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OBJECTIVE Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13–15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14–28 days, and 3 months post-aSAH. RESULTS Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48–72 hours and 14–28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57–12.04, p = 0.01). They show better neuropsychological recovery between 48–72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09–12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14–28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

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 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.

OBJECTIVE While prior retrospective studies have suggested that delayed cerebral ischemia (DCI) is a predictor of neuropsychological deficits after aneurysmal subarachnoid hemorrhage (aSAH), all studies to date have shown a high risk of bias. This study was designed to determine the impact of DCI on the longitudinal neuropsychological outcome after aSAH, and importantly, it includes a baseline examination after aSAH but before DCI onset to reduce the risk of bias. METHODS In a prospective, multicenter study (8 Swiss centers), 112 consecutive alert patients underwent serial neuropsychological assessments (Montreal Cognitive Assessment [MoCA]) before and after the DCI period (first assessment, < 72 hours after aSAH; second, 14 days after aSAH; third, 3 months after aSAH). The authors compared standardized MoCA scores and determined the likelihood for a clinically meaningful decline of ≥ 2 points from baseline in patients with DCI versus those without. RESULTS The authors screened 519 patients, enrolled 128, and obtained complete data in 112 (87.5%; mean [± SD] age 53.9 ± 13.9 years; 66.1% female; 73% World Federation of Neurosurgical Societies [WFNS] grade I, 17% WFNS grade II, 10% WFNS grades III–V), of whom 30 (26.8%) developed DCI. MoCA z-scores were worse in the DCI group at baseline (−2.6 vs −1.4, p = 0.013) and 14 days (−3.4 vs −0.9, p < 0.001), and 3 months (−0.8 vs 0.0, p = 0.037) after aSAH. Patients with DCI were more likely to experience a decline of ≥ 2 points in MoCA score at 14 days after aSAH (adjusted OR [aOR] 3.02, 95% CI 1.07–8.54; p = 0.037), but the likelihood was similar to that in patients without DCI at 3 months after aSAH (aOR 1.58, 95% CI 0.28–8.89; p = 0.606). CONCLUSIONS Aneurysmal SAH patients experiencing DCI have worse neuropsychological function before and until 3 months after the DCI period. DCI itself is responsible for a temporary and clinically meaningful decline in neuropsychological function, but its effect on the MoCA score could not be measured at the time of the 3-month follow-up in patients with low-grade aSAH with little or no impairment of consciousness. Whether these findings can be extrapolated to patients with high-grade aSAH remains unclear. Clinical trial registration no.: NCT03032471 (ClinicalTrials.gov)

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., Scientific Reports, 9 (1), ISSN:2045-2322

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.

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.

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.

ObjectivesIntracranial 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.MethodsA 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.ResultsTen 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).ConclusionIn 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.

Background and Purpose— To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact. Methods— Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan–Meier curves. Results— Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital mortality was 13.9% (n=232). Strong independent predictors of in-hospital mortality were rebleeding (aOR, 7.69; 95% confidence interval, 3.00–19.71; P P P =0.003), and new infarction post-treatment (aOR, 2.57; 95% confidence interval, 1.43–4.62; P =0.002). Conclusions— Several—and among them modifiable—factors seem to be associated with in-hospital mortality after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming to reduce the risk of rebleeding are most promising in patients where active treatment is initially pursued. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03245866.

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.

BackgroundIntracranial 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.ObjectiveTo compare pDEB Neuro Elutax SV (ElutaxDEB) with the Wingspan/Gateway stent system (WingspanStent).Materials and methodsA 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.ResultsEight 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.ConclusionsThe 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.

Background The literature on multiple intracranial aneurysms (MIA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) focuses largely on risk factor analysis and consists essentially of retrospective cohort studies of limited sample size, or studies in populations outside Europe and North America. The purpose of this cohort study was to identify predictors for aneurysm multiplicity and to investigate the anatomic distribution of MIA in a representative Western cohort of patients with aSAH. Methods The Swiss Study of Subarachnoid Hemorrhage (SOS) database includes anonymized data from all tertiary neurovascular facilities in Switzerland. The dataset for 2009–2014 was used to compare characteristics of patients with aSAH and MIA and those with a single intracranial aneurysm (SIA) by means of descriptive and multivariate regression analysis. Results Among 1689 unselected patients with aSAH, 467 had MIA (prevalence, 27.6%). The location of the ruptured index aneurysm was correlated with the probability of finding bystander aneurysms and predicted their likely anatomic distribution. Patients with a ruptured basilar artery aneurysm (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.30–3.44) or a ruptured middle cerebral artery aneurysm (OR, 1.86; 95% CI, 1.35–2.55) were at the greatest risk for having MIA. Larger size of the index aneurysm (OR per 1 mm, 1.03; 95% CI, 1.01–1.06) was also positively correlated with aneurysm multiplicity. Males were less likely than females to have MIA (OR, 0.79; 95% CI, 0.61–1.01). Conclusions In patients with aSAH, the location of the ruptured index aneurysm is correlated with the probability of finding bystander aneurysms, and is predictive of the sites at which bystander aneurysms are most likely to be found.

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.

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.

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.

BACKGROUND: Pituitary adenomas are rare with an incidence of 0.4-8.2 per 105 inhabitants. Symptoms range from headaches to pituitary insufficiency or excessive output of hormones with associated disease. Except for prolactinomas, surgery is recommended as the first line and most effective treatment for the majority of these tumours. One of the refinements of surgical therapy introduced was intraoperative magnetic resonance imaging (iMRI). OBJECTIVE: The aim of this study was to analyse the postoperative pituitary function and the general outcome of patients treated for non-functioning and GH-producing pituitary adenomas with a transsphenoidal iMRI-assisted approach using the PoleStar™ N20 imager. METHODS: A total of 148 consecutive iMRI-guided surgeries for GH-producing and non-functioning pituitary adenomas were retrospectively analysed. Patients' clinical data, endocrinological parameters, clinical examinations and pre-/post- and intraoperative imaging studies were evaluated. RESULTS: A total of 101 patients could be classified as being in remission at follow-up; 26 (17.6%) of them due to iMRI allowing additional tumour removal. A total of 44 patients (29.7%) had more complete tumour removal because remnants were detected by iMRI. The mean hormone levels of patients did not differ significantly between pre- and postoperative examinations. There were 62 patients with preoperative, and 43 patients with postoperative pituitary insufficiency, thus, due to surgery there were 19 (12.8%) patients with improved pituitary function. CONCLUSIONS: The results show this method to be a safe and effective treatment option increasing remission rate and keeping complication rate low. Postoperative pituitary function was preserved or improved - possibly due to more exact iMRI-assisted tumour removal.

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.