Predictors of outcome events and 6-year mortality after carotid endarterectomy and carotid stenting in patients with carotid artery stenosis

Aim. The aim of our study was to evaluate the results of CEA and CAS in patients with carotid artery stenosis, and their effect on long-term mortality and morbidity, as well as to identify predictors of long-term mortality in a single-centre observational study.Clinical rationale. While data on short-term morbidity and mortality after carotid endarterectomy (CEA) and carotid stenting (CAS) is robust, there is only a limited amount of literature on long-term mortality and its predictors five years-plus post these procedures.Material and methods. Consecutive patients with symptomatic and asymptomatic internal carotid artery stenosis treated with CEA or CAS in a single centre in eastern Slovakia between 2012 and 2014 were included. We recorded basic sociodemographic data, the presence of co-morbidities and periprocedural complications. Clinical and sonographic follow-up was performed three and 12 months after the procedures. Patient survival data and any stroke data was obtained at the end of a six-year follow-up.Results. We included 259 patients after CEA (mean age 67.4 ± 8.5, 64.5% men) and 321 after CAS (mean age 66.9 ± 8.4, 73.5% men). We did not identify a statistically significant difference in short-term or long-term mortality, survival times, or the presence of short-term or long-term complications between the CEA and CAS groups. Predictors of long-term mortality included age and diabetes mellitus in both cohorts. Repeated interventions were related to increased mortality only in the CAS cohort. Conclusions. The results of our study show that long-term mortality does not differ between CEA and CAS

Heart Rate Variability in evaluation of autonomic dysfunction in idiopathic REM-sleep behaviour disorder

Introduction. Nearly 80% of people diagnosed with idiopathic REM sleep behaviour disorder (iRBD) via video-polysomnography (v-PSG) are expected to be in the prodromal stage of an alpha-synucleinopathy. Signs of autonomic dysfunction can appear earlier than motor or cognitive alpha-synucleinopathy symptoms. Heart Rate Variability (HRV) can potentially be an objective measurement of autonomic dysfunction, and furthermore can be obtained directly from v-PSG.Objectives. The aim of this study was to evaluate dysautonomia in iRBD subjects using HRV obtained during different sleep stages and wakefulness from v-PSG.Material and methods. Subjects positively screened by an RBD screening questionnaire (RBD-SQ) underwent v-PSG todiagnose RBD. HRV obtained from v-PSG recordings was correlated to dysautonomia evaluated from a Non-Motor Symptoms Scale (NMSS) questionnaire. Optimal cut-off values of HRV parameters to predict dysautonomia were calculated using receiver operating characteristics (ROC) — area under the curve (AUC) analysis. The effect of confounder variables was predicted with binomial logistic regression and multiple regression analyses.Results. Out of 72 positively screened subjects, 29 subjects were diagnosed as iRBD (mean age 66 ± 7.7 years) by v-PSG. Eighty-three per cent of the iRBD subjects in our cohort were at the time of diagnosis classified as having possible or probable prodromal Parkinson’s Disease (pPD) compared to zero subjects being positively screened in the control group. The iRBD-positive subjects showed significant inverse correlations of NMSS score, particularly to log low-frequency (LF) component of HRV during wakefulness: r = –0.59 (p = 0.001). Based on ROC analysis and correlation between NMSS score, log LF during wakefulness (AUC 0.74, cut-off 4.69, sensitivity 91.7%, specificity 64.7%, p = 0.028) was considered as the most accurate predictor of dysautonomia in the iRBD group. Apnoea-hypopnoea index (AHI) negatively predicted dysautonomia in the iRBD group. None of the HRV components was able to predict the presence of iRBD in the full cohort. Age, gender, and PSG variables were significant confounders of HRV prediction.Conclusions. The presented study did not confirm the possibility of using HRV from v-PSG records of patients with iRBD to predict dysautonomia expressed by questionnaire methods. This is probably due to several confounding factors capableof influencing HRV in such a cohort

Variant recurrence confirms the existence of a FBXO31-related spastic-dystonic cerebral palsy syndrome

The role of genetics in the causation of cerebral palsy has become the focus of many studies aiming to unravel the heterogeneous etiology behind this frequent neurodevelopmental disorder. A recent paper reported two unrelated children with a clinical diagnosis of cerebral palsy, who carried the same de novo c.1000G \u3e A (p.Asp334Asn) variant in FBXO31, encoding a widely studied tumor suppressor not previously implicated in monogenic disease. We now identified a third individual with the recurrent FBXO31 de novo missense variant, featuring a spastic-dystonic phenotype. Our data confirm a link between variant FBXO31 and an autosomal dominant neurodevelopmental disorder characterized by prominent motor dysfunction

Excessive supraventricular activity and risk of atrial fibrillation in patients with cryptogenic ischaemic stroke

Introduction. Atrial fibrillation (AF) is one of the leading causes of ischaemic stroke. However, screening for AF is often time-consuming in clinical practice. Therefore, the determination of an appropriate marker to detect the presence of AF would improve the diagnostic process.Objective. The aim of the current study was to evaluate the efficacy of prolonged and early inpatient event Holter monitoring in the detection of AF in patients with ESUS-related cryptogenic ischaemic stroke (CIS), and to determine the possible relationship between excessive supraventricular activity and AF detection.Material and methods. All consecutive patients with documented cerebral or cerebellar infarction were included. The diagnostic work-up included brain neuroimaging (CT/MRI), ultrasound of the carotid and vertebral arteries, admission ECG followed by 24 hours of Holter monitoring, and transthoracic echocardiography. The 24-hour Holter ECG was analysed, and supraventricular ectopic activity (supraventricular extrasystoles, runs and pairs of supraventricular extrasystoles) was recorded in all patients. If these examinations did not reveal the cause of ischaemic stroke, the patients underwent subsequent prlonged 14-day event Holter recorder monitoring.Results. We included 48 patients (mean age 69.9 ± 8.5 years, 60.4% men) who had been diagnosed with CIS. Of these 48 patients, atrial fibrillation was detected in seven (14.6%) during the prolonged 14-day Holter event monitoring. Patients with newly diagnosed atrial fibrillation had a higher burden of supraventricular ectopic activity. The number of supraventricular extrasystoles (SVES) per hour, as well as the number of SV pairs and SV runs, was significantly higher in patients with new onset AF (p < 0.022; p < 0.043; p < 0.022).Conclusions. In our study, we confirmed that prolonged ECG event Holter monitoring in patients with CIS-ESUS subtype led to a higher rate of AF detection. Likewise, frequent supraventricular ectopic activity predicted the development of AF

Mechanochemical Solvent-Free Synthesis of Quaternary Semiconductor Cu-Fe-Sn-S Nanocrystals

In this study, we demonstrate a one-pot mechanochemical synthesis of the nanocomposite composed of stannite Cu2FeSnS4 and rhodostannite Cu2FeSn3S8 nanocrystals using a planetary ball mill and elemental precursors (Cu, Fe, Sn, S). By this approach, unique nanostructures with interesting properties can be obtained. Methods of XRD, Raman spectroscopy, UV-Vis, nitrogen adsorption, SEM, EDX, HRTEM, STEM, and SQUID magnetometry were applied. Quaternary tetragonal phases of stannite and rhodostannite with crystallite sizes 18–19 nm were obtained. The dominant Raman peaks corresponding to the tetragonal stannite structure corresponding to A-symmetry optical modes were identified in the spectra. The bandgap 1.25 eV calculated from UV-Vis absorption spectrum is very well-acceptable value for the application of the synthesized material. The SEM micrographs illustrate the clusters of particles in micron and submicron range. The formation of agglomerates is also illustrated on the TEM micrographs. Weak ferromagnetic properties of the synthesized nanocrystals were documentedPeer reviewe

Blood DNA methylation provides an accurate biomarker of KMT2B -related dystonia and predicts onset

Abstract Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1x log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (p = 0.003) – being lower in samples with late or incomplete penetrance—thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation.Abstract Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1x log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (p = 0.003) – being lower in samples with late or incomplete penetrance—thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation

Monogenic variants in dystonia: an exome-wide sequencing study

Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. Funding Else Kröner-Fresenius-Stiftung, Technische Universität München, Helmholtz Zentrum München, Medizinische Universität Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency

Functional neurological disorder in Europe : regional differences in education and health policy

Background : Functional neurological disorder (FND) is a common cause of neurological disability. Despite recent advances in pathophysiological understanding and treatments, application of this knowledge to clinical practice is variable and limited.ObjectiveOur aim was to provide an expert overview of the state of affairs of FND practice across Europe, focusing on education and training, access to specialized care, reimbursement and disability policies, and academic and patient-led representation of people with FND. Methods : We conducted a survey across Europe, featuring one expert per country. We asked experts to compare training and services for people with FND to those provided to people with multiple sclerosis (MS). Results : Responses from 25 countries revealed that only five included FND as a mandatory part of neurological training, while teaching about MS was uniformly included. FND was part of final neurology examinations in 3/17 countries, unlike MS that was included in all 17. Seventeen countries reported neurologists with an interest in FND but the estimated mean ratio of FND-interested neurologists to MS neurologists was 1:20. FND coding varied, with psychiatric coding for FND impacting treatment access and disability benefits in the majority of countries. Twenty countries reported services refusing to see FND patients. Eight countries reported an FND special interest group or network; 11 reported patient-led organizations. Conclusions : FND is largely a marginal topic within European neurology training and there is limited access to specialized care and disability benefits for people with FND across Europe. We discuss how this issue can be addressed at an academic, healthcare and patient organization level