Clinical and angiographic characteristics of ruptured and unruptured distal cerebral aneurysms: a review of a large series of cases in a high-volume center.

OBJECTIVE: To evaluate clinical, angiographic features, and endovascular approach of ruptured and unruptured distal intracranial aneurysms (DIAs). METHODS: From January 2013 to February 2022, details of all consecutive intracranial aneurysms (IAs) treated endovascularly in our center were collected and retrospectively reviewed. IAs involving the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery (distal to anterior communicating artery, limen insula, and P1 segment, respectively), and those distal to superior cerebellar artery, anterior-inferior cerebellar artery, and posterior inferior cerebellar artery's first segment were classified based on their etiology, location, size, and shape. Demographic, clinical, angiographic, and procedural variables, as well as follow-up outcomes were evaluated. RESULTS: Of 2542 IAs, 151 (5.9%) DIAs were counted (average size 5.4±2.9 mm), including 61 (40.4%) unruptured and 90 (59.6%) ruptured. No difference in the aneurysmal size was observed, but aneurysms smaller than 4 mm were observed more frequently in the ruptured group (36.7% vs 18%; P=0.01). In addition, ruptured DIAs were more often non-saccular (40% vs 18%; P=0.004) and irregular (93.3% vs 59%; P<0.001), They were treated mostly by coiling, glue, and parent artery sacrifice (P=0.02, P=0.006, and P=0.001), whereas unruptured DIAs were treated by stent-assisted coiling and flow-diverter stents (P=0.001 and P<0.001, respectively), without any differences in occlusion (81.6% vs 82.5%) and recanalization (21.1% vs 17.5%) rates. Procedure-related complications occurred in 20/151 (13.2%) patients, without any differences between subgroups. Ruptured DIAs were more often re-treated (18.4% vs 5.3%, P=0.02). In multivariate analyses, irregular shape appeared as an independent predictor of ruptured presentation (OR=8.1, 95% CI 3.0 to 21.7; P<0.001). CONCLUSIONS: Compared with unruptured DIAs, ruptured DIAs were more often non-saccular, irregular, and smaller than 4 mm. Despite different therapeutical approaches, ruptured and unruptured DIAs presented comparable occlusion and recanalization rates.

Effect of Bridging Thrombolysis on the Efficacy of Stent Retriever Thrombectomy Techniques : Insights from the SWIFT-DIRECT trial.

BACKGROUND: There are little available data regarding the influence of intravenous thrombolysis (IVT) on the efficacy of different first line endovascular treatment (EVT) techniques. METHODS: We used the dataset of the SWIFT-DIRECT trial which randomized 408 patients to IVT + EVT or EVT alone at 48 international sites. The protocol required the use of a stent retriever (SR), but concomitant use of a balloon guide catheter (BGC) and/or distal aspiration (DA) catheter was left to the discretion of the operators. Four first line techniques were applied in the study population: SR, SR + BGC, SR + DA, SR + DA + BGC. To assess whether the effect of allocation to IVT + EVT versus EVT alone was modified by the first line technique, interaction models were fitted for predefined outcomes. The primary outcome was first pass mTICI 2c­3 reperfusion (FPR). RESULTS: This study included 385 patients of whom 172 were treated with SR + DA, 121 with SR + DA + BGC, 57 with SR + BGC and 35 with SR. There was no evidence that the effect of IVT + EVT versus EVT alone would be modified by the choice of first line technique; however, allocation to IVT + EVT increased the odds of FPR by a factor of 1.68 (95% confidence interval, CI 1.11-2.54). CONCLUSION: This post hoc analysis does not suggest treatment effect heterogeneity of IVT + EVT vs EVT alone in different stent retriever techniques but provides evidence for increased FPR if bridging IVT is administered before stent retriever thrombectomy.

Ultra-Early "Fishmouth stenosis" and thrombosis of a Surpass Evolve flow diversion device following treatment of multiples right siphon aneurysms.

We present a case of ultra-early symptomatic fish-mouth type stenosis (FMTS) of a Surpass Evolve flow diverter stent (SE-FDS) occurring within 24 h after deployment for the treatment of multiple unruptured right siphon aneurysms in a 44-year-old patient. The patient developed left hemiplegia and hemineglect, and was treated with mechanical thrombectomy (MT) and Tirofiban infusion. This is the first report of an ultra-early FMTS with a SE-FDS and its mechanism is discussed in the light of available data in the literature.

Assessment of three MR perfusion software packages in predicting final infarct volume after mechanical thrombectomy.

AIMS: To evaluate the performance of three MR perfusion software packages (A: RAPID; B: OleaSphere; and C: Philips) in predicting final infarct volume (FIV). METHODS: This cohort study included patients treated with mechanical thrombectomy following an admission MRI and undergoing a follow-up MRI. Admission MRIs were post-processed by three packages to quantify ischemic core and perfusion deficit volume (PDV). Automatic package outputs (uncorrected volumes) were collected and corrected by an expert. Successful revascularization was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2B. Uncorrected and corrected volumes were compared between each package and with FIV according to mTICI score. RESULTS: Ninety-four patients were included, of whom 67 (71.28%) had a mTICI score ≥2B. In patients with successful revascularization, ischemic core volumes did not differ significantly from FIV regardless of the package used for uncorrected and corrected volumes (p>0.15). Conversely, assessment of PDV showed significant differences for uncorrected volumes. In patients with unsuccessful revascularization, the uncorrected PDV of packages A (median absolute difference -40.9 mL) and B (median absolute difference -67.0 mL) overestimated FIV to a lesser degree than package C (median absolute difference -118.7 mL; p=0.03 and p=0.12, respectively). After correction, PDV did not differ significantly from FIV for all three packages (p≥0.99). CONCLUSIONS: Automated MRI perfusion software packages estimate FIV with high variability in measurement despite using the same dataset. This highlights the need for routine expert evaluation and correction of automated package output data for appropriate patient management.

Cervicobrachial neuralgia due to vertebral artery loop.

PURPOSE: The main anatomic variations should be taught along with the classical anatomy curriculum, since they can mislead both diagnosis and treatment. We report here a clinical and radiological case of left C6 cervicobrachial neuralgia recurrence due to a vertebral artery loop, we then describe 13 published cases of such neurovascular conflicts. CASE: A 51-year-old woman suffered from recurrence of C6 cervicobrachial neuralgia after an initial C5-C6 decompression-fusion. Additional cervical angio-MR and CT scans found a tortuous aspect of the left vertebral artery that came into conflict with the left C6 spinal root, just after its emergence of the C5-C6 intervertebral foramen. A large posterior decompression was performed including a C5 and C6 left lateral mass resection to enlarge the foraminal space. The vertebral artery was kept in place. The patient reported a slow but consistent decrease in pain that disappeared after 3 months. Thirteen cases of a compressive vertebral loop are thereafter detailed. CONCLUSIONS AND DISCUSSION: Vascular precursors disarrangements can lead to a vertebral artery loop in contact with emerging cervical roots and potential clinical impact. This differential diagnosis should be considered for cervico-brachial neuralgia management. Moreover, the present case highlights the key role of a careful preoperative imaging assessment, as well as the need for robust knowledge of anatomy.

Surface-modified flow diverter p48-MW-HPC: Preliminary clinical experience in 28 patients treated in two centers.

BACKGROUND AND PURPOSE: Flow diversion is increasingly used for endovascular treatment of distal intracranial aneurysms and has led to the development of small diameter flow diverters such as p48-MW (phenox, Bochum, Germany). Use of flow diverters is limited, however, as patients require dual antiplatelet treatment to avoid thromboembolic complications. Hydrophilic Polymer Coating was developed to reduce platelet aggregation on the p48-MW (p48-MW-HPC). This study reports preliminary experience with p48-MW-HPC in aneurysm treatment in two centers. MATERIALS AND METHODS: Patients with ruptured, unruptured, and recanalized aneurysms treated with p48-MW-HPC were prospectively included and retrospectively analyzed for safety and efficacy. Safety was evaluated by analyzing intra- and postoperative complications as well as thromboembolic events depicted by DWI in the 72 h post-procedure. Efficacy was evaluated at 6 months based on aneurysm occlusion. RESULTS: From April 2019 to May 2020, 28 patients aged 25-82 years with 29 aneurysms were treated. Two thromboembolic events (7.1%) were reported with good clinical outcome. Final morbidity and mortality were both 0.0%. Post-operative DWI-MRI was depicting lesions in 70.0% of patients. Short-term (6 months) anatomical results were complete aneurysm occlusion in 87.0% of aneurysms, neck remnant in 8.7%, and aneurysm remnant in 4.3%. CONCLUSION: This preliminary clinical evaluation conducted in a relatively small sample size shows high feasibility (100.0%) of p48-MW-HPC aneurysm treatment, without morbidity or mortality, and high efficacy (complete occlusion in 90.0%). Additional larger comparative studies are needed to confirm these results and optimize perioperative antiplatelet treatment.

Effect of the COVID-19 pandemic on acute stroke reperfusion therapy: data from the Lyon Stroke Center Network.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period. METHODS: We conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods. RESULTS: A total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period [55 (54.5%) vs 74 (69.2%); p = 0.03]. The volume of MT remains stable over the two periods [72 (71.3%) vs 65 (60.8%); p = 0.14], but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260]; p < 0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410]; p < 0.01). CONCLUSIONS: Our study showed a decrease in the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.

DNMT1 mutations leading to neurodegeneration paradoxically reflect on mitochondrial metabolism.

ADCA-DN and HSN-IE are rare neurodegenerative syndromes caused by dominant mutations in the replication foci targeting sequence (RFTS) of the DNA methyltransferase 1 (DNMT1) gene. Both phenotypes resemble mitochondrial disorders, and mitochondrial dysfunction was first observed in ADCA-DN. To explore mitochondrial involvement, we studied the effects of DNMT1 mutations in fibroblasts from four ADCA-DN and two HSN-IE patients. We documented impaired activity of purified DNMT1 mutant proteins, which in fibroblasts results in increased DNMT1 amount. We demonstrated that DNMT1 is not localized within mitochondria, but it is associated with the mitochondrial outer membrane. Concordantly, mitochondrial DNA failed to show meaningful CpG methylation. Strikingly, we found activated mitobiogenesis and OXPHOS with significant increase of H2O2, sharply contrasting with a reduced ATP content. Metabolomics profiling of mutant cells highlighted purine, arginine/urea cycle and glutamate metabolisms as the most consistently altered pathways, similar to primary mitochondrial diseases. The most severe mutations showed activation of energy shortage AMPK-dependent sensing, leading to mTORC1 inhibition. We propose that DNMT1 RFTS mutations deregulate metabolism lowering ATP levels, as a result of increased purine catabolism and urea cycle pathways. This is associated with a paradoxical mitochondrial hyper-function and increased oxidative stress, possibly resulting in neurodegeneration in non-dividing cells.

Development and Validation of an UHPLC-MS/MS Assay for the Therapeutic Monitoring of Brivaracetam Plasma Concentrations in Patients with Epilepsy.

BACKGROUND: Brivaracetam is an antiepileptic drug used as an add-on therapy for partial-onset seizures in subjects aged 4 years and older. Owing to potential drug interactions and intersubject variability in plasma concentrations, therapeutic monitoring for brivaracetam may be useful. The aim of this study was to develop a simplified method for measuring brivaracetam plasma concentrations applicable to therapeutic drug monitoring in epilepsy. METHODS: An ultra high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated according to current guidelines for bioanalytical methods. Sample preparation (100 µL) involved only a simple precipitation step by acetonitrile. Brivaracetam-d7 was used as internal standard. The chromatographic analysis was performed by a Synergi Fusion column using 0.1% formic acid in water/acetonitrile as a binary gradient mobile phase, at a flow rate of 0.3 mL/min. Both brivaracetam and the internal standard eluted at 1.01 minutes. This method was applied to measure trough and 1-hour postmorning dose brivaracetam plasma concentrations of 11 patients with epilepsy. RESULTS: The method was validated over a concentration range of 0.10-10 mcg/mL. The mean recovery was 95%. Both intra- and inter-assay imprecision and inaccuracy were <15% for all quality control samples. The lower limit of quantitation and detection was 0.10 and 0.05 mcg/mL, respectively. No interferences or carry-over was observed. Median (25%-75% quartiles) trough and 1-hour postdosing brivaracetam plasma concentrations were 0.61 mcg/mL (0.47-0.83 mcg/mL) and 1.55 mcg/mL (1.24-2.12 mcg/mL), respectively, at a median dose of 80 mg/d (50-150 mg/d). Large, up to 8-fold, intrasubject fluctuations of brivaracetam concentrations between trough and 1-hour postdosing were observed. CONCLUSIONS: The present assay is faster and simpler than previously published analytical reports for brivaracetam in human plasma and is suitable for therapeutic drug monitoring.

Development and validation of volumetric absorptive microsampling coupled with UHPLC-MS/MS for the analysis of gamma-hydroxybutyric acid in human blood.

A volumetric microsampling (VAMS) device (20 µl) was evaluated and validated for the analysis of γ-hydroxybutyric acid (GHB) in venous blood using a simple ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. GHB was extracted from VAMS device by acetonitrile, after a re-hydration step in a temperature-controlled ultrasonic bath at 60°C for 10 min. Chromatographic analysis was carried out on a Kinetex C18 column using 0.1% formic acid in water and acetonitrile as binary gradient mobile phase (from 5 to 95% of acetonitrile from 1 to 2.5 min) at a flow rate of 0.3 ml/min. The VAMS method was fully validated according to current guidelines with satisfactory results in terms of linearity, selectivity, precision, absolute recovery, matrix effect and stability. The linearity was determined from 0.5 to 200 µg/ml and the lower limit of quantitation was 0.5 µg/ml. The novel VAMS-UHPLC-MS/MS method was successfully compared with plasma-based method in a GHB-treated patient as a proof of concept.

Cerebrospinal Fluid Concentrations of Nimodipine Correlate With Long-term Outcome in Aneurysmal Subarachnoid Hemorrhage: Pilot Study.

OBJECTIVES: The aim was to evaluate plasma and cerebrospinal fluid (CSF) nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage and their correlation with clinical outcome. METHODS: Nimodipine infusion was started at 1 mg/h and increased up to 2 mg/h and continued up to 21 days in surviving patients. Arterial and CSF samples were collected at least after 24 hours of stable nimodipine dosing. Delayed cerebral ischemia and vasospasm were documented by new neurological deficits and neuroimaging. The clinical outcome was assessed at 9 months by the modified Rankin scale. RESULTS: Twenty-three patients were enrolled. Nimodipine dose was 13 to 38 µg/kg per hour. Nimodipine arterial and CSF concentrations were 24.9 to 71.8 ng/mL and 37 to 530 pg/mL, respectively. Dose did not correlate with arterial or CSF concentrations. Arterial concentrations did not correlate with corresponding CSF concentrations. Doses and arterial concentrations did not correlate with the clinical outcome and were not associated with the occurrence of delayed cerebral ischemia. However, patients with no significant disability after 9 months of hemorrhage showed significantly higher CSF nimodipine concentrations (P = 0.015) and CSF-to-plasma ratios (P = 0.011) compared with patients who showed some degree of disability or who died. CONCLUSIONS: Cerebrospinal fluid nimodipine concentrations measured during hospital drug infusion showed a correlation with long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. These very preliminary data suggest that CSF concentrations monitoring may have some value in managing these patients.

Clinical pharmacokinetics of pramipexole, ropinirole and rotigotine in patients with Parkinson's disease.

INTRODUCTION: Pramipexole (PRA), ropinirole (ROP) and rotigotine (ROT) are non-ergoline dopaminergic agonists (DAs) used to treat Parkinson's disease (PD). Clinical pharmacokinetics of DAs is poorly characterized in PD. The main purpose of our study was to investigate the effect of dose, age and sex on steady-state plasma concentrations of DAs in real life PD patients on chronic DAs therapy. METHODS: The study was single center, open and prospective. Blood samples for measurement of DAs plasma concentrations were drawn in the morning, at a median 18-h distance from the last DA dose. RESULTS: Ninety-one patients treated with PRA, 50 with ROP and 37 with ROT were enrolled in the study. Plasma concentration of DAs significantly correlated with weight-adjusted daily dose in all subgroups, although at a given dose, matched plasma concentrations highly varied among patients. Median PRA plasma concentration-to-daily dose ratio (C/D) [(ng/mL)/(mg/kg/d)] was 68% higher in patients >65 years than ≤65 years (158 vs 94, p < 0.001), while was not affected by age in ROP and ROT subgroups. No sex-mediated differences in C/D ratios were observed in any group. CONCLUSION: These are the first observations on DAs pharmacokinetics in PD patients' everyday clinical practice. Of relevance, patients over 65yrs may require about one third of PRA dose compared to under 65yrs to achieve the same plasma concentration. Due to the high intersubject variability in plasma concentrations at the same dosage, we speculate that monitoring of plasma DAs might be helpful in the individualization of treatment in selected patients.

Impact of the Thrombectomy Trials on the Management and Outcome of Large Vessel Stroke: Data From the Lyon Stroke Center.

Introduction: Randomized trials (RT) have recently validated the superiority of thrombectomy over standard medical care, including intravenous thrombolysis (IVT). However, data on their impact on routine clinical care remains scarce. Methods: Using a prospective observational registry, we assessed: (1) the clinical and radiological characteristics of all consecutive patients treated with thrombectomy; (2) the outcome of all patients with M1 occlusion (treated with thrombectomy or IVT alone). Two periods were compared: before (2013-2014) and after (2015-2016) the publication of RT. Results: Endovascular procedures significantly increased between the two periods (N = 82 vs. 314, p < 0.0001). In 2015-2016, patients were older (median [IQR]: 69 [57-80]; vs. 66 [53-74]; p = 0.008), had shorter door-to-clot times (69 [47-95]; vs. 110 [83-155]; p < 0.0001) resulting in a trend toward shorter delay from symptom onset to reperfusion (232 [185-300]; vs. 250 [200-339]; p = 0.1), with higher rates of reperfusion (71 vs. 48%; p = 0.0001). Conversely, no significant differences in baseline NIHSS scores, ASPECTS, delay to IVT or intracranial hemorrhage were found. In 2015-2016, patients with M1 occlusion were treated with thrombectomy more often than in 2013-2014 (87 vs. 32%, respectively; p < 0.0001), with a significant improvement in clinical outcome (shift analysis, lower modified Rankin scale scores: OR = 1.68; 95% CI: 1.10-2.57; p = 0.017). Conclusion: Following the publication of RT, thrombectomy was rapidly implemented with significant improvements in intrahospital delay and reperfusion rates. Treatment with thrombectomy increased with better clinical outcomes in patients with M1 occlusion.

Tetrahydrocannabinol/Cannabidiol Oromucosal Spray in Patients With Multiple Sclerosis: A Pilot Study on the Plasma Concentration-Effect Relationship.

OBJECTIVES: We aimed to assess the potential relationship between intrasubject 9-tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray plasma profiles and clinical effects elicited by subacute dosing in chronically treated patients with multiple sclerosis (MS). METHODS: The study design was pilot, single center, open, and prospective. The patients were challenged with a morning test dose of 2 THC/CBD sprays at a 15-minute interval. Venous blood samples were collected before the first spray administration and every 30 minutes after the second spray, until 240 minutes postdosing. Patients rated their spasticity by the Numerical Rating Scale (NRS) simultaneously with blood drawings. Postural and motor tests were performed before the first spray and 90 and 180 minutes thereafter. RESULTS: Twelve patients were recruited. Peak plasma concentrations of THC/CBD largely varied among patients, from 0.60 to 13.29 ng/mL for THC and 0.55 to 11.93 ng/mL for CBD. Time to peak plasma concentrations ranged from 150 to 240 minutes for THC and 90 to 240 minutes for CBD. Patients' NRS serial scores decreased after dosing, from a median value of 6 to 3.5 (P < 0.001). A significant inverse correlation was observed between median intrasubject repeated NRS scores and corresponding median values of both THC (P < 0.01) and CBD (P < 0.002) plasma concentrations. No significant effect of cannabinoids dosing could be appreciated according to posturographic and motor tests. CONCLUSIONS: Our kinetic dynamic findings from THC/CBD oromucosal spray are the first obtained in real MS patients. Although preliminary, they suggest that subacute dosing might elicit a subjective clinically significant effect on MS-related spasticity, paralleling cannabinoids measurable plasma concentrations.

Effect of valproic acid on perampanel pharmacokinetics in patients with epilepsy.

We prospectively examined the effect of antiepileptic (AED) cotherapy on steady state plasma concentrations of perampanel (PMP) in epileptic patients. We classified AEDs as strong enzyme inducers (carbamazepine, phenobarbital, phenytoin, oxcarbazepine), not strong enzyme inducers/not inhibitors (levetiracetam, lamotrigine, topiramate, rufinamide, lacosamide, zonisamide, clobazam), and enzyme inhibitors (valproic acid [VPA]). The main outcome was the comparison of PMP plasma concentration to weight-adjusted dose ratio (C/D; [µg/mL]/mg kg-1  d-1 ) among comedication subgroups. From 79 patients (42 females, 37 males) aged (mean ± standard deviation) 33 ± 13 years (range = 12-66 years), 114 plasma samples were collected. Twenty-eight patients (44 samples) were cotreated with enzyme inducers (group A), 21 (27 samples) with not strong enzyme inducers/not inhibitors (group B), 21 (31 samples) with not strong enzyme inducers/not inhibitors + VPA (group C), and 9 (12 samples) with enzyme inducers + VPA (group D). PMP C/D was reduced (-56%, P < .001) in group A (1.79 ± 0.80) versus group B (4.05 ± 2.16) and increased (P < .001) in group C (6.72 ± 4.04) compared with groups A (+275%), B (+66%), and D (2.76 ± 2.00, +143%). Our study documents the unpublished higher PMP C/D in patients cotreated with VPA. These findings have both theoretical relevance, suggesting better characterization of PMP metabolic pathways with ad hoc studies, and clinical usefulness in managing patients on AED polytherapy.

Transarterial Onyx Embolization of Intracranial Dural Fistulas: A Prospective Cohort, Systematic Review, and Meta-Analysis.

BACKGROUND: Onyx is important embolic material in the endovascular treatment of intracranial dural arteriovenous fistula (DAVF). However, its impact on DAVF occlusion rates, morbidity, mortality, and complication rates is not fully examined. OBJECTIVE: To improve understanding of safety and effectiveness profiles associated with transarterial endovascular treatment using Onyx for intracranial DAVF. METHODS: We analyzed data from our prospective clinical registry and conducted a systematic review of all previous transarterial embolization studies using Onyx published between January 2005 and December 2015 in MEDLINE and EMBASE. RESULTS: In the prospective study, 41 transarterial procedures were performed in 33 consecutive patients harboring 36 DAVFs. Complete initial exclusion was obtained in 32 of 36 (88.9%) fistulas; 31 fistulas were followed up showing 4 (12.9%) recurrences. Procedure-related morbidity and mortality were 3% and 0%, respectively. The literature review identified 19 studies involving a total of 425 patients with 463 DAVFs. Meta-analysis, including our registry data, showed an initial complete occlusion rate of 82% (95% confidence interval [CI]: 74%, 88%; I2, 70.6%), and recurrence rate at midterm of 2% (95% CI: 0%, 5%; I2, 21.5%). Pooled postoperative neurological deficit, procedure-related morbidity, and mortality rates were 4% (95% CI: 2%, 6%; I2, 0%), 3% (95% CI: 1%, 5%; I2, 0%), and 0%, respectively. CONCLUSION: This meta-analysis suggests that transarterial embolization with Onyx is a safe treatment modality for DAVFs. Although Onyx showed a low recurrence rate at midterm, the long-term risk is poorly addressed in our study and should warrant a longer follow-up.

Simple and rapid validated HPLC-fluorescence determination of perampanel in the plasma of patients with epilepsy.

We present a simple and fast high-performance liquid chromatography method with fluorescence detection for the determination of the antiepileptic drug perampanel in human plasma. The chromatographic separation was performed on a Kinetex PFP (100 × 2.6 mm, 4.6 µm) column, using a mobile phase of sodium acetate 0.03 M pH 3.7 and acetonitrile (40/60, v/v), at a flow rate of 0.8 mL/min. Total chromatography time for each run was 5 min. Sample preparation (250 µL) involved only one simple precipitation step by acetonitrile spiked with mirtazapine as internal standard. The method was validated over a concentration range of 20-1000 ng/mL and successfully applied to measure perampanel concentrations in plasma samples obtained from patients with epilepsy. This assay combines the high specificity of fluorescence detection with a very simple and fast sample pretreatment and can offer real advantages over existing methods in terms of simplicity and transferability to a therapeutic drug monitoring setting.

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.

Mortality and Disability According to Baseline Blood Pressure in Acute Ischemic Stroke Patients Treated by Thrombectomy: A Collaborative Pooled Analysis.

BACKGROUND: High blood pressure (BP) is associated with worse clinical outcomes in the setting of acute ischemic stroke, but the optimal blood pressure target is still a matter of debate. We aimed to study the association between baseline BP and mortality in acute ischemic stroke patients treated by mechanical thrombectomy. METHODS AND RESULTS: A total of 1332 acute ischemic stroke patients treated by mechanical thrombectomy were enrolled (from January 2012 to June 2016) in the ETIS (Endovascular Treatment in Ischemic Stroke) registry. Linear and polynomial logistic regression models were used to assess the association between BP and mortality and functional outcome at 90 days. Highest mortality was found at lower and higher baseline systolic blood pressure (SBP) values following a J- or U-shaped relationship, with a nadir at 157 mm Hg (95% confidence interval 143-170). When SBP values were categorized in 10-mm Hg increments, the odds ratio for all-cause mortality was 3.78 (95% confidence interval 1.50-9.55) for SBP<110 mm Hg and 1.81 (95% confidence interval 1.01-3.36) for SBP≥180 mm Hg using SBP≥150 to 160 mm Hg as reference. The rate of favorable outcome was the highest at low SBP values and lowest at high SBP values, with a nonlinear relationship; in unplanned exploratory analysis, an optimal threshold SBP≥177 mm Hg was found to predict unfavorable outcome (adjusted odds ratio 0.47; 95% confidence interval 0.31-0.70). CONCLUSION: In acute ischemic stroke patients treated by mechanical thrombectomy, baseline SBP is associated with all-cause mortality and favorable outcome. In contrast to mortality, favorable outcome rate was the highest at low SBP values and lowest at high SBP values. Further studies are warranted to confirm these findings.