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Background: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor disability outcome. Data on quality of life (QoL) among survivors are scarce because patients with poor-grade aSAH are underrepresented in clinical studies reporting on QoL after aSAH., Objective: To provide prospective QoL data on survivors of poor-grade aSAH to aid clinical decision making and counseling of relatives., Methods: The herniation World Federation of Neurosurgical Societies scale study was a prospective observational multicenter study in patients with poor-grade (World Federation of Neurosurgical Societies grades 4 & 5) aSAH. We collected data during a structured telephone interview 6 and 12 months after ictus. QoL was measured using the EuroQoL - 5 Dimensions - 3 Levels (EQ-5D-3L) questionnaire, with 0 representing a health state equivalent to death and 1 to perfect health. Disability outcome for favorable and unfavorable outcomes was measured with the modified Rankin Scale., Results: Two hundred-fifty patients were enrolled, of whom 237 were included in the analysis after 6 months and 223 after 12 months. After 6 months, 118 (49.8%) patients were alive, and after 12 months, 104 (46.6%) patients were alive. Of those, 95 (80.5%) and 89 (85.6%) reached a favorable outcome with mean EQ-5D-3L index values of 0.85 (±0.18) and 0.86 (±0.18). After 6 and 12 months, 23 (19.5%) and 15 (14.4%) of those alive had an unfavorable outcome with mean EQ-5D-3L index values of 0.27 (±0.25) and 0.19 (±0.14)., Conclusion: Despite high initial mortality, the proportion of poor-grade aSAH survivors with good QoL is reasonably large. Only a minority of survivors reports poor QoL and requires permanent care., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Favorable outcomes are seen in up to 50% of patients with World Federation of Neurosurgical Societies (WFNS) grade V aneurysmal subarachnoid hemorrhage. Therefore, the usefulness of the current WFNS grading system for identifying the worst scenarios for clinical studies and for making treatment decisions is limited. We previously modified the WFNS scale by requiring positive signs of brain stem dysfunction to assign grade V. This study aimed to validate the new herniation WFNS grading system in an independent prospective cohort., Methods: We conducted an international prospective multicentre study in poor-grade aneurysmal subarachnoid hemorrhage patients comparing the WFNS classification with a modified version-the herniation WFNS scale (hWFNS). Here, only patients who showed positive signs of brain stem dysfunction (posturing, anisocoric, or bilateral dilated pupils) were assigned hWFNS grade V. Outcome was assessed by modified Rankin Scale score 6 months after hemorrhage. The primary end point was the difference in specificity of the WFNS and hWFNS grading with respect to poor outcomes (modified Rankin Scale score 4-6)., Results: Of the 250 patients included, 237 reached the primary end point. Comparing the WFNS and hWFNS scale after neurological resuscitation, the specificity to predict poor outcome increased from 0.19 (WFNS) to 0.93 (hWFNS) (McNemar, P <0.001) whereas the sensitivity decreased from 0.88 to 0.37 ( P <0.001), and the positive predictive value from 61.9 to 88.3 (weighted generalized score statistic, P <0.001). For mortality, the specificity increased from 0.19 to 0.93 (McNemar, P <0.001), and the positive predictive value from 52.5 to 86.7 (weighted generalized score statistic, P <0.001)., Conclusions: The identification of objective positive signs of brain stem dysfunction significantly improves the specificity and positive predictive value with respect to poor outcome in grade V patients. Therefore, a simple modification-presence of brain stem signs is required for grade V-should be added to the WFNS classification., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02304328.

Background: Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS)., Methods: To perform a systematic review and meta-analysis of EPVS as visualized by MRI in MS. Nine out of 299 original studies addressing EPVS in humans using MRI were eligible for the systematic review and meta-analysis including a total of 457 MS patients and 352 control subjects., Results: In MS, EPVS have been associated with cognitive decline, contrast-enhancing MRI lesions, and brain atrophy. Yet, these associations were not consistent between studies. The meta-analysis revealed that MS patients have greater EPVS prevalence (odds ratio = 4.61, 95% CI = [1.84; 11.60], p = 0.001) as well as higher EPVS counts (standardized mean difference [SMD] = 0.46, 95% CI = [0.26; 0.67], p < 0.001) and larger volumes (SMD = 0.88, 95% CI = [0.19; 1.56], p = 0.01) compared to controls., Conclusions: Available literature suggests a higher EPVS burden in MS patients compared to controls. The association of EPVS to neuroinflammatory or -degenerative pathology in MS remains inconsistent. Thus, there is currently insufficient evidence supporting EPVS as diagnostic and/or prognostic marker in MS. In order to benefit future comparisons of studies, we propose recommendations on EPVS assessment standardization in MS. PROSPERO No: CRD42019133946.

Objectives: Intracranial arteriosclerotic disease is a relevant cause of ischemic stroke worldwide with a high recurrence rate despite best medical treatment. Following the SAMMPRIS trial, endovascular treatment has remained a second-line therapy. Meanwhile, there has been significant advances in device technology. SeQuent Please NEO is a novel polymer-free, drug-coated (paclitaxel/iopromide) balloon (DCB) primarily designed for cardiology. Because of its high flexibility and pushability, it may also be suitable for intracranial use. The aim of this study was to assess the feasibility and safety of SeQuent Please NEO DCB in symptomatic intracranial severe stenosis., Methods: A single-center retrospective cohort study of patients with symptomatic intracranial severe stenosis treated with SeQuent Please NEO DCB was performed at a tertiary stroke center., Results: Ten patients (all men, median age 73 years (IQR 69-77)) were included. Median pre-treatment stenosis grade was 78% (IQR 75-80%) with four internal carotid artery, two mid-basilar artery, and four vertebral artery lesions. Median post-treatment stenosis grade was 50% (IQR 45-53%). Successful angioplasty was achieved in all cases without technical failure. There were no cases of peri-procedural reocclusion and no deaths at median follow-up of 3 months (IQR 2-3)., Conclusion: In this pilot study, SeQuent Please NEO DCB was feasible and safe in the treatment of symptomatic intracranial severe stenosis. It might represent a promising alternative to medical treatment in selected cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Carotid artery stenting requires antiplatelet therapy for prevention of in-stent thrombosis. Patients suffering from acute ischemic stroke undergoing intravenous thrombolysis and emergent carotid artery stenting (eCAS) are at high risk for intracranial bleeding. We assessed efficacy and safety of acute administration of intravenous tirofiban versus aspirin in these patients., Methods: A retrospective, single center, cohort study was carried out of 32 patients who underwent eCAS (18 received tirofiban, 14 received aspirin) at our comprehensive stroke center (2008-2016)., Results: Of our 32 consecutive eCAS patients, favorable clinical outcomes (modified Rankin scale ≤ 2) were achieved in eight (47%) tirofiban patients and six (46%) aspirin patients ( p = 0.96). Overall rates were similar for symptomatic intracranial bleeding (tirofiban 22%, aspirin 29%, p = 0.68) and mortality (tirofiban 18%, aspirin 23%, p = 0.71)., Conclusions: Tirofiban and aspirin demonstrated similar efficacy and safety in thrombolyzed stroke patients who underwent eCAS in our cohort. Intravenous tirofiban with its short half-life might represent an alternative to aspirin in select patients.

An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.

Background: Intracranial atherosclerotic disease is a well-known cause of ischemic stroke. Following the SAMMPRIS trial, medical treatment is favored over stenting. Drug-eluting balloons (DEB) are widely used in coronary angioplasty, showing better results than bare-surface balloons. There is little evidence of DEB employment in intracranial stenosis, especially of paclitaxel-eluted balloons (pDEB). The Neuro Elutax SV (Aachen Resonance) is the first CE certificated pDEB for intracranial use., Objective: To compare pDEB Neuro Elutax SV (ElutaxDEB) with the Wingspan/Gateway stent system (WingspanStent)., Materials and Methods: A single-center, open-label, retrospective cohort study of 19 patients with symptomatic atherosclerotic intracranial high-grade stenosis treated with either ElutaxDEB or WingspanStent from a tertiary stroke center in Switzerland., Results: Eight patients (42%) received ElutaxDEB. Median clinical follow-up was 10 months for the WingspanStent and 9.5 months for ElutaxDEB (P=0.36). No differences were found in the clinical baseline characteristics, with a median stenosis grade of 80% for the WingspanStent and 81% for the ElutaxDEB (P=0.87). The compound endpoint 'ischemic re-event and/or restenosis' was significantly lower for ElutaxDEB (13% vs 64%; P=0.03, OR 0.08 (95% CI 0.007 to 0.93; P=0.043) than for the WingspanStent., Conclusions: The ElutaxDEB may be a promising alternative treatment for patients with symptomatic high-grade intracranial stenosis showing a significantly lower rate of ischemic re-events or restenosis in comparison with the WingspanStent-treated patients with a similar safety profile. Further studies will be needed to definitively elucidate the role of pDEB in the management of symptomatic intracranial high-grade stenosis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available., Objective: We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage., Methods: A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS)., Results: Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage., Conclusion: High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

Background and Purpose: Carotid stenosis (CS) with intraluminal carotid artery thrombus (ICAT) is rare but ominous finding. The optimal treatment modality is unclear. The aim of this study was to analyze the feasibility and outcome of acute endovascular intervention and delayed elective endovascular therapy after initial anticoagulation in these delicate cases. Moreover, both treatment points were compared and several parameters discussed to facilitate the determination of the optimal time modality in future cases., Materials and Methods: A series of 11 consecutive cases with acute symptomatic CS with ICAT that received endovascular treatment was retrospectively analyzed. General patient data, pre and post-interventional symptoms and imaging were evaluated in an overall mean follow-up of 84 weeks., Results: Urgent stenting and mechanical thrombectomy was performed in 6 patients. In the remaining 5 cases, elective endovascular treatment was planned after initial anticoagulation therapy with thrombus resolution. One case received secondary urgent treatment due to clinical deterioration. Overall outcome at three months follow-up was excellent (Modified Ranking Scale [mRS] 0-1) in 5 cases, good (mRS 2) in 4 and unfavorable in the remaining 2. Important differences between the two treatment arms were seen in 3 parameters (stenosis degree, thrombus length, and NIHSS score)., Conclusions: This is one of the largest studies analysing endovascular treatment in patients with acute symptomatic CS and additional ICAT only. Both endovascular treatment strategies seem feasible. Parameters such as size of intraluminal thrombus and clinical symptoms should be included in the decision-making process regarding the optimal individual treatment time., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

One main pathological hallmark of multiple sclerosis (MS) is demyelination. Novel therapies which enhance myelin repair are urgently needed. Insulin and insulin-like growth factor 1 (IGF-1) have strong functional relationships. Here, we addressed the potential capacity of IGF-1 and insulin to enhance remyelination in an animal demyelination model in vivo. We found that chronic intrathecal infusion of IGF-1 enhanced remyelination after lysolecithin-induced demyelination in the spinal cord of young and aged rats. Aged rats showed a weaker innate remyelination capacity and are therefore a good model for progressive MS which is defined by chronic demyelination. In contrast to IGF-1, Insulin had no effect on remyelination in either age group. Our findings highlight the potential use of IGF-1 as remyelinating therapy for MS, particularly the progressive stage in which chronic demyelination is the hallmark., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: Intravenous thrombolysis and mechanical thrombectomy predominantly using stent retrievers have been shown to effectively restore cerebral blood flow and improve functional outcome in patients with acute ischemic stroke. We sought to determine the safety and feasibility of mechanical thrombectomy using the new ERIC retrieval device., Materials and Methods: We identified 36 consecutive patients from our Stroke Center registry with acute ischemic stroke who were treated with the new ERIC retriever from September 2013 to December 2014. Patients with ischemic stroke meeting the following criteria were eligible: onset-to-treatment time of ≤4.5 hours or wake-up stroke (n = 10) with relevant CT perfusion mismatch, NIHSS score of ≥4, and proof of large-vessel occlusion in the anterior circulation on CT angiography. We assessed the baseline characteristics including age, sex, comorbidities, stroke severity, site of vessel occlusion, presence of tissue at risk, and treatment-related parameters such as onset-to-treatment time, recanalization grade, and outcome., Results: The mean age was 70 ± 13 years, and the median NIHSS score on admission was 18 (interquartile range, 10-20). Seventeen of 36 patients were on platelet inhibitors or anticoagulants before endovascular treatment (47.2%); 20 patients received intravenous thrombolysis (55.5%). The ERIC was used as the sole retriever in 28 patients (77.8%) and as a rescue device in 8. Excellent recanalization was achieved in 30/36 patients (83.3%) with TICI 3 in 19/36 and 2b in 11/36, respectively. Median procedural time in these patients was 90 minutes (interquartile range, 58-133 minutes). No intraprocedural complications occurred., Conclusions: In this observational study, the new ERIC retrieval device was technically feasible, safe, and effective in acute ischemic stroke with large-vessel occlusion., (© 2016 by American Journal of Neuroradiology.)

Purpose: To describe the use of Embozene microspheres as an alternative treatment for intracranial dural arteriovenous fistulas (DAVF)., Case Report: The DAVF was located close to the vertex and mainly fed by the left medial meningeal artery (MMA). Embolization was performed using Embozene microspheres due to stenosis in the posterior branch of the left MMA and a conglomerate of tortuous courses in the anterior branch. Complete occlusion was achieved without complication. Neurological symptoms improved, and the patient remained asymptomatic during 1-year follow-up. Angiography at 1 year did not reveal any revascularization., Conclusion: Use of microspheres may be a safe and effective alternative treatment, particularly in patients with impeded access to the DAVF., (© The Author(s) 2015.)

Stroke ranges third in mortality in industrialized nations and is the leading cause of disability in older people. Ischemic stroke following thrombotic or embolic vessel occlusion accounts for more than 80% of cerebrovascular events. Immediate restoration of cerebral blood flow is crucial in order to salvage brain tissue. Experimental thrombolytic treatment was introduced into the clinical setting in the late 1950s and required more than 30 years of intense research till its breakthrough and subsequent routine clinical use by the presentation of the NINDS trial results in 1995. To date, intravenous thrombolysis with tissue plasminogen activator up to 4.5 h after symptom onset is the only proven reperfusion therapy for acute ischemic stroke. In this review, we summarize the evolution of intravenous and intra-arterial pharmacological recanalization therapies in acute ischemic stroke and present current clinical practice as well as its promising perspectives., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Patients with medically unexplained symptoms (MUS) are difficult to treat and cause high health-care costs. Psychological interventions might be a beneficial option for treating patients with MUS, but evidence is inconsistent. This meta-analysis compares the effectiveness of psychological interventions for MUS - delivered either by psychotherapists (PTs) or by general practitioners (GPs) - with that of usual care., Method: We conducted a systematic review and meta-analysis on randomised controlled trials of psychological interventions for MUS. Physical symptoms were the primary outcome, and physical functioning and psychological symptoms were the secondary outcomes. We pooled between-group effect sizes (ESs) after the treatment and at the follow-up in random-effects meta-regressions and stratified meta-analyses. We repeated these analyses with the intervention provider, intervention dose, MUS severity and methodological quality as predictors of relative intervention effects., Results: A total of 3,225 patients in 20 studies were analysed. After the treatment, small and significant ESs were found for all 3 outcome domains (ES range: 0.13-0.19, all p < 0.05). Psychological interventions were more beneficial for physical symptoms when delivered by PTs than by GPs (p = 0.02). There was no difference between PTs and GPs in terms of physical functioning and psychological symptoms., Conclusion: Psychological interventions are effective for patients with MUS, but the effects are small and most likely of short duration. Interventions that are delivered by PTs appear to have larger effects on unexplained physical symptoms than those delivered by GPs. Whether this superiority is due to a larger number of sessions of PT interventions remains unclear from our findings.

Objective: To analyze the impact of intraoperative ultra-low-field magnetic resonance imaging (MRI) on the extent of tumor resection in nonfunctioning pituitary adenomas (NFPAs)., Methods: Retrospective analysis was performed of 104 consecutive cases undergoing intraoperative MRI-guided transsphenoidal surgery for NFPA. General patient data; endocrinologic parameters; neurologic examinations; preoperative and postoperative symptoms; preoperative, intraoperative, and postoperative imaging; and proliferation index were evaluated with an overall mean follow-up of 34 months., Results: The use of intraoperative MRI led to an increase of the overall remission rate by 52.2%, from 44.2% to 67.3%. Tumor characteristics such as size and invasiveness had an important impact on postoperative remission rate. In patients with macroadenoma and without previous pituitary surgery, a remission rate of 82.2% was achieved. Overall, the sensitivity of intraoperative MRI in the study was 32.4%. There were no false-positive interpretations. A higher proliferation index was found in the 15 patients with postoperative enlargement of residual adenomas or tumor recurrence compared with the other patients of the study group., Conclusions: This study shows that the outcome of surgical treatment of NFPAs was improved by the use of intraoperative MRI owing to more radical resection. The remission rate seems to depend on tumor characteristics. Recurrent disease might be reduced by the use of intraoperative MRI leading to more complete surgical resection of NFPAs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Object: Acromegaly is a rare disease, usually caused by a growth hormone (GH)-producing pituitary adenoma. If untreated, severe cardiovascular, metabolic, cosmetic, and orthopedic disturbances will result. Surgery is generally recommended as the first-line treatment. Transsphenoidal surgical techniques were recently extended by the introduction of intraoperative MR (iMR) imaging. In the present study, the contribution of ultra-low-field (0.15-T) iMR imaging to tumor resection, complication avoidance, and endocrinological and neurological outcome was analyzed., Methods: A series of 39 consecutive transsphenoidal iMR imaging-guided (using the PoleStar N20 device) surgical procedures performed between September 2005 and August 2009 for GH-producing pituitary adenomas was retrospectively analyzed. In addition to the patients' clinical data, the following criteria were evaluated independently: duration of surgery; length of hospital stay; endocrinological parameters; results of neurological examinations; and pre-, post-, and intraoperative MR imaging results., Results: Thirty-seven patients with acromegaly underwent 39 transsphenoidal surgeries for pituitary adenomas. During a median follow-up period of 30 months (range 9-56 months), the remission rate was 73.5% in 34 patients with primary surgery and 20% in 5 cases with previous surgery; overall the remission rate was 66.7%. There were no serious postoperative complications. Detection of tumor remnant on iMR imaging led to a 5.1% increase in remission rate., Conclusions: In this largest study to date of GH-producing pituitary adenomas in which iMR imaging-guided transsphenoidal surgery was analyzed, the results suggest that this method is a highly effective and safe treatment modality, even compared with previously published surgical series in which high-field iMR imaging was used. Limitations of iMR imaging are the detection of small residual tumor in the cavernous sinus and persisting disease that could not be observed, even on diagnostic high-field follow-up MR images. This points to a general limitation regarding remission rates that can be achieved using iMR imaging. Nevertheless, iMR imaging led to an increase of the remission rate in this study.