Three patients had severe ataxia and memory impairment in a phase 1 trial of a fatty acid amide hydrolase inhibitor designed as an analgesic and antiinflammatory drug. One patient became brain dead. ...MRI of the brain showed lesions in the pons and hippocampi.
A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids.
1
FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models,
2
and some have been tested for these purposes in phase 1 and phase 2 studies.
3
Phase 3 studies were not pursued owing to a lack of efficacy. BIA 10-2474, with the chemical name 3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide, is a new reversible FAAH inhibitor. A phase 1 study was conducted in healthy volunteers to explore the safety profile of BIA 10-2474. Five of the six participants who had received the highest cumulative dose . . .
Background and purposeFlow diversion is an innovative and increasingly used endovascular treatment for intracranial aneurysms. Its initial evaluation with the first devices available showed good ...efficacy of this treatment with variable safety results. The Flow Direction Endoluminal Device (FRED) has a specific design and was evaluated in a single-arm, multicenter, prospective, Good Clinical Practice study: SAFE (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment). This analysis reports clinical results at 1 year and anatomical results at 6 months and 1 year.MethodsPatients with unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. A Clinical Event Committee and a Core Laboratory independently evaluated clinical outcome and anatomical results.ResultsThirteen interventional neuroradiology centers included 103 patients/aneurysms. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral or anterior communicating artery in 9 (8.7%), and middle cerebral artery in 8 (7.8%). Most aneurysms were small (<10 mm) in 71 patients (68.9%). Cumulative 1-year mortality and morbidity rates were 2/103 (1.9%) and 3/103 (2.9%), respectively, one death being related to cancer. At 1 year, anatomical results were: complete occlusion in 66/90 patients (73.3%), neck remnant in 7/90 patients (7.8%), and aneurysm remnant in 17/90 patients (18.9%).ConclusionsSAFE study analysis at 1 year confirms the excellent safety profile of the FRED device for aneurysm treatment, with low morbidity and mortality rates (2.9% and 1.9%, respectively) and demonstrates its efficacy (adequate occlusion in 73/90 (81.1%)).Clinical trial registrationUnique identifier: NCT02921698; Results.
In the settings of thrombectomy, the first-pass effect (FPE), defined by a complete recanalization after one pass with no rescue therapy, has been shown to be associated with an improved outcome. As ...this phenomenon has been predominantly described in anterior circulation strokes, we aimed to study the prevalence, outcomes, and predictors of FPE in patients with a basilar artery occlusion.
From a prospective multicentric registry, we collected the data of all consecutive basilar artery occlusion patients who underwent thrombectomy and compared the outcomes of patients who achieved FPE and those who did not. We also compared FPE patients with those who achieved a complete recanalization with >1 pass. Finally, a multivariate analysis was performed to determine the predictors of FPE.
Data from 280 patients were analyzed in our study, including 84 of 280 patients (30%) with an atheromatous etiology. An FPE was achieved in 93 patients (33.2%), with a significantly higher proportion of good outcomes (modified Rankin Scale score 0-2 at 3 months) and lower mortality than non-FPE patients. An FPE was also associated with improved outcomes compared with patients who went on to have full recanalization with >1 pass. Contact aspiration as first-line strategy was a strong predictor of FPE, whereas baseline antiplatelets and atheromatous etiology were negative predictors.
In our study, an FPE was achieved in approximately one-third of patients with a basilar artery occlusion and was associated with improved outcomes. More research is needed to improve devices and techniques to increase the incidence of FPE. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03776877.
Abstract
BACKGROUND
Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown high safety ...with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy WEBCAST, French Observatory, and WEBCAST-2).
OBJECTIVE
To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials.
METHODS
In a French Observatory, 2-yr clinical and anatomical data were collected. In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed. Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant.
RESULTS
The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr. The population for efficacy was 121/169 aneurysms (71.6%). Aneurysm locations were middle cerebral artery in 65/121 aneurysms (53.7%), anterior-communicating artery in 25/121 (20.7%), basilar artery in 17/121 (14.0%), and internal carotid artery terminus in 14/121 (11.6%). No clinically relevant adverse events occurred between years 1 and 2. At 2 yr, complete occlusion was observed in 62/121 (51.2%) aneurysms, neck remnant in 36/121 (29.8%) aneurysms, and aneurysm remnant in 23/121 (19.0%) aneurysms. The global retreatment rate at 2 yr was 9.3%.
CONCLUSION
This analysis confirms the high safety profile of WEB treatment at 2 yr. Aneurysm occlusion is generally stable at 2 yr, and the retreatment rate between 1 yr and 2 yr is low (2.0%).
Graphical Abstract
Graphical Abstract
BackgroundFlow disruption with the WEB is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms. Initial studies have shown a low complication rate with good ...efficacy.PurposeTo report clinical and anatomical results of the WEB treatment in the cumulative population of three Good Clinical Practice (GCP) studies: WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm), French Observatory, and WEBCAST-2.MethodsWEBCAST, French Observatory, and WEBCAST-2 are single-arm, prospective, multicenter, GCP studies dedicated to the evaluation of WEB treatment. Clinical data were independently evaluated. Postoperative and 1-year aneurysm occlusion was independently evaluated using the 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant.ResultsThe cumulative population comprised 168 patients with 169 aneurysms, including 112 female subjects (66.7%). The patients' ages ranged between 27 and 77 years (mean 55.5±10.2 years). Aneurysm locations were middle cerebral artery in 86/169 aneurysms (50.9%), anterior communicating artery in 36/169 (21.3%), basilar artery in 30/169 (17.8%), and internal carotid artery terminus in 17/169 (10.1%). The aneurysm was ruptured in 14/169 (8.3%). There was no mortality at 1 month and procedure/device-related morbidity was 1.2% (2/168). At 1 year, complete aneurysm occlusion was observed in 81/153 aneurysms (52.9%), neck remnant in 40/153 aneurysms (26.1%), and aneurysm remnant in 32/153 aneurysms (20.9%). Re-treatment was carried out in 6.9%.ConclusionsThis series is at the moment the largest prospective, multicenter, GCP series of patients with aneurysms treated with WEB. It shows the high safety and good mid-term efficacy of this treatment.Clinical trial registrationFrench Observatory: Unique identifier (NCT18069); WEBCAST and WEBCAST-2: Unique identifier (NCT01778322).
Objectives
To compare 3D-TOF magnetic resonance angiography (MRA) and contrast-enhanced MRA (CE-MRA) sequences at 3T in the follow-up of coiled aneurysms with digital subtracted angiography (DSA) as ...the gold standard.
Methods
DSA, 3D-TOF and CE-MRA were performed in a prospective series of 126 aneurysms in 96 patients (57 female, 39 male; age: 25–75 years, mean: 51.3 ± 11.3 years). The quality of aneurysm occlusion was assessed independently and anonymously by a core laboratory.
Results
Using DSA (gold standard technique), total occlusion was depicted in 57 aneurysms (45.2%), neck remnant in 34 aneurysms (27.0%) and aneurysm remnant in 35 aneurysms (27.8%). Sensitivity, specificity, positive predictive value and negative predictive value were very similar with 3D-TOF and CE-MRA. Visibility of coils was much better with 3D-TOF (95.2%) than with CE-MRA (23.0%) (
P
< 0.001). Also, substantial artefacts were less frequent with 3D-TOF (4.0%) than with CE-MRA (11.9%;
P
= 0.012).
Conclusions
In this large prospective series of patients with coiled aneurysms, at 3T 3D-TOF MRA was equivalent to CE-MRA for the evaluation of aneurysm occlusion, but coil visibility was superior at 3D-TOF. Thus the use of 3D-TOF at 3T is recommended for the follow-up of coiled intracranial aneurysms.
Key Points
• Different Magnetic Resonance (MR) imaging techniques are used to evaluate intracranial aneurysms.
•
At 3T MR, 3D-TOF and CE-MRA appear equivalent for evaluating coiled aneurysms..
•
Coils are better visualised on 3D-TOF than on CE-MRA.
•
Combined analysis of 3D-TOF and CE-MRA does not seem helpful.
•
At 3T, 3D-TOF techniques are recommended for monitoring patients with coiled aneurysms.
The aim of the present study was to compare patients displaying chronic and treatment-resistant depression with healthy controls, using the resting-state perfusion with arterial spin labeling (ASL) ...perfusion magnetic resonance imaging (MRI) technique at 3T. The study focused on the subgenual anterior cingulate cortex (sACC), which is a key component in the pathophysiology of depression. Six patients with chronic and treatment-resistant depression and six healthy control subjects were included. ASL is an innovative imaging technique which sidesteps the limitations of other functional neuroimaging techniques (functional MRI, positron emission tomography). A statistical analysis of perfusion maps was performed using SPM2 software. Statistically significant hyperperfusion regions were found in the depressed patient group compared with the healthy control group in the following: the bilateral sACC, left prefrontal dorsomedian cortex, left ACC and left subcortical areas (putamen, pallidum and amygdala). This study confirmed the involvement of the sACC in depression, particularly chronic and treatment-resistant depression, using ASL at 3T, a safe perfusion technique that seems to be appropriate for investigating functional abnormalities in psychiatric disorders.
After demonstrating the relative preservation of fruit and vegetable knowledge in patients with semantic dementia (SD), we sought to identify the neural substrate of this unusual category effect. ...Nineteen patients with SD performed a semantic sorting task and underwent a morphometric 3T MRI scan. The grey-matter volumes of five regions within the temporal lobe were bilaterally computed, as well as those of two recently described areas (FG1 and FG2) within the posterior fusiform gyrus. In contrast to the other semantic categories we tested, fruit and vegetable scores were only predicted by left FG1 volume. We therefore found a specific relationship between the volume of a subregion within the left posterior fusiform gyrus and performance on fruits and vegetables in SD. We argue that the left FG1 is a convergence zone for the features that might be critical to successfully sort fruits and vegetables. We also discuss evidence for a functional specialization of the fusiform gyrus along two axes (lateral medial and longitudinal), depending on the nature of the concepts and on the level of processing complexity required by the ongoing task.
•We studied the neural substrate of fruit & vegetable knowledge in semantic dementia.•This knowledge is linked to left FG1 volume (subregion of posterior fusiform gyrus).•The left FG1 might be a convergence zone for the features of fruits and vegetables.•We provide evidence for the functional specialization of the fusiform gyrus.
The WEB is an innovative flow disruption device for cerebral aneurysm embolization with rapidly expanding indications. Our purpose was to evaluate the diagnostic performance of computed tomography ...angiography (CTA) at 1-year follow-up of aneurysms treated with the WEB.
Between April 2014 and May 2016, the study prospectively included patients treated with the WEB at our institution, and followed up within 24hours by CTA and at 1year by CTA, time-of-flight magnetic resonance angiography (TOF MRA) and digital subtraction angiography (DSA). The diagnostic quality of imaging data was assessed based on the confidence index, artifacts, and WEB shape depiction. The imaging diagnostic performance was assessed using 3 criteria at 1year: aneurysm occlusion status and worsening, and WEB shape compression. Interobserver and intermodality agreement was determined by calculating κ values.
The study ultimately included 16 patients (9 women, mean age 53±7.6years). CTA quality confidence was scored as 2/2, artifacts 0.4/2 and WEB shape depiction 1.9/2, superior to TOF MRA for the latter two criteria. Aneurysm occlusion was adequate in 93.7% of patients, with CTA showing excellent interobserver reproducibility and agreement with DSA on a 4-grade scale (κ=1.00), while TOF MRA yielded good reproducibility (κ=0.76) and agreement with DSA (κ=0.69). CTA also identified aneurysm occlusion worsening (43.7%) and WEB compression (81.2%) in excellent agreement with DSA (κ=0.85 and 1.00).
CTA is a reproducible and reliable technique for the follow-up of aneurysms treated with the WEB device.
PDF
