroke patients, treated with mechanical thrombectomy, were monitored using bilateral near-infrared spectroscopy before, during, and continuously for 24 hours after the procedure. All patients had baseline brain magnetic resonance imaging with perfusion weighted imaging. RESULTS: rSO2 was only correlated with baseline Tmax (ρ=-0.42; P<0.05) and mean transit time (ρ=-0.45; P<0.05) within forehead explored areas. Before thrombectomy, an interhemispheric rSO2 difference was noted, and this diminished over time when recanalization had occurred (median [interquartile range], -8 [-12 to -5] to 3 [-3 to 7]; P=0.01). rSO2 changes were not correlated with clinical outcome. CONCLUSIONS: rSO2 was merely correlated with baseline Tmax and mean transit time magnetic resonance imaging perfusion parameters. Multiple sites recording beyond frontal pole explored areas may provide more relevant correlation with hemodynamic parameters.

Vascular Tissue-Type Plasminogen Activator Promotes Intracranial Aneurysm Formation.

BACKGROUND AND PURPOSE: Although the mechanisms that contribute to intracranial aneurysm (IA) formation and rupture are not totally elucidated, inflammation and matrix remodeling are incriminated. Because tPA (tissue-type plasminogen activator) controls both inflammatory and matrix remodeling processes, we hypothesized that tPA could be involved in the pathophysiology of IA. METHODS: Immunofluorescence analyses of tPA and its main substrate within the aneurysmal wall of murine and human samples were performed. We then compared the formation and rupture of IAs in wild-type, tPA-deficient and type 1 plasminogen activator inhibitor-deficient mice subjected to a model of elastase-induced IA. The specific contribution of vascular versus global tPA was investigated by performing hepatic hydrodynamic transfection of a cDNA encoding for tPA in tPA-deficient mice. The formation and rupture of IAs were monitored by magnetic resonance imaging tracking for 28 days. RESULTS: Immunofluorescence revealed increased expression of tPA within the aneurysmal wall. The number of aneurysms and their symptomatic ruptures were significantly lower in tPA-deficient than in wild-type mice. Conversely, they were higher in plasminogen activator inhibitor-deficient mice. The wild-type phenotype could be restored in tPA-deficient mice by selectively increasing circulating levels of tPA via hepatic hydrodynamic transfection of a cDNA encoding for tPA. CONCLUSIONS: Altogether, this preclinical study demonstrates that the tPA present in the blood stream is a key player of the formation of IAs. Thus, tPA should be considered as a possible new target for the prevention of IAs formation and rupture.

Thrombectomy in Acute Stroke With Tandem Occlusions From Dissection Versus Atherosclerotic Cause.

BACKGROUND AND PURPOSE: Tandem steno-occlusive lesions were poorly represented in randomized trials and represent a major challenge for endovascular thrombectomy in acute anterior circulation strokes. The impact of the cervical carotid lesion cause (ie, atherosclerotic versus dissection) on outcome of tandem patients endovascularly treated remains to be assessed. METHODS: We retrospectively analyzed individual data of prospectively collected consecutive tandem patients treated with endovascular thrombectomy. The primary outcome was favorable outcome at 90 days (modified Rankin Scale score of 0-2). Secondary efficacy outcomes included successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction scores of 2b-3), time to reperfusion, and safety outcomes encompassed procedural complications, symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Among the 295 included patients, 65 had cervical carotid dissection and 230 had cervical carotid atherosclerotic cause. The rate of favorable outcome was 56.3% in the dissection group versus 47.6% in the atherosclerotic arm (center-, age-, and admission National Institutes of Health Stroke Scale-adjusted odds ratio, 1.08; 95% confidence interval, 0.50-2.30; P=0.85). No significant differences were observed in secondary outcomes. The rates of successful reperfusion, symptomatic intracerebral hemorrhage, and 90-day mortality were 78.5% versus 74.5% (P=0.13), 4.6% versus 5.2% (P=1.0), and 7.8% versus 15.3% (P=0.94) in the dissection versus atherosclerotic groups, respectively. The median procedural time was 76 minutes (interquartile range, 52-95 minutes) in the dissection group and 67 minutes (interquartile range, 45-98 minutes) in the atherosclerotic group (P=0.24). CONCLUSIONS: We found no differences in the outcomes of patients with anterior circulation tandem atherosclerotic and dissection lesions treated with endovascular thrombectomy. Further studies are warranted.

Mechanical Thrombectomy for Minor and Mild Stroke Patients Harboring Large Vessel Occlusion in the Anterior Circulation: A Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Proximal large vessel occlusion (LVO) is present in up to 30% of minor strokes. The effectiveness of mechanical thrombectomy (MT) in the subgroup of minor stroke with LVO in the anterior circulation is still open to debate. Data about MT in this subgroup of patients are sparse, and their optimal management has not yet been defined. The purpose of this multicenter cohort study was to evaluate the effectiveness of MT in patients experiencing acute ischemic stroke (AIS) because of LVO in the anterior circulation, presenting with minor-to-mild stroke symptoms (National Institutes of Health Stroke Scale score of <8). METHODS: Multicenter cohort study involving 4 comprehensive stroke centers having 2 therapeutic approaches (urgent thrombectomy associated with best medical treatment [BMT] versus BMT first and MT if worsening occurs) about management of patients with minor and mild acute ischemic stroke harboring LVO in the anterior circulation. An intention-to-treat analysis was conducted. The primary end point was the rate of excellent outcome defined as the achievement of a modified Rankin Scale score of 0 to 1 at 3 months. RESULTS: Three hundred one patients were included, 170 with urgent MT associated with BMT, and 131 with BMT alone as first-line treatment. Patients treated with MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.0%) in the medical group had rescue MT because of neurological worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the 2 groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size. CONCLUSIONS: Minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT. There is thus an urgent need for randomized trials to define the effectiveness of MT in this patient subgroup.

Stent-Retriever Thrombectomy for Acute Anterior Ischemic Stroke with Tandem Occlusion: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety profile of stent-retriever thrombectomy (SRT) in acute anterior ischemic stroke patients with tandem occlusion. MATERIALS AND METHODS: Using the MEDLINE database, we conducted a systematic review and meta-analysis of all studies that included patients with acute ischemic stroke attributable to tandem occlusion who received treatment with SRT between November 2010 and May 2015. RESULTS: The literature search identified 11 previous studies involving a total of 237 subjects out of whom 193 (81.4 %) were treated with acute stent placement for the extracranial internal carotid artery occlusion. Mean initial NIHSS score was 17, and median time from onset to recanalization was 283.5 min. Mean intravenous thrombolysis rate was 63.8 %. In the meta-analysis, the recanalization rate reached 81 % (95 % CI, 73-89). Meta-analysis of clinical outcomes showed a pooled estimate of 44 % (95 % CI, 33-55; 10 studies) for favourable outcome, 13 % (95 % CI, 8-20; 10 studies) for mortality, and 7 % (95 % CI, 2-13; eight studies) for symptomatic intracranial haemorrhage. CONCLUSION: SRT with emergency carotid stenting is associated with acceptable safety and efficacy in acute anterior stroke patients with tandem occlusion compared to natural history. However, the best modality to treat proximal stenosis is based on an individual case basis. KEY POINTS: • Stent retriever thrombectomy of tandem occlusion is efficient and safe. • Emergent carotid stenting during thrombectomy increase symptomatic intracranial haemorrhage without impact mortality. • Thrombectomy of tandem anterior circulation occlusion may be the first therapeutic option.

Is Reperfusion Useful in Ischaemic Stroke Patients Presenting with a Low National Institutes of Health Stroke Scale and a Proximal Large Vessel Occlusion of the Anterior Circulation?

BACKGROUND: In population-based studies, patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients, and almost one-third of these patients are unable to ambulate independently at the time of discharge. Although mechanical thrombectomy (MT) has become the standard of care for acute ischaemic stroke with proximal large vessel occlusion (LVO) in the anterior circulation, the management of patients harbouring proximal occlusion and minor-to-mild stroke symptoms has not yet been determined by recent trials. The purpose of this study was to evaluate the impact of reperfusion on clinical outcome in low National Institutes of Health Stroke Scale (NIHSS) patients treated with MT. METHODS: We analysed 138 consecutive patients with acute LVO of the anterior circulation (middle cerebral artery M1 or M2 segment, internal carotid artery or tandem occlusion) with NIHSS <8, having undergone MT in 3 different centres. Reperfusion was graded using the modified thrombolysis in cerebral infarction (TICI) score and 3 grades were defined, ranging from failed or poor reperfusion (TICI 0, 1, 2A) to complete reperfusion (TICI 3). The primary clinical endpoint was an excellent outcome defined as a modified Rankin score (mRs) 0-1 at 3-months. The impact of reperfusion grade was assessed in univariate and multivariate analyses. The secondary endpoints included favourable functional outcome (90-day mRS 0-2), death and safety concerns. RESULTS: Successful reperfusion was achieved in 81.2% of patients (TICI 2B, n = 47; TICI 3, n = 65). Excellent outcome (mRs 0-1) was achieved in 69 patients (65.0%) and favourable outcome (mRs ≤2) in 108 (78.3%). Death occurred in 7 (5.1%). Excellent outcome increased with reperfusion grades, with a rate of 34.6% in patients with failed/poor reperfusion, 61.7% in patients with TICI 2B reperfusion, and 78.5% in patients with TICI 3 reperfusion (p < 0.001). In multivariate analysis adjusted for patient characteristics associated with excellent outcome, the reperfusion grade remained significantly associated with an increase in excellent outcome; the OR (95% CI) was 3.09 (1.06-9.03) for TICI 2B and 6.66 (2.27-19.48) for TICI 3, using the failed/poor reperfusion grade as reference. Similar results were found regarding favourable outcome (90-day mRs 0-2) or overall mRS distribution (shift analysis). CONCLUSION: Successful reperfusion is strongly associated with better functional outcome among patients with proximal LVO in the anterior circulation and minor-to-mild stroke symptoms. Randomized controlled studies are mandatory to assess the benefit of MT compared with optimal medical management in this subset of patients.

Outcomes of stent retriever thrombectomy in basilar artery occlusion: an observational study and systematic review.

BACKGROUND: Basilar artery occlusion (BAO) remains one of the most devastating subtypes of stroke with high mortality and poor outcome. Early recanalisation is the most powerful predictor of favourable outcome in patients with stroke, and may be improved with mechanical thrombectomy using stent retriever devices. However, the benefit in functional outcome and safety of stent retrievers are not yet well known. The aim of this study was to assess efficacy and safety profiles of stent retriever thrombectomy in BAO patients with stroke. METHODS: We analysed data retrospectively from our consecutive clinical series and conducted a systematic review and meta-analysis of all previous studies of stent retriever thrombectomy in BAO patients with stroke between November 2010 and April 2014. RESULTS: From March 2010 to March 2013, 22 patients with acute BAO were treated with a Solitaire stent retriever in our series. Favourable outcome was significantly associated with younger age and distal BAO. The literature search identified 15 previous studies involving a total of 312 subjects. In the meta-analysis, including our series data, the recanalisation rate (Thrombolysis In Cerebral Infarction (TICI) score ≥ 2b) reached 81% (95% CI 73% to 87%). The rate of symptomatic intracranial haemorrhage was 4% (95% CI 2% to 8%), favourable outcome (modified Rankin Scale (mRS) ≤ 2 at 3 months) was found in 42% (95% CI 36% to 48%) and mortality rate was 30% (95% CI 25% to 36%). CONCLUSIONS: Stent retriever thrombectomy is a safe treatment modality for patients with stroke presenting with BAO. Although the stent retrievers showed a good recanalisation rate, there are currently no randomised clinical trials to assess its clinical efficacy in comparison with the reference treatment.

Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

OBJECTIVES: To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. MATERIALS AND METHODS: A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. RESULTS: MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm2). Infarction volume (mean ± SD) was 90 ± 64 mm3 during ischemia and 57 ± 67 mm3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. CONCLUSION: This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. KEY POINTS: • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

Patient Outcomes with Stent-Retriever Thrombectomy for Anterior Circulation Stroke: A Meta-Analysis and Review of the Literature.

BACKGROUND: Mechanical thrombectomy with stent retrievers is now the reference therapy for acute ischemic stroke (AIS) in the anterior circulation in association with thrombolysis. We conducted an extensive systematic review and meta-analysis to evaluate the clinical and angiographic outcomes of stent-retriever thrombectomy in patients with acute anterior circulation stroke. Available literature published to date on observational studies and three randomized trials (MR CLEAN, ESCAPE, and EXTEND-IA) involving the stent-retriever device were reviewed. Successful recanalization and favorable clinical outcome were defined by a TICI ≥ 2b and modified Rankin Scale score of ≤ 2 at 90 days following AIS, respectively. A total of 2067 patients harboring an anterior circulation stroke were treated with a stent retriever: 433 patients from 3 randomized trials involving the device and 1634 patients from observational studies. Mean NIH Stroke Scale score on admission was 16.6, and mean time from onset to recanalization was 300 minutes. Successful recanalization was achieved in 82% (95%CI 77-86, 31 studies). The 90 day favorable outcome was achieved in 47% (95%CI 42-5.2, 34 studies) with an overall mortality rate of 17% (95%CI 13-20, 31 studies). Symptomatic intracerebral hemorrhage was identified in 6% (95%CI 4-8, 32 studies). In patients with AIS caused by a proximal intracranial occlusion of the anterior circulation, stent-retriever thrombectomy is safe and restores brain reperfusion in four of five treated patients, allowing favorable clinical outcome in one of two AIS patients with large vessel occlusion.

EVIDENCE trial: design of a phase 2, randomized, controlled, multicenter study comparing flow diversion and traditional endovascular strategy in unruptured saccular wide-necked intracranial aneurysms.

INTRODUCTION: Endovascular treatment of large, wide-necked intracranial aneurysms with coils is associated with low rates of initial angiographic occlusion and high rates of recurrence. The Pipeline™ Embolization Device has shown high rates of complete occlusion in uncontrolled clinical series. METHODS: The study is a prospective, controlled, randomized, multicenter, phase 2 open-label trial. Intention-to-treat population includes age ≥18, unruptured saccular aneurysm located in the intra-dural area, neck diameter ≥4 and ≤10 mm, sac diameter ≥7 mm and ≤20 mm, "dome/neck" ratio is ≥1, diameter of the parent artery ≥2 mm and ≤5 mm, and no prior treatment of the aneurysm. Site can only participate if five patients have been previously treated with the Pipeline device. The primary end point of the study is complete occlusion of the aneurysm on angiogram performed 12 months after the endovascular procedure. Complete aneurysm occlusion is defined as the absence of visible blood flow, grade 1 according to the Raymond scale for the standard procedure group and grade 4 according to the grading scale of Kamran for the flow diverter group. RESULTS: The trial is currently enrolling and results of the data are pending the completion of enrollment and follow-up. CONCLUSION: This paper details the trial design of the French EVIDENCE phase 2 trial, a blinded, controlled randomized trial of wide-neck intra-dural aneurysms amenable to either traditional endovascular strategy or flow diversion with Pipeline device.