Aneurysm Treatment with Woven EndoBridge-17: Angiographic and Clinical Results at 12 Months from a Retrospective, 2-Center Series.

BACKGROUND AND PURPOSE: This retrospective, 2-center study investigated the feasibility, safety, and efficacy at 12-month follow-up of the treatment of ruptured, unruptured, and recurrent intracranial aneurysms using the latest generation of the Woven EndoBridge (WEB) device, the WEB-17 system. MATERIALS AND METHODS: Aneurysms treated with WEB-17 were extracted from the databases of 2 neurovascular centers. Patients, aneurysm characteristics, complications, and clinical and anatomic results were analyzed. RESULTS: From February 2017 to May 2021, two hundred twelve patients with 233 aneurysms (181/233, 77.7%, unruptured-recurrent, and 52/233, 22.3%, ruptured) were included. High treatment feasibility (95.3%) was reported and was similar in ruptured aneurysms (94.2%) and unruptured-recurrent aneurysms (95.6%) (P = .71) and in typical (95.4%) and atypical (94.7%) locations (P = .70), but it was lower in aneurysms with an angle between the parent artery and main aneurysm axis of ≥45° (90.2%) compared with those with an angle of <45° (97.1%) (P = .03). Global mortality and morbidity were 1.9% and 3.8% at 1 month, respectively, and 4.4% and 1.9% at 12 months, respectively. One-month morbidity (P = .02) and mortality (P = .003) were higher in the ruptured group (10.0% and 8.0%, respectively) compared with unruptured-recurrent group (1.9% and 0.0%, respectively). Overall adequate occlusion (complete occlusion and neck remnant) was 86.3%. The percentage of adequate occlusion was higher (P = .05) in the unruptured-recurrent group (88.5%) compared with the ruptured group (77.5%). CONCLUSIONS: The WEB-17 system showed high feasibility for ruptured and unruptured aneurysms, typical and atypical locations, and some aneurysms with an angle of ≥45°. As the most recent generation device, the WEB-17 also demonstrates high safety and good efficacy.

[Acute and chronic toxicities associated with the use and misuse of nitrous oxide: An update]. / Toxicités aiguës et chroniques associées à l'usage et au mésusage du protoxyde d'azote : mise au point.

Nitrous oxide (N2O) is used since the eighteenth century as an anesthetic and analgesic but also for recreational use. If the labelled uses of N2O and their modalities are nowadays perfectly framed, the misuse of N2O takes very alarming proportions among teenagers and young adults. This misuse is the cause of acute (hypoxia, barotrauma, burns, neuropsychiatric disorders) and chronic complications if repeated (myeloneuropathy, anemia, thrombosis, inhalant use disorder). The main mechanism of the latter is mainly related to a functional deficit in vitamin B12 induced by N2O. The management of acute complications is symptomatic. The management of chronic complications is based on vitamin B12 supplementation. The best biomarker of chronic N2O exposure is the elevation of the plasmatic level of methylmalonic acid. In all cases of recreational misuses, addiction treatment is necessary to prevent complications or their worsening by providing information in order to stop consumption.

Fast Stent Retrieval during Mechanical Thrombectomy Improves Recanalization in Patients with the Negative Susceptibility Vessel Sign.

BACKGROUND AND PURPOSE: In acute ischemic stroke, the negative susceptibility vessel sign on T2*-weighted images traditionally highlights fibrin-rich clots, which are particularly challenging to remove. In vitro, fast stent retrieval improves fibrin-rich clot extraction. We aimed to evaluate whether the speed of stent retrieval influences the recanalization and clinical outcome of patients presenting with the negative susceptibility vessel sign. MATERIALS AND METHODS: Patients were identified from a registry of patients with ischemic stroke receiving mechanical thrombectomy between January 2016 and January 2020. Inclusion criteria were the following: 1) acute ischemic stroke caused by an isolated occlusion of the anterior circulation involving the MCA (Internal Carotid Artery-L, M1, M2) within 8 hours of symptom onset; 2) a negative susceptibility vessel sign on prethrombectomy T2*-weighted images; and 3) treatment with a combined technique (stent retriever + contact aspiration). Patients were dichotomized according to retrieval speed (fast versus slow). The primary outcome was the first-pass recanalization rate. RESULTS: Of 68 patients who met inclusion criteria, 31 (45.6%) were treated with fast retrieval. Patients receiving a fast retrieval had greater odds of first-pass complete (relative risk and 95% confidence interval [RR 95% CI], 4.30 [1.80-10.24]), near-complete (RR 95% CI, 3.24 [1.57-6.68]), and successful (RR 95% CI, 2.60 [1.53-4.43]) recanalization as well as greater odds of final complete (RR 95% CI, 4.18 [1.93-9.04]), near-complete (RR 95% CI, 2.75 [1.55-4.85]), and successful (RR 95% CI, 1.52 [1.14-2.03]) recanalization. No significant statistical differences in procedure-related serious adverse events, distal embolization, or symptomatic intracranial hemorrhage were reported. No differences were noted in terms of functional independence (RR 95% CI, 1.01 [0.53-1.93]) and all-cause mortality (RR 95% CI, 0.90 [0.35-2.30]) at 90 days. CONCLUSIONS: A fast stent retrieval during mechanical thrombectomy is safe and improves the retrieval of clots with the negative susceptibility vessel sign.

Persistent Blood Flow inside the Woven EndoBridge Device More Than 6 Months after Intracranial Aneurysm Treatment: Frequency, Mechanisms, and Management-A Retrospective Single-Center Study.

BACKGROUND AND PURPOSE: Due to its high safety and great efficacy, flow disruption with the Woven EndoBridge (WEB) device is increasingly used to treat intracranial aneurysms. We recently identified patients with intracranial aneurysm treated with the WEB who presented with residual blood flow inside the device ("contrast-in-WEB" phenomenon) more than 6 months posttreatment. This series reports the frequency and underlying mechanisms and discusses management of this phenomenon. MATERIALS AND METHODS: All patients presenting with the contrast-in-WEB phenomenon in the prospectively collected data base of patients with aneurysm treated with the WEB were retrospectively collected and analyzed. RESULTS: From June 2011 to February 2019, one hundred twenty-seven patients with 133 aneurysms were treated with the WEB and had DSA follow-up at 6 months or later. Eight patients (6.3%) presented with the phenomenon. All aneurysms were wide-neck bifurcation aneurysms, including 7 unruptured and 1 ruptured aneurysm located at the MCA (5 aneurysms), anterior communicating artery (2 aneurysms), and basilar artery (1 aneurysm). All except 1 patient received dual-antiplatelet therapy preprocedure. All except 1 patient received dual-antiplatelet therapy postoperatively for at least 1 month. The most likely mechanism of the phenomenon is the absence of intradevice thrombosis related to perioperative dual-antiplatelet medication. The phenomenon is also likely associated with a low risk of bleeding except when there is residual blood flow against the aneurysm wall or in the dome. CONCLUSIONS: Contrast-in-WEB is a relatively rare phenomenon possibly induced by dual-antiplatelet therapy continued post-WEB procedure. In most cases, no additional treatment is required.

[Interest of transcranial stimulation in pelvic and perineal disorders]. / Intérêt de la stimulation transcrânienne dans les troubles pelvi-périnéaux.

OBJECTIVE: The aim of this article was to describe the diagnostic and therapeutic value of transcranial stimulation in pelvic and perineal disorders. METHODS: A literature review (Medline database and Google scholar) with no time limit was performed using keywords: "transcranial direct stimulation", "transcranial magnetic stimulation", "neurogenic bladder", "urinary incontinence", "Parkinson disease", "multiple sclerosis", "stroke", "muscle spasticity", "pelvic pain", "visceral pain". RESULTS: Twelve articles have been selected. Transcranial magnetic or electrical stimulation is a noninvasive neuromodulation technique widely used to establish brain maps to highlight causal relationships between brain and function. Regarding pelvic-perineal disorders, repeated transcranial stimulation has shown significant effects for the treatment of overactive bladder in Parkinson's disease (P<0.05) and multiple sclerosis, but also for the treatment of refractory chronic pelvic pain (P=0.026). Finally, therapeutic effects have also been demonstrated in irritable bowel syndrome. No evidence of efficacy was found on genito-sexual disorders. CONCLUSION: Data from the literature suggest that transcranial stimulation is a noninvasive treatment that may have a role in the management of pelvic and perineal disorders. Its promising field of action would require prospective and randomized studies on a larger scale.

[Ejaculation disorders in multiple sclerosis: Prospective study of 44 patients]. / Troubles de l'éjaculation et sclérose en plaques : étude prospective de 44 patients.

INTRODUCTION: To analyze in a descriptive way the ejaculation disorders during MS and to study the correlations between dysejaculations, other sexual, urinary and anorectal disorders. MATERIAL: Prospective, monocentric, non-interventional study. Ejaculation disorders were assessed by Premature Ejaculation Profile (PEP) scores, intravaginal latency, and the Male Sexual Health Questionnaire - Ejaculation (MSHQ-Ej). The sexual disorders were evaluated by the International Index of Erectile Function (IIEF15) and the Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ). RESULTS: Forty-four men of mean age 46.8 (±10.3) years, with an average EDSS of 5.0 (±1.5) were included. According to the MSHQ-Ej score, ejaculation disorders were present in 28 out of 44 patients included (64%); 26/44 (59%) had an orgasm disorder, 23/44 (52%) a delay in ejaculation, 26/44 (59%) a decrease in ejaculation flow, 24/44 (55%) decreased ejaculated volume, 18/44 (41%) decreased ejaculation frequency, 15/44 (33%) ejaculatory pain and 11 34 (25%) showed systematic non ejaculation. The PEP score showed premature ejaculation in 14 patients (32%). The intra-vaginal latency time was less than 1minute in 6 patients (13.6%). There was a statistically significant correlation between ejaculation disorders and erectile dysfunction (P<0.05, correlation coefficient at 0.53) but no statistically significant correlation between ejaculation disorders and urinary or ano-rectal disorders. CONCLUSIONS: Dysejaculation was present in 64% of MS. These disorders were mainly characterized by a decrease in the volume of the ejaculation, the strength of ejaculation and the delay in ejaculation. LEVEL OF EVIDENCE: 4.

[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review]. / Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée.

INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

Is there a benefit of mechanical thrombectomy in patients with large stroke (DWI-ASPECTS ≤ 5)?

BACKGROUND AND PURPOSE: Whether to withhold mechanical thrombectomy when the diffusion-weighted imaging (DWI) lesion exceeds a given volume is undetermined. Our aim was to identify markers that will help to select patients with large DWI lesions [DWI-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) ≤ 5] that may benefit from thrombectomy. METHODS: From May 2010 to November 2016, 82 acute ischaemic stroke patients with DWI-ASPECTS ≤5 (43 men, 64.6 ± 14.4 years, National Institutes of Health Stroke Scale 18.4 ± 5.4) treated with state-of-the-art mechanical thrombectomy were studied. Thrombectomy alone was performed in 28 (34%) and bridging therapy in 54 (66%) patients. Recanalization was defined as a thrombolysis in cerebral infarction score 2B-3 and significant hemorrhagic transformation as parenchymal haematoma type 2 (European Cooperative Acute Stroke Study 3 classification). Pretreatment variables were compared between patients with a good (modified Rankin Scale 0-2) and a poor (modified Rankin Scale 3-6) neurological outcome at 3 months. RESULTS: Overall, 28 patients (34%) achieved good neurological outcome at 3 months. Recanalizers were significantly more likely to achieve good outcome (61% vs. 7.3%, P < 0.0001), had lower mortality (24% vs. 49%, P = 0.03) and similar rates of parenchymal haematoma type 2 (9.8% vs. 7.3%, P = 1) compared to non-recanalizers. Regression modelling identified DWI-ASPECTS >2 [odds ratio (OR) 6.93; 95% confidence interval (CI) 1.05-45.76, P = 0.04), glycaemia ≤6.8 mmol/l (OR 4.05; 95% CI 1.09-15.0, P = 0.03) and thrombolysis (OR 3.67; 95% CI 1.04-12.9, P = 0.04) as independent predictors of good neurological outcome. CONCLUSIONS: In patients with DWI-ASPECTS ≤5, two-thirds of patients experienced good neurological outcome when recanalized by state-of-the-art thrombectomy, whilst only one in 14 non-recanalizers achieved similar outcomes. Pretreatment markers of good neurological outcomes were DWI-ASPECTS >2, intravenous thrombolysis and glycaemia ≤6.8 mmol/l.

[Prospective evaluation of mouth and eye dryness induced by antimuscarinic drugs used for neurogenic overactive bladder in 35 patients with multiple sclerosis]. / Évaluation prospective de l'impact des anticholinergiques sur la sécheresse buccale et oculaire chez 35 patients atteints de sclérose en plaque avec hyperactivité vésicale neurogène.

INTRODUCTION: Mouth and eye dryness are frequently reported by patients with multiple sclerosis (MS) as side effects of antimuscarinic drugs used for neurogenic overactive bladder. We evaluated the impact of antimuscarinic drugs prescription on these symptoms. METHODS: MS patients consulting for overactive bladder were included. Xerostomia were evaluated at baseline and thirty days after treatment by self-reporting questionnaires (Xerostomia Quality of Life [X-Qol] and Xerostomia Questionnaire [XQ]), by salivary flow rate and sugar test. Xerophtalmia were evaluated by a self-reporting questionnaire (Ocular Surface Disease Index [OSDI]) and Schirmer test. Iatrogenic anticholinergic impregnation was evaluated by the Anticholinergic Drug Scale. RESULTS: From January to December 2014, 35 patients were included. Mean age was 50.1±10.2 years, mean EDSS=4.9. Mean anticholinergic impregnation was 0.6±1.0. Before treatment, none correlation was found between anticholinergic impregnation and other parameters. Twenty-two patients were evaluated after treatment. At baseline and thirty days after treatment, mean scores were respectively: 0.78±0.51 and 0.73±0.43 (P=0.67) for X-Qol, 9.22±11.8 and 7.03±11.4 (P=0.32) for XQ, 18.8±14.9 and 13.9±11.6 (P=0.06) for OSDI. Mean salivary flow rates were respectively 1.54±1.11 and 1.22±1.3 (P=0.53), positive sugar tests concerned respectively 68% and 55% of patients (P=0.53), and positive Schirmer test concerned 50% before and after treatment. CONCLUSION: Eye and mouth dryness exist in our MS population, even before prescription of antimuscarinic treatment, and is not getting worse after prescription. Those symptoms should not be the reason to stop an efficient treatment, but should be the reason to find and treat their aetiology. LEVEL OF EVIDENCE: 4.

[Anticholinergics do not affect the sexual function in women diagnosed with multiple sclerosis]. / Les anticholinergiques ne modifient pas la fonction sexuelle chez les patientes atteintes de sclérose en plaques.

AIM: Determine if the initiation of an anticholinergic treatment affects the sexual function in women diagnosed with multiple sclerosis (MS). METHODS: It was a single-centre prospective open label study on 18 women affected by MS, with a clinical overactive bladder syndrome, and examined before and after anticholinergic treatment. Several variables were studied before and after treatment: the total anticholinergic load (Anticholinergic Drug Scale [ADS]), the Female Sexual Function Index, the Urinary Symptom Profile (USP) and functional status (EDSS, MIF). Quantitative variables were analyzed using Student's test. RESULTS: Eighteen women with an average age of 48.3 years old (±10.7 years), average EDSS of 4.6 (±1.5) were examined before and after anticholinergic treatment (solifenacin and trospium). Anticholinergic load at baseline was 0.33 (±0.5) and 3.44 (±0.70) after treatment (P<0.0001). The initiation of an anticholinergic treatment allowed a significant improvement on the subscore OAB USP (10.25±4.3 to 6.22±3 P=0.01). No significant impacts of the anticholinergic load on the Female Sexual Function Index (FSFI) score (18.9±10.8 to 21.2±10.8 P=0.06) and sub-items lubrification (3.6±2.2 to 3.7±2.2 P=0.6), pain (3.6±2.5 to 4.2±2.3 P=0.4), desire (3±1.2 to 3±1.5 P=0.7), orgasm (2.7±2.1 to 3±2.4 P=0.4), satisfaction (3.9± to 4±2 p=0.9), arousal (2.9±2 to 3.3±1.8 P=0.8) was evidenced. CONCLUSION: In this limited series of "naive" patients with MS, no impact of anticholinergic therapy on vaginal lubrication or sexual quality was observed. LEVEL OF EVIDENCE: 4.

[Sympathetic skin response and multiple sclerosis: descriptive and prospective study, and association with neuroperineal disorders]. / Réponses cutanées sympathiques et sclérose en plaques : étude descriptive, prospective et association aux troubles neuropérinéaux.

OBJECTIVE: Describe the sympathetic skin responses (SSRs), reflecting the sweat activity mediated by the sympathetic nervous system, in patients with multiple sclerosis (MS) followed for urinary disorders and associate SSRs abnormalities with neuroperineal disorders. METHODS: Prospective monocentric study of a population suffering from MS, who received symptom scores (Expanded Disability Status Scale [EDSS], Urinary Symptoms Profile [USP], Neurogenic Bowel Dysfunction [NBD], International Index of Erectile Function [IIEF] and Female Sexual Function Index [FSFI]) and whose SSRs were collected from the hand palm, the foot sole and the genital skin after mechanical stimulation, before and after anticholinergic drug. RESULTS: Twenty-eight patients were included. Among them, 18 had an abolition of SSR, respectively 10, 14 and 17 at palm, perineum and foot sole. The absence of SSR was not related (P>0.05) with the duration of disease, the EDSS score, USP, IIEF15 or NBD scores. There was a statistically significant relationship between the abolition of SSR at perineum and women genitosexual disorders (P=0.01). Anticholinergic drugs remove 40 % of SSRs at hand and 67% at foot. The abolition of SSR at perineum was associated with the abolition of the SSR at sole (P=4 × 10(-5)). CONCLUSION: In these MS patients with neuroperineal disorders, more than half showed abnormal SSR. These abnormalities did not seem associated with urinary or rectal disorders but with genitosexual disorders in women. Under anticholinergic treatment, SSR frequently disappeared at palm and foot sole. LEVEL OF EVIDENCE: 4.

Optimised helper virus-free production of high-quality adeno-associated virus vectors.

BACKGROUND: Clinical development of adeno-associated virus (AAV) requires standardised, safe, efficient and scalable procedures for the manufacture of the rAAV vector, including production, purification and testing. Several strategies have been reported for the approach to the manufacturing problem. We report a helper virus-free process that produces high quality rAAV stocks. METHODS: rAAV were produced by triple transfection, a helper virus-free process. After lysis of the cells in the presence of nuclease, the rAAV produced were purified by HPLC through two ion-exchange columns in tandem followed by dialysis. rAAV stocks were thoroughly characterised for biological activity and for the presence of residual contaminants. The titer of infectious particles and of rep + particles was determined by dRA assay. Contaminating DNA and RNA were determined by fluorescent dye binding and real-time PCR. The protein content of the rAAV stocks was characterised by SDS-PAGE, ELISA test, Western blot and specific enzymatic assays for putative residual contaminating protein. The in vivo biological activity of the stocks was evaluated in mouse muscle. RESULTS: rAAV stocks obtained following this procedure elicit: 2-5 x 10(12) pp/ml; 3-6 x 10(10) ip/ml; < 10(3) rep + particles/ml; <0.3 mUeq/ml of residual benzonase activity; non-detectable Ad or beta-galactosidase proteins; <35 pg/ml of cellular genomic DNA; in vivo expression in mouse muscle without any immune reaction detected. CONCLUSIONS: This work demonstrates the possibility of producing purified high-quality rAAV free of helper virus. The procedure described in this paper is easily adaptable for large-scale production of clinical rAAV vectors.

High throughput production, screening and analysis of adeno-associated viral vectors.

Recombinant adeno-associated viruses (rAAV) are promising candidates as gene vectors, as they transduce non-dividing cells and permit lasting transgene expression in a wide spectrum of tissues. In this paper, we describe a robust procedure for the high throughput production, screening and characterization of rAAV vectors. The technology includes the production of rAAV from rapid small scale plasmid preparations and the analysis of virus productivity (physical and infectious particles) and activity (transgene expression, replication). rAAV are produced by triple transfection (rAAV plasmid and AAV- and adenovirus (Ad)-helper plasmids) on 293 human embryo kidney (HEK) cells. The titers of physical and infectious particles are obtained by dot blot hybridization and by a serial dilution assay, followed by either dot blot hybridization or real-time PCR, respectively. rAAV can be produced and characterized from plasmid mixtures containing as little as 1/100 productive molecules. Experiments on rAAV replication kinetics and Ad helper functions are discussed. All steps are performed in 96-well microtiter plates. The process is reproducible, high throughput, linear and ready for automation.