General Anesthesia versus Sedation, Both with Hemodynamic Control, during Intraarterial Treatment for Stroke: The GASS Randomized Trial.

BACKGROUND: It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia. METHODS: In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7. RESULTS: Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95% CI, 0.69 to 1.19]; P = 0.474). Patients in the general anesthesia group experienced more intraoperative hypo- or hypertensive episodes, while the cumulative duration was not different (mean ± SD, 36 ± 31 vs. 39 ± 25 min; P = 0.079). The time from onset and from arrival to puncture were longer in the general anesthesia group (mean difference, 19 min [i.e., -00:19] [95% CI, -0:38 to 0] and mean difference, 9 min [95% CI, -0:18 to -0:01], respectively), while the time from onset to recanalization was similar in both groups. Recanalization was more often successful in the general anesthesia group (144 of 169 [85%] vs. 131 of 174 [75%]; P = 0.021). The incidence of symptomatic intracranial hemorrhage was similar in both groups. CONCLUSIONS: The functional outcomes 3 months after endovascular treatment for stroke were similar with general anesthesia and sedation. Our results, therefore, suggest that clinicians can use either approach.

GASS Trial study protocol: a multicentre, single-blind, randomised clinical trial comparing general anaesthesia and sedation during intra-arterial treatment for stroke.

INTRODUCTION: Treatment of acute stroke has drastically changed in the last 10 years. Endovascular therapy is now the standard of care for patients with a stroke caused by a large vessel occlusion in the anterior circulation. The impact of the type of anaesthesia (general anaesthesia or conscious sedation) during endovascular therapy on the outcome of the patients is still a matter of debate. Previous studies are mostly retrospective and/or focused on the early postprocedure outcome and/or without blood pressure goals and/or single-centre small size studies. We therefore designed a multicentre study hypothesising that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anaesthesia. METHODS/ANALYSIS: The General Anesthesia vs Sedation for Stroke (GASS) Trial is a randomised, parallel, single-blind, multicentre study of 350 patients undergoing endovascular therapy for the treatment of stroke. Patients will be randomly allocated to receive either a general anaesthesia or a conscious sedation. The primary outcome measure is the modified Rankin score assessed 3 months after the treatment. Data will be analysed on the intention-to-treat principle. ETHICS/DISSEMINATION: The GASS Trial has been approved by an independent ethics committee for all study centres. Participant recruitment begins in September 2016. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT02822144.

Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

Acute Neurologic Disorder from an Inhibitor of Fatty Acid Amide Hydrolase.

BACKGROUND: A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids. FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models, and some have been tested in phase 1 and 2 studies. In a phase 1 study, BIA 10-2474, an orally administered reversible FAAH inhibitor, was given to healthy volunteers to assess safety. METHODS: Single doses (0.25 to 100 mg) and repeated oral doses (2.5 to 20 mg for 10 days) of BIA 10-2474 had been administered to 84 healthy volunteers in sequential cohorts; no severe adverse events had been reported. Another cohort of participants was then assigned to placebo (2 participants) or 50 mg of BIA 10-2474 per day (6 participants). This report focuses on neurologic adverse events in participants in this final cohort. A total of 4 of the 6 participants who received active treatment consented to have their clinical and radiologic data included in this report. RESULTS: An acute and rapidly progressive neurologic syndrome developed in three of the four participants starting on the fifth day of drug administration. The main clinical features were headache, a cerebellar syndrome, memory impairment, and altered consciousness. Magnetic resonance imaging showed bilateral and symmetric cerebral lesions, including microhemorrhages and hyperintensities on fluid-attenuated inversion recovery and diffusion-weighted imaging sequences predominantly involving the pons and hippocampi. One patient became brain dead; the condition of two patients subsequently improved, but one patient had residual memory impairment, and the other patient had a residual cerebellar syndrome. One patient remained asymptomatic. CONCLUSIONS: An unanticipated severe neurologic disorder occurred after ingestion of BIA 10-2474 at the highest dose level used in a phase 1 trial. The underlying mechanism of this toxic cerebral syndrome remains unknown.

Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke.

OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. RESULTS: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34). CONCLUSIONS: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.

Influence of previous physical activity on the outcome of patients treated by thrombolytic therapy for stroke.

Physical activity prevents stroke and is associated with less severe strokes. The neuroprotective effect in patients treated with intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA), remains uncertain. We aimed at evaluating the relationship between previous physical activity and outcomes in stroke patients treated with i.v. rt-PA. OPHELIE-SPORT was a prospective observational multicenter study conducted in French and Japanese stroke patients treated with i.v. rt-PA. We evaluated the presence, weekly duration (<2, 2-5, >5 h) and intensity (light, moderate, heavy) of previous leisure-time physical activity according to standardized criteria. The primary end-point was an excellent outcome [modified Rankin Scale (mRS) 0-1 or similar to the pre-stroke mRS] after 3 months. Secondary end-points were good outcome (mRS 0-2 or similar to the pre-stroke mRS), and death. Of 519 patients, 74 (14.3 %) had regular physical activity before stroke. They were 14 years younger (p < 0.001), treated 25 min earlier (p = 0.004) and more likely to be men, free of pre-stroke handicap (mRS = 0), atrial fibrillation, arterial hypertension, and diabetes mellitus. National Institutes of Health Stroke Scale scores, at baseline (p = 0.183) and 24 h later (p = 0.203), did not differ between patients with and without physical activity. After adjustment on confounders, there was no association between previous leisure-time physical activity and outcome. Outcomes 3 months after treatment of cerebral ischaemia with i.v. rt-PA are not influenced by previous physical activity.

Supra-aortic arteries: three-dimensional time-resolved k-t BLAST contrast-enhanced MRA using a nondedicated body coil at 3 tesla in acute ischemic stroke.

PURPOSE: To assess the image quality and diagnostic performance achieved by using supra-aortic 3D-TR-CE-k-t BLAST MRA and a nondedicated body coil as compared with conventional CE-MRA in patients with acute ischemic stroke. MATERIALS AND METHODS: In this prospective study, 36 consecutive patients with a suspected acute ischemic stroke underwent both k-t BLAST MRA and conventional CE-MRA. Image quality was assessed using visual and quantitative criteria and the techniques were compared. Both techniques were compared for degree of visual and quantitative measurement of carotid stenosis. RESULTS: Delineation of vessel lumen and overall diagnostic confidence were significantly better with CE-MRA, respectively 3.4 ± 0.5 and 3.3 ± 0.6 (mean score ± SD), than with k-t BLAST MRA, respectively 2.8 ± 0.4 and 2.9 ± 0.5 (P < 0.02). SNR and CNR were significantly higher for k-t BLAST MRA, respectively 33.5 ± 19.3 and 27.9 ± 19.3, than for CE-MRA, respectively 25.7 ± 10 and 20.4 ± 8.4 (P < 0.03). Intertechnique agreement was good for carotid stenosis characterization (κ = .763). For the 14 relevant stenosis, stenosis measurements were highly correlated between techniques (0.96; P < 0.0001). The Bland-Altman plot showed a low bias in assessment of the degree of stenosis (mean bias 2.1% ± 7.7). CONCLUSION: k-t BLAST MRA using a nondedicated coil offering and dynamic information was a effective diagnostic tool for detection and characterization of carotid stenosis.

Improving detection of ischemic lesions at 3 Tesla with optimized diffusion-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: This study compared three different combinations of DWI parameters: three and six diffusion imaging directions (3dir and 6dir, respectively) using b=1000 or 2000 s/mm(2) (b1000 or b2000, respectively) to improve detection of recent ischemic lesions at 3 Tesla (3 T). MATERIALS AND METHODS: A total of 47 consecutive patients underwent three DWI scans: 3dir b1000; 6dir b1000; and 6dir b2000. Qualitative visual analysis was performed by three readers based on evaluation of the number of lesions, presence of artifacts and diagnostic confidence. Interobserver agreement, sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Forty-five lesions were detected by 3dir b1000, 52 by 6dir b1000 and 56 by 6dir b2000 in 30 patients. The additional lesions identified by 6dir b2000 were either small or located in the posterior fossa. Sensitivity with 6dir b2000 was significantly higher than with 3dir b1000 (98.1% vs 77.4%; P<0.05). CONCLUSION: At 3 T, 6dir b2000 DWI detected more acute ischemic lesions than 3dir b1000, particularly small lesions and those located in the brain stem.

Prognostic factors for outcomes after mechanical thrombectomy with solitaire stent.

BACKGROUND AND PURPOSE: Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke. This study was aimed at identifying factors influencing outcomes after thrombectomy with a Solitaire stent device. MATERIALS AND METHODS: Forty-five consecutive patients treated with thrombectomy using Solitaire FR were retrospectively included. Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months. RESULTS: Patient mean age and initial NIHSS score was 58 years (range 24-88) and 17 (range 6-32), respectively. An MRI was performed for 80% of patients, showing severe DWI lesion for 28% of patients and associated FLAIR hyperintensity for 58% of patients. Mean time from symptom onset to recanalization was 299min for the 32 ACO and 473min for the 13 PCO. Angiographic efficacy (TICI 2b-3) was achieved for 93% of patients and good clinical outcomes at discharge and at 3 months (mRS≤2) were achieved for 49% and 58% of patients, respectively. Independent prognostic factors for predicting good clinical outcomes at discharge were a short time to recanalization and FLAIR negativity. At 3 months, they were a short time to recanalization and patient age. DWI lesion severity was an associated prognostic factor. CONCLUSION: Two main prognostic factors for predicting a good clinical outcome after thrombectomy at 3 months were short time from symptom onset to recanalization and patient age.

Systematic combined noncontrast CT-CT angiography in the management of unexplained nontraumatic coma.

BACKGROUND: Nontraumatic impaired consciousness is a common issue in emergency departments with a serious but widely variable prognosis. STUDY OBJECTIVES: The aim of this prospective study was to evaluate the ability of systematic combined noncontrast computed tomography (NCCT)/computed tomography angiography (CTA) imaging, firstly to provide a neurologic prognosis and secondly to ensure early detection of basilar artery occlusion (BAO), in unexplained nontraumatic impaired consciousness management. METHODS: Combined NCCT/CTA imaging was performed on 65 patients with impaired consciousness and no history of trauma prospectively over 14 months in a single center. Images were assessed based on visual and quantitative criteria. Clinical outcome was assessed using the modified Rankin Scale at 3 months. Statistical analysis aimed to identify the prognostic value of combined NCCT/CTA imaging and its ability for early BAO detection. RESULTS: This study shows that combined NCCT/CTA imaging was a significant predictor of poor neurological outcome, with a positive predictive value of 94.6%. The combination was also crucial for early detection of BAO, given that 42.8% of cases were misdiagnosed with NCCT alone. Basilar artery occlusion represented 10.8% of all unexplained nontraumatic impaired consciousness. CONCLUSIONS: Systematic combined NCCT/CTA imaging is an efficient tool for predicting poor neurologic prognosis in cases of unexplained nontraumatic impaired consciousness and is also essential for detecting BAO.

An unfavorable dietary pattern is associated with symptomatic ischemic stroke and carotid atherosclerosis.

OBJECTIVE: Ischemic strokes represent more than 80% of total strokes in Western countries. The influence of dietary factors on ischemic stroke risk is debated mainly because available data are limited. Our objective was to compare the dietary pattern of symptomatic ischemic stroke patients under 65 years old with control subjects using a validated 14-item food frequency questionnaire (FFQ). We also compared symptomatic ischemic stroke patients with carotid atherosclerosis with those without according to the presence or the absence of carotid plaque defined by duplex scanning. METHODS: This was a case-control multi-center study that took place in one University hospital and two general hospitals in France. One hundred twenty-four symptomatic ischemic stroke patients (confirmation by a neurologist and imaging; 66% smokers) and 50 controls (34% smokers) without any known cardiovascular disease or previous nutritional advice were included. The main outcome measure(s) were intake scores for saturated (SFA), monounsaturated (MUFA), Omega-3 polyunsaturated (Omega-3 PUFA), and Omega-6 polyunsaturated fatty acids (Omega-6PUFA). Fruit and vegetables and an overall cardiovascular dietary score were evaluated with the FFQ. The overall cardiovascular score is calculated as (MUFA + Omega-3 PUFA + fruits and vegetables) - (SFA) scores. RESULTS: Compared with controls, ischemic stroke patients had a higher SFA score (6.6 +/- 3.0 vs 4.9 +/- 2.7; P < .001), lower scores of MUFA (0.8 +/- 0.9 vs 1.5 +/- 1.2; P < .001), Omega-3 PUFA (1.7 +/- 1.6 vs 2.2 +/- 1.5; P = .013), Omega-6PUFA (2.6 +/- 2.5 vs 3.9 +/- 2.7; P = .002), fruit and vegetables (2.9 +/- 1.7 vs 3.8 +/- 1.6; P = .005), and a lower overall dietary score (-1.2 +/- 5.0 vs 2.5 +/- 4.4; P < .001). These results remained statistically significant after adjustment for age, gender, and smoking status. Ischemic stroke patients with carotid atherosclerosis (n = 54) had a worse overall cardiovascular dietary score than those without (n = 68): -2.2 +/- 4.4 vs -0.2 +/- 5.2; P = .024. CONCLUSION: Compared with controls, ischemic stroke patients, especially those with carotid atherosclerosis, have an unfavorable dietary pattern (high SFA, low fruit and vegetables, and Omega-3 PUFA consumptions) that may have been a facilitating condition of the ischemic stroke. Dietary recommendations of a healthy diet should be useful in ischemic stroke prevention, especially in patients with cardiovascular risk factors.