Safety and effectiveness of the LVIS and LVIS Jr devices for the treatment of intracranial aneurysms: Final results of the LEPI multicenter cohort study.

BACKGROUND: The Low profile visualized intraluminal support (LVIS)/LVIS Jr is a self-expanding braiding stent for the treatment of intracranial aneurysm. This study is to determine the safety and effectiveness of the LVIS/LVIS Jr for the treatment of intracranial aneurysms in a real-world setting. METHODS: This prospective, observational, multicenter study enrolled patients with unruptured, ruptured and recanalized intracranial aneurysms treated with the LVIS stents, between February 2018 to December 2019. Primary endpoint was the cumulative morbidity and mortality rate (CMMR) assessed at 12 months follow-up (FU). RESULTS: A total of 130 patients were included (62.3 % women, mean age 55.9 ± 11.4) on an intention-to-treat basis. Four patients (3.1 %) had 2 target aneurysms; 134 total aneurysms were treated. The aneurysms were mainly located on the middle cerebral artery (41/134; 30.6 %) and the anterior communicating artery (31/134; 23.1 %). The CMMR at 1 year linked to the procedure and/or device was 4.6 % (6/130). The overall mortality was 1.5 % (2/130), none of these deaths adjudged as being linked to the procedure and/or device. All aneurysms (134/134, 100 %) were successfully treated with LVIS stent and/or other devices. At a mean FU of 16.8 months post-procedure, complete/nearly complete occlusion was achieved in 112 aneurysms (92.6 %), and only 3 patients (2.5 %) required aneurysm retreatment. CONCLUSION: This study provides evidence that the LVIS/LVIS Jr devices are safe and effective in the treatment of complex intracranial aneurysms, with very high rates of adequate occlusion at FU. These angiographic results are stable over time with an acceptable complication rate. TRIAL REGISTRATION: ClinicalTrial.gov under NCT03553771.

Endovascular Treatment of Complex Intracranial Aneurysms With LEO+ Stents: The LEO II Cohort Study.

Introduction: Stent-assisted coiling is an established treatment option for intracranial aneurysms, particularly, wide neck aneurysms with complex anatomy. The purpose of the present study was to assess the safety and efficacy of LEO+ stents in the treatment of intracranial aneurysms. Materials and Methods: A prospective, observational, multicenter study including 12 centers was performed on patients with ruptured, unruptured, and recanalized intracranial aneurysms treated with LEO+ stents. The primary efficacy endpoint was the rate of complete aneurysmal occlusion at 18 months post-procedure, and the primary safety endpoint was the morbidity and mortality at 18 months post-procedure. Results: From March 2015 to June 2017, 176 patients were enrolled (mean age of 54.8 ± 11.5 years; 65.9% women). The aneurysms were located mainly in the anterior communicating artery (29.2%) and the middle cerebral artery (28.6%). They were mostly saccular (94%), with a mean dome size of 5.3 ± 2.6 mm and a mean aspect ratio of 1.2 ± 1.0. In total, 3% of the aneurysms were treated in the acute phase of rupture. Complete/nearly complete aneurysmal occlusion and major recanalization were observed in 89% (n = 146/164) and 1.8% (n = 3/164) of patients at 18-month follow-up, respectively. The LEO+ related mortality rate was 0.6% (n = 1/170), the morbidity rate was 4.1% (n = 7/170), and these patients were mRS 0-2 at 18 months. Conclusion: Our results reflecting the use of LEO+ stents in real-world conditions confirm the efficacy and safety of LEO+ stents in the management of complex intracranial aneurysms.

Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.

BACKGROUND AND PURPOSE: The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks. METHODS: We analysed the characteristics of 2505 patients with intracranial aneurysms (IA) discovered between 2016 and 2019. Baseline characteristics, familial history of IA, tobacco and alcohol consumption, pharmacological treatments before the IA diagnosis, cardiovascular risk factors and comorbidities, headaches, allergy and atopy, IA location, absolute IA size and adjusted size ratio (aSR) were analysed with a multivariable logistic regression (MLR) model. A random forest (RF) method globally assessed the risk factors and evaluated the predictive capacity of a multivariate model. RESULTS: Among 994 patients with RIA (39.7%) and 1511 patients with UIA (60.3 %), the MLR showed that IA location appeared to be the most significant factor associated with RIA (OR, 95% CI: internal carotid artery, reference; middle cerebral artery, 2.72, 2.02-3.58; anterior cerebral artery, 4.99, 3.61-6.92; posterior circulation arteries, 6.05, 4.41-8.33). Size and aSR were not significant factors associated with RIA in the MLR model and antiplatelet-treatment intake patients were less likely to have RIA (OR: 0.74; 95% CI: 0.55-0.98). IA location, age, following by aSR were the best predictors of RIA using the RF model. CONCLUSIONS: The location of IA is the most consistent parameter associated with RIA. The use of 'artificial intelligence' RF helps to re-evaluate the contribution and selection of each risk factor in the multivariate model.

Heritability of territory of ruptured and unruptured intracranial aneurysms in families.

BACKGROUND: A previous study suggested that intracranial aneurysms are more likely to occur in the same arterial territory within families. We aimed to replicate this analysis in independent families and in a sample limited to intracranial aneurysms that ruptured. METHODS: Among families with ≥2 first-degree relatives with intracranial aneurysms, we randomly matched index families to comparison families, and compared concordance in intracranial aneurysm territory between index and comparison families using a conditional logistic events/trials model. We analyzed three European cohorts separately, and pooled the results with those of the Familial Intracranial Aneurysm study by performing an inverse variance fixed effects meta-analysis. The main analysis included both unruptured and ruptured intracranial aneurysms, and a secondary analysis only ruptured intracranial aneurysms. RESULTS: Among 70 Dutch, 142 Finnish, and 34 French families, concordance regarding intracranial aneurysm territory was higher within families than between families, although not statistically significant. Meta-analysis revealed higher concordance in territory within families overall (odds ratio [OR] 1.7, 95%CI 1.3-2.2) and for each separate territory except the anterior cerebral artery. In the analysis of ruptured intracranial aneurysms, overall territory concordance was higher within families than between families (OR 1.8; 95%CI 1.1-2.7) but the territory-specific analysis showed statistical significance only for the internal carotid artery territory. CONCLUSIONS: We confirmed that familial intracranial aneurysms are more likely to occur in the same arterial territory within families. Moreover, we found that ruptured aneurysms were also more likely to occur in the same arterial territory within families.

One-year efficacy and safety of the Trufill DCS Orbit and Orbit Galaxy detachable coils in the endovascular treatment of intracranial aneurysms: Results from the TRULINE study.

Background and purpose No series reported the mid-term results of Trufill DCS Orbit and Orbit Galaxy detachable coils with independent evaluation. We present the one-year safety and efficacy of these coils in real-life routine clinical practice. Methods A total of 167 patients with 167 aneurysms (39.1% ruptured) were enrolled in the prospective TRULINE study. The primary endpoint was the safety, assessed by the combined morbidity-mortality rate observed since the time of the procedure and up to one-year follow-up. For safety, primary analyses were performed on intent-to-treat population (attempted coils procedure) and all adverse events have been reviewed by an independent Data Safety Monitoring Board. For efficacy, primary analyses were performed on the per-protocol population (patients treated with more than 70% of Trufill coils and not retreated during the follow-up period) and an independent core laboratory evaluated angiographic results. Results At one-year post-procedure, neurologic impairment was observed in 6.5% (95% confidence interval: 3.5-11.8) of the patients, and 2.6% (95% confidence interval: 1.0-6.8) had a permanent neurological deterioration. Three deaths were observed, unrelated to the procedure or coils. At one year, complete occlusion was seen in 52 aneurysms (54.2%), neck remnant in 28 aneurysms (29.2%), and aneurysm remnant in 16 aneurysms (16.7%). During the one-year follow-up, the overall incidence of recurrence was 30.2% with a mean interval of 13.8 ± 4.5 months and the retreatment for major recanalization was needed in nine patients (6.3%). Conclusions The TRULINE study confirms that endovascular coiling with Trufill DCS Orbit and Orbit Galaxy detachable coils is safe and effective.

Young Women with a Long Past of Resistant Hypertension Cured after Surgery of Severe Bilateral Ostial Renal Artery Stenosis.

Fibromuscular dysplasia (FMD) is an underdiagnosed disease which can affect young people and with poor prognosis such as dissection or aneurysm rupture if unknown. This case illustrates a multi-vessel FMD with symptomatic severe bilateral ostial renal artery stenosis and intracranial aneurysms. One of the original features is a very late delay to diagnosis with 23 years between onset of hypertension and renal stenosis diagnosis, particularly due to lower quality of initial CT scan with milder and uncommon abnormalities. The experiment neuroradiologist had suspected the diagnosis of renal FMD because she developed intracranial aneurysms and he confirmed this diagnosis with an artery renal contrast injection during an intracranial angiogram Because of very tight and short stenosis, surgery was chosen for treatment and permitted the cure of hypertension, with normal home blood pressure after 6 months. Several particularities of FMD were presented in this case: important delay diagnosis due to rare lesion and lower sensitivity of CT in this form, the possibility to perform an angiography in high suspicion of FMD, poor prognosis risk with intracranial aneurisms and premature birth child, and the choice for surgery with cure of hypertension. We thought that hypertension etiologic evaluation must be repeated in case of resistant hypertension in young patients, particularly when they developed intracranial aneurysms.

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.

Primary cough headache, primary exertional headache, and primary headache associated with sexual activity: a clinical and radiological study.

INTRODUCTION: The purposes of this study are to describe clinical features of primary cough headache, primary exertional headache, and primary headache associated with sexual activity and to evaluate potential association with abnormalities in the cerebral or cervical venous circulation. METHODS: This multicentre, observational, non-interventional consecutive cohort study included patients fulfilling ICHD-II criteria for primary cough headache (N = 10), primary exertional headache (N = 11), or primary headache associated with sexual activity (N = 20), as well as 16 headache-free controls. Each patient was evaluated clinically and underwent craniocervical MRV of the cranial circulation. All scans were interpreted centrally by blinded raters, using the Farb criteria proposed for idiopathic intracranial hypertension. Stenosis was defined as a Farb score <3 in left or right transverse sinuses or jugular veins. RESULTS: In all primary headache groups, headaches were most frequently diffuse, severe, or very severe. Headache duration was significantly shorter in patients with cough headache (median 6.5 versus 20 and 60 min). An exploitable magnetic resonance venogram was obtained for 36 patients. Stenosis was detected in none of the control group, but in 5/7 patients with primary cough headache group, 2/10 patients with primary exertion headache, and 12/19 patients with primary headache associated with sexual activity. The frequency of stenosis was significantly different from the control group in the primary cough headache and primary headache associated with sexual activity groups. CONCLUSIONS: Headaches provoked by cough and sexual activity are possibly associated with venous abnormalities in a significant subgroup of affected patients. As the literature shows conflicting results, this venous stenosis can be considered as a promoting factor.

Effectiveness of endovascular embolization with a collagen-based embolic agent (Marsembol) in an animal model.

PURPOSE: To investigate in a porcine experimental model the effectiveness, tissue penetration, and histologic impact of renal artery embolization with a collagen-based nonadhesive embolic agent, marsembol. MATERIALS AND METHODS: Fifteen pigs underwent embolization of one interlobular artery of the renal artery with collagen-resorcinol gel emulsified with Lipiodol and further polymerized with glutaraldehyde-formaldehyde mixture. Angiograms were obtained before, during, and after the procedure. Animals were euthanized at day 0 (n = 3), 1 week (n = 3), or 3 months (n = 7), and flat-panel three-dimensional rotational radiologic images of the kidneys were obtained. Arterial, medullary, and cortical samples were taken for histologic and scanning electron microscopic investigations. RESULTS: Fifteen interlobular renal arteries were successfully embolized by delivering 1.7 mL + or - 0.2 of the embolic agent. All the embolized arteries remained occluded at 3 months, leading to a major atrophy of the embolized portions of the kidneys. Imaging and histologic findings show that the embolic agent provided a distal vessel occlusion and entirely filled the lumen of the arteries up to the glomerular tufts. The homogeneous plug formed by the embolic agent induces very few inflammatory responses. The regenerative tubular processes were arrested at 3 months. CONCLUSIONS: The collagen-based embolic agent described here has the properties required to perform embolization. These specific properties lead to very distal vessel embolization. The embolic agent is effective at 3 months in renal embolization.

Radiosurgery: operative technique, pitfalls and tips.

RATIONALE: From frame placement to dose administration, each step of the procedure must be optimized in every detail for better preservation of global precision, accuracy, safety and efficacy. METHODS: Quality control for resolution, accuracy and acquisition parameter optimization of both computed tomography (CT) scanners and magnetic resonance imaging (MRI) must be performed. Inaccuracies should then be quantified through systematic combination of MRI and CT in the radiosurgery planning system. Topography of petrous structures such as cochlea, vestibulum and facial nerve canal should be visible on the CT scan. T1-weighted volumetric MRI pulse sequences (3DT1) show a contrast-enhanced signal that is useful for both the pons interface delineation in Koos III cases, and the canal ending. High-resolution CISS T2-weighted volumetric pulse sequences (3DT2) allow direct nerve visualization and give superior stereotactic definition attributable to their better resolution minimizing partial volume effects and to their lower magnetic susceptibility minimizing distortions. The 3DT2 pulse sequences with contrast injection, show improved distinction between the pons and the nerves due to signal differences within the schwannomas. Fat saturation pulse sequences are of interest in postmicrosurgery conditions. The previous technical requirements and the dose planning elaboration will be balanced depending on the lesion volume staging (Koos), treatment history (microsurgery), clinical condition (hearing quality), pathological context (NF2) or age of the patient. The recommended marginal dose is 11-12 Gy. Tumor volume delineation allows the calculation of conformity, selectivity and gradient indexes. These global indexes must be weighted according to the relationship to critical structures and functional status of the patient. CONCLUSIONS: As an exclusively image-guided surgical method, radiosurgery requires special attention in the choice of imaging modalities and their acquisition parameters need extreme care. Technical nuances during the elaboration of the dose planning itself will directly influence both the toxicity risk and the chance of cure.

Functional cerebral venous outflow in swine and baboon: feasibility of an intracranial venous hypertension model.

INTRODUCTION: To evaluate the feasibility of performing a functional cerebral venous outflow blockage in two large animals species, the swine and the baboon, for elaboration of venous hypertension models. METHOD: Cerebral venous outflow pathways were identified on angiogram and venography of three swine and two baboons, and potential approaches to access these structures were assessed. Practicability of performing functional intracranial dural outflow blockage was tested. RESULTS: The main cerebral venous outflow route was the internal jugular vein in baboons and the paraspinal venous network in swine. Both animals had an additional venous outflow structure, the petrosquamous sinus. Access to intracranial venous sinuses was achieved through a percutaneous retrograde approach in baboon but not in swine, due to the absence of a direct connection between the dural structures and the internal jugular vein. A transcranial approach allowed to access dural venous structures in swine. In both models, partial and progressive venous sinus occlusion increased intracranial pressure, while preserving the animal's vital status. At 6 months, all animals are alive with no neurological deficits. CONCLUSION: Functional venous dural outflow blockage for elaboration of intracranial venous hypertension is feasible in both models. To be effective, the sinus blockage must be performed before the origin of the petrosquamous, an additional venous sinus seen in swine and baboon. The baboon has the greatest advantage of resembling human cerebral venous drainage, which enables an intracranial venous retrograde access. However, the transcranial approach remains a valuable option to access intracranial venous sinuses in swine.

Magnetic resonance imaging and the detection of fetal brain anomalies, injury, and physiologic adaptations.

PURPOSE OF REVIEW: Magnetic resonance imaging is playing an increasingly prominent role in depicting brain maturation, especially gyral formation that follows a temporospatial pattern, and in detecting developmental abnormalities of the cortex and other brain sectors. Knowledge of the technical advantages and limitations of in-utero magnetic resonance imaging techniques, relative to those of the postnatal period, is essential to optimize magnetic resonance sequences for early diagnosis. This includes an understanding of the changes in both brain anatomy and magnetic resonance signals that occur with an increase in gestational age. RECENT FINDINGS: Magnetic resonance imaging has evolved has an important adjunct in the diagnosis of brain malformations, particularly in the late-second or third trimester. Noxious conditions elicit more of a chronic rather than acute response in the fetal brain, which differs from that observed postnatally. Clinical applications of proton magnetic resonance spectroscopy may help elucidate fetal brain maturation and its abnormalities from a metabolic point of view. SUMMARY: Indications for fetal brain magnetic resonance imaging have increased because of improvements in magnetic resonance techniques and the ability to detect subtle changes within the cerebral parenchyma, especially in fetuses at increased risk of brain damage.

Use of a self-expanding stent with balloon angioplasty in the treatment of dural arteriovenous fistulas involving the transverse and/or sigmoid sinus: functional and neuroimaging-based outcome in 10 patients.

OBJECT: The goal of this study was to evaluate the clinical and angiography results in 10 patients with transverse-sigmoid dural arteriovenous fistulas (DAVFs) treated using sinus angioplasty and dural sinus stent insertion. METHODS: Between 2001 and 2003, 10 consecutive patients (six men and four women, age range 54-79 years) who had presented with transverse and/or sigmoid sinus DAVFs with or without sinus thrombosis underwent self-expanding stent placement and balloon angioplasty. Eight fistulas involved the transverse sinus, three the sigmoid sinus, and one the torcular and occipital sinuses. According to the Djindjian-Merland grading system, there were two Type I, five Type Ila, one Type Ilb, and two Type IV DAVFs. The mean clinical follow-up period was 21.1 months. At the last follow-up examination, seven patients were asymptomatic and three were dramatically improved. The mean angiography follow-up period was 7.5 months for the available population: four patients had complete DAVF occlusion, four had significant flow reduction, and two who experienced clinical improvement refused conventional angiography control studies. Delayed computerized tomography angiography scans were obtained to evaluate stent permeability in nine of the 10 patients. Stent permeability was demonstrated in eight of the nine patients with available control studies at a mean follow up of 20.8 months. There were two transient neurological deficits but no severe and permanent complications. CONCLUSIONS: In this series, sinus stent insertion resulted in a cure or significant clinical improvement in all patients harboring a DAVF, with no severe or permanent complication. Stent placement for transverse and/or sigmoid sinus DAVFs is a promising technique whose viability should be confirmed in larger series with longer follow-up periods.

MRS of normal and impaired fetal brain development.

Cerebral maturation in the human fetal brain was investigated by in utero localized proton magnetic resonance spectroscopy (MRS). Spectra were acquired on a clinical MR system operating at 1.5 T. Body phased array coils (four coils) were used in combination with spinal coils (two coils). The size of the nominal volume of interest (VOI) was 4.5 cm(3) (20 mm x 15 mm x 15 mm). The MRS acquisitions were performed using a spin echo sequence at short and long echo times (TE = 30 ms and 135 ms) with a VOI located within the cerebral hemisphere at the level of the centrum semiovale. A significant reduction in myo-inositol and choline and an increase in N-acetylaspartate were observed with progressive age. The normal MR spectroscopy data reported here will help to determine whether brain metabolism is altered, especially when subtle anatomic changes are observed on conventional images. Some examples of impaired fetal brain development studied by MRS are illustrated.

Diagnosis and management of vein of galen aneurysmal malformations.

Vein of Galen aneurysmal malformations (VGAM) are rare intracranial vascular anomalies typically found in children. The anatomic landmark of a VGAM is the presence of multiple arteriovenous shunts draining into a dilated median prosencephalic vein, an embryonic vessel normally absent at the adult stage. This article reviews the developmental anatomy, the clinical presentation, and the current management of VGAM.

Assessment of cortical maturation with prenatal MRI. Part I: Normal cortical maturation.

Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa.

Assessment of cortical maturation with prenatal MRI: part II: abnormalities of cortical maturation.

The fetal cortical maturation is a long process with predefined steps. Abnormalities can occur at different stages of cortical maturation, resulting in various malformations. They can result from disturbance in cell proliferation, cell differentiation, cell migration and in organization of the cortex. Analysis of the different abnormalities of cortical maturation is given with illustrations of the principal malformations encountered in utero and accessible to MRI.

MR imaging of fetal brain malformations.

METHODS: From the generally accepted data on the morphogenesis of the brain, the principles for the classification of brain malformations are given, and the salient features of each malformation which may be considered as independent from the developmental stage and therefore practical for MR imaging in the fetus after mid-gestation, are discussed. RESULTS AND DISCUSSION: However, the correlation with the clinical results in 150 cases of malformations out of a series of more than 1,000 cases of MR fetal brain imaging, demonstrates that beside the main, well-defined malformative entities, a significant degree of uncertainty remains. As the indication of further imaging is mainly based on the ultrasonographic findings, cases that are not identified as abnormal by US are not submitted to MRI (partial commissural agenesis and malformations of cortical development). A striking discrepancy exists between the findings of US and those of MRI, in the specific instance of the disorders of the posterior fossa (cystic malformations versus mega cisterna magna versus cerebellar defects), which may be only partly corrected by the use of strict anatomic criteria. Similar difficulties are observed for the diagnosis of nondestructive microcephaly. CONCLUSION: Long-term prospective longitudinal clinical-radiological studies of these groups of patients are needed.