Serge Bracard

Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial: results up to 4 years from a randomised, multicentre trial

BACKGROUND Carotid stenting is a potential alternative to carotid endarterectomy but whether this technique is as safe as surgery and whether the long-term protection against stroke is similar to that of surgery are unclear. We previously reported that in patients in the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the rate of any stroke or death within 30 days after the procedure was higher with stenting than with endarterectomy. We now report the results up to 4 years. METHODS In this follow-up study of a multicentre, randomised, open, assessor-blinded, non-inferiority trial, we compared outcome after stenting with outcome after endarterectomy in 527 patients who had carotid stenosis of at least 60% that had recently become symptomatic. The primary endpoint of the EVA-3S trial was the rate of any periprocedural stroke or death (ie, within 30 days after the procedure). The prespecified main secondary endpoint was a composite of any periprocedural stroke or death and any non-procedural ipsilateral stroke during up to 4 years of follow-up. Other trial outcomes were any stroke or periprocedural death, any stroke or death, and the above endpoints restricted to disabling or fatal strokes. This trial is registered with ClinicalTrials.gov, number NCT00190398. FINDINGS 262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4 years of follow-up was higher with stenting than with endarterectomy (11.1%vs 6.2%, hazard ratio [HR] 1.97, 95% CI 1.06-3.67; p=0.03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2.00 (0.75-5.33; p=0.17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1.77 (1.03-3.02; p=0.04). For any stroke or death, the HR was 1.39 (0.96-2.00; p=0.08). INTERPRETATION The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis.

Multivariate Analysis of Predictors of Cerebral Vasospasm Occurrence After Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well. METHODS Symptomatic vasospasm was defined as the association of deterioration in a patients neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay. RESULTS Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1. 77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae. CONCLUSIONS Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.

Risk of stroke and recurrent dissection after a cervical artery dissection: A multicenter study

Objective: To assess the risk of stroke, TIA, or dissection recurrence after a first event of cervical artery dissection (CAD). Methods: The authors undertook a historical cohort study of consecutive patients with a first event of CAD who were admitted in 24 departments of neurology within a period of at least 1 year. Patients were retrospectively selected from a stroke data bank or from the local administrative data bank using the 10th revision of the International Statistical Classification of Diseases. A neurologist and a radiologist reviewed all charts to validate diagnosis and collect data. In 2002, patients were interviewed by phone or during a visit by the local investigators. Results: Four hundred fifty-nine patients (mean age 44.0 ± 9.7 years) were included in the study. Among the 457 survivors, 25 (5.5%) could not be contacted in 2002 because they had moved. After a mean follow-up of 31 months, four (0.9%) patients presented a recurrent ischemic stroke attributable to either not yet completely recovered initial CAD (n = 2) or a recurrent CAD (n = 2). Eight (1.8%) patients had a TIA without CAD recurrence. Two TIA occurred at the acute stage of CAD. Of the six remaining TIA, only one was associated with chronic arterial stenosis. In addition, two patients had recurrent CAD without stroke, giving a total of four (0.9%) CAD recurrences. Conclusions: Patients with a first event of CAD have a very low risk of ischemic events or dissection recurrences. Ischemic events seem rarely to be in relation with chronic arterial lesions.

Prospective study of symptomatic atherothrombotic intracranial stenoses The GESICA Study

Background: Symptomatic intracranial atherothrombotic stenoses (ICAS) are associated with high rates of cerebrovascular ischemic events. Objective: To conduct a prospective multicenter study to evaluate the natural history of ICAS and, in those patients refractory to medical treatment, the outcomes associated with intracranial angioplasty. Methods: Patients aged 18 to 80 were enrolled with symptoms attributed to a single ICAS of ≥50%. Optimal medical therapy of vascular risk factors and preventive antithrombotic therapy were at the discretion of the local investigator. Patients were eligible for intracranial angioplasty after experiencing recurrent stroke despite medical therapy. Neurologic and ultrasonographic examinations were performed at study inclusion, 3 months after enrollment, and every 6 months of follow-up thereafter, for 36 months. Results: One hundred two patients were included, with a mean age of 63.3 ± 10.4 years. Intracranial artery stenoses involved the vertebral artery in 22.5%, the basilar artery in 25.5%, the middle cerebral artery in 26.5%, and the internal carotid artery in 25.5%. In 27.4% of the patients, the stenoses had clinical hemodynamic characteristics. During a mean follow-up of 23.4 months, 38.2% of the patients had a cerebrovascular event: ischemic stroke in 13.7% and TIA in 24.5%. Among patients with a hemodynamically significant stenosis, 60.7% had a recurrent stroke or TIA in the territory of the stenotic artery; this association was significant in univariate analysis. Twenty-eight patients underwent an endovascular procedure with a neurologic periprocedural complication rate of 14.2%. The overall vascular death rate was 8.8%. Conclusions: Despite medical treatment, the 2-year recurrence rate of ischemic events in the territory of the stenotic artery was 38.2%. Cardiovascular events occurred in 18.6% of patients. Clinically significant hemodynamic stenoses were associated with stroke recurrence and may help identify a high risk subset of patients.

Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial

BACKGROUND Intravenous thrombolysis with alteplase alone cannot reperfuse most large-artery strokes. We aimed to determine whether mechanical thrombectomy in addition to intravenous thrombolysis improves clinical outcome in patients with acute ischaemic stroke. METHODS THRACE is a randomised controlled trial done in 26 centres in France. Patients aged 18-80 years with acute ischaemic stroke and proximal cerebral artery occlusion were randomly assigned to receive either intravenous thrombolysis alone (IVT group) or intravenous thrombolysis plus mechanical thrombectomy (IVTMT group). Intravenous thrombolysis (alteplase 0·9 mg/kg [maximum 90 mg], with an initial bolus of 10% of the total dose followed by infusion of the remaining dose over 60 min) had to be started within 4 h and thrombectomy within 5 h of symptom onset. Occlusions had to be confirmed by CT or magnetic resonance angiography. Randomisation was done centrally with a computer-generated sequential minimisation method and was stratified by centre. The primary outcome was the proportion of patients achieving functional independence at 3 months, defined by a score of 0-2 on the modified Rankin scale, assessed in the modified intention-to-treat population (ie, patients lost to follow-up and those with missing data were excluded). Safety outcomes were analysed in the per-protocol population (ie, all patients who did not follow the protocol of their randomisation group precisely were excluded from the analysis). THRACE is registered with ClinicalTrials.gov, NCT01062698. FINDINGS Between June 1, 2010, and Feb 22, 2015, 414 patients were randomly assigned to the IVT group (n=208) or the IVTMT group (n=204). Four patients (two in each group) lost to follow-up and six (four in the IVT group and two in the IVTMT group) with missing data were excluded. 85 (42%) of 202 patients in the IVT group and 106 (53%) of 200 patients in the IVTMT group achieved functional independence at 3 months (odds ratio 1·55, 95% CI 1·05-2·30; p=0·028). The two groups had no significant differences in mortality at 3 months (24 [12%] deaths of 202 patients vs 27 [13%] of 206; p=0·70) or symptomatic intracranial haemorrhage at 24 h (four [2%] of 185 vs three [2%] of 192; p=0·71). Common adverse events related to thrombectomy were vasospasm (33 [23%] patients) and embolisation in a new territory (nine [6%]). INTERPRETATION Mechanical thrombectomy combined with standard intravenous thrombolysis improves functional independence in patients with acute cerebral ischaemia, with no evidence of increased mortality. Bridging therapy should be considered for patients with large-vessel occlusions of the anterior circulation. FUNDING French Ministry for Health.

Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints.

Background and Purpose— Arterial stiffening and thickening and endothelial dysfunction may be associated with cognitive decline or white matter hyperintensities (WMH) independently of blood pressure level. We aimed to investigate, using an integrative approach, the relative contributions of structural and functional vascular factors to the degree of cognitive impairment (primary outcome) and the severity of WMH (secondary outcome) in elderly hypertensive patients with subjective memory complaints, a group prone to dementia. Methods— A prospective, dedicated, cross-sectional population of 198 elderly hypertensive patients (mean age 69.3±6.2 years) with subjective memory complaints underwent a full set of cognitive function assessments, brain MRI with semiquantification of WMH, carotid ultrasonography, carotid–femoral pulse wave velocity, brachial endothelial function, and plasma von Willebrand Factor measurements. Results— After adjustment for the usual cardiovascular risk factors, increased arterial stiffness (as assessed by pulse wave velocity) was significantly and independently associated with memory impairment in men. The severity of WMH was independently associated with increased carotid intima media thickness and stiffness (as assessed by augmentation index) as well as with increased age and plasma levels of von Willebrand Factor, a biomarker of endothelial dysfunction. Conclusions— Our data suggest that vascular abnormalities, independently of blood pressure levels, may play a role in the setting of subjective memory complaints as well as of WMH in elderly hypertensive patients. Arterial thickness and stiffness as well as endothelial function should be assessed simultaneously and may represent additional targets for the prevention of subjective memory complaints and WMH.

Vasospasm after subarachnoid hemorrhage: interest in diffusion-weighted MR imaging.

Background and Purpose— Vasospasm secondary to subarachnoid hemorrhage (SAH) is responsible for severe ischemic complications. Although effective, angioplasty must be performed at a very early stage to produce any clinical recovery. Diagnostic investigations to assess arterial narrowing (transcranial Doppler, angiography) or cerebral perfusion (xenon CT, single-photon emission CT) do not provide evidence of the extent of parenchymal ischemia. In stroke, diffusion-weighted MR imaging (DWI) appears to be the most sensitive procedure to detect cerebral ischemia. We studied asymptomatic vasospasm in patients with aneurysmal SAH to assess whether DWI provides predictive markers of silent ischemic lesions and/or progression toward symptomatic ischemia. Methods— Seven asymptomatic vasospasm patients (average blood velocity rates >120 cm/s), 3 patients with symptomatic vasospasm, and 4 patients with SAH but without vasospasm were studied at regular intervals by DWI, and their apparent diffusion coefficients (ADCs) were calculated. Results— All patients with vasospasm including those without symptoms presented abnormalities on DWI with a reduction of the ADC prevalently in the white matter. No such abnormalities were observed in patients without vasospasm. The abnormalities on DWI resolved completely in 4 of the 7 patients, with no parenchymal lesion. Resolution was partial in 3 patients whose white matter still presented residual round, focal ischemic lesions. Conclusions— Being able to correlate abnormalities on DWI with parenchymal involvement in asymptomatic patients would be of considerable clinical significance. It is hoped that larger studies will be undertaken to determine whether the ADC has a reversibility threshold, because this would facilitate patient management.

Efficacy of external fractionated radiation therapy in the treatment of meningiomas: a 20-year experience.

BACKGROUND This is a retrospective analysis of a series of meningiomas treated by radiotherapy. MATERIALS AND METHODS From 1978 to 1997, 45 patients with intracranial meningiomas were referred for external fractionated radiotherapy at Centre Alexis Vautrin. All patients were given 50-70Gy to the tumor bed (median: 56Gy), 1.8-2Gy per fraction. RESULTS Evaluation was performed in June 1999 using the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1-166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years; overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5 and 8 years. One major radiation-induced complication occurred in this series (decline of cognitive function). According to the indication of radiotherapy, we divided the series into four groups: postoperative irradiation after a first subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (+/-salvage surgery, 14 patients), 73%; after further recurrence (+/-salvage surgery, 11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients but one died before 42 months. Age at the time of irradiation (> or =60 vs. <60 years) and radiotherapy dose (> or =60 vs. <60Gy) did not influence local control or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a worse outcome than benign lesions (WHO grade I, P<0.01). CONCLUSIONS These results compare favorably with previously published data. External fractionated radiotherapy is well tolerated and effective. There is still a debate about the place of radiotherapy in the treatment of meningiomas: after subtotal resection, should radiotherapy be given postoperatively or at the time of progression? Should radiotherapy replace surgery when the risk of postoperative sequellae is high? Prospective randomized trials would be required to address these issues.

Effect of Endovascular Contact Aspiration vs Stent Retriever on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER Randomized Clinical Trial

Importance The benefits of endovascular revascularization using the contact aspiration technique vs the stent retriever technique in patients with acute ischemic stroke remain uncertain because of lack of evidence from randomized trials. Objective To compare efficacy and adverse events using the contact aspiration technique vs the standard stent retriever technique as a first-line endovascular treatment for successful revascularization among patients with acute ischemic stroke and large vessel occlusion. Design, Setting, and Participants The Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) study was a randomized, open-label, blinded end-point clinical trial conducted in 8 comprehensive stroke centers in France (October 2015-October 2016). Patients who presented with acute ischemic stroke and a large vessel occlusion in the anterior circulation within 6 hours of symptom onset were included. Interventions Patients were randomly assigned to first-line contact aspiration (n = 192) or first-line stent retriever (n = 189) immediately prior to mechanical thrombectomy. Main Outcomes and Measures The primary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all endovascular procedures. Secondary outcomes included degree of disability assessed by overall distribution of the modified Rankin Scale (mRS) score at 90 days, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events. Results Among 381 patients randomized (mean age, 69.9 years; 174 women [45.7%]), 363 (95.3%) completed the trial. Median time from symptom onset to arterial puncture was 227 minutes (interquartile range, 180-280 minutes). For the primary outcome, the proportion of patients with successful revascularization was 85.4% (n = 164) in the contact aspiration group vs 83.1% (n = 157) in the stent retriever group (odds ratio, 1.20 [95% CI, 0.68-2.10]; P = .53; difference, 2.4% [95% CI, −5.4% to 9.7%]). For the clinical efficacy outcomes (change in NIHSS score at 24 hours, mRS score at 90 days) and adverse events, there were no significant differences between groups. Conclusions and Relevance Among patients with ischemic stroke in the anterior circulation undergoing thrombectomy, first-line thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful revascularization rate at the end of the procedure. Trial Registration clinicaltrials.gov Identifier: NCT02523261

Treatment of hemorrhagic intracranial dissections: Commentary

OBJECTIVETo analyze the treatment options in hemorrhagic intracranial dissections. METHODSThis study involved a retrospective review of 27 patients with 29 dissections treated during a 16-year period, mainly by endovascular treatment (EVT). RESULTSEVT was performed in the acute stage in 12 of the 29 dissections, and occlusion was performed using coils at the dissection site in six dissections and with proximal balloon occlusion in six dissections. Wrapping was performed in one case. In the remaining 16 dissections, which were not treated, mainly for anatomic reasons, three patients died, one from rebleeding. Angiographic follow-up performed in the 13 surviving patients demonstrated an initially misdiagnosed lesion in one and worsening lesions in five that led to delayed EVT in five and surgical clipping in one. One of these dissections, which was located on a dominant vertebral artery, was treated after subsequent rupture using a stent and coils to preserve the patency of the parent vessel. Four ischemic complications related to EVT resulted in a moderate disability in two patients. No rebleeding occurred after EVT, but one patient died because of a poor initial clinical status; the other patients improved. In the 10 patients treated conservatively, four died, three from a poor initial clinical status and one from rebleeding, and six patients had a good clinical outcome. Of the 27 patients, three had rebleeding and one died as a result of that rebleeding. Seventeen patients (63%) had a good recovery, six (22%) had a moderate disability, and four (15%) died. CONCLUSIONEVT provides effective protection against rebleeding. When possible, occlusion with coils at the dissection site is the current method of choice. Another option is parent artery occlusion with balloons, and the use of a stent may preserve vessel permeability in specific cases.