关键词： Epigenetics   DNA methylation   MeCP2   Rett syndrome   Non-neurological disorders  

摘要： Numerous neurological and non-neurological disorders are associated with dysfunction of epigenetic modulators, and methyl CpG binding protein 2 (MeCP2) is one of such proteins. Initially identified as a transcriptional repressor, MeCP2 specifically binds to methylated DNA, and mutations of MeCP2 have been shown to cause Rett syndrome (RTT), a severe neurological disorder. Recently, accumulating evidence suggests that ubiquitously expressed MeCP2 also plays a central role in non-neurological disorders including cardiac dysfunction, liver injury, respiratory disorders, urological dysfunction, adipose tissue metabolism disorders, movement abnormality and inflammatory responses in a DNA methylation dependent or independent manner. Despite significant progresses in our understanding of MeCP2 over the last few decades, there is still a considerable knowledge gap to translate the in vitro and in vivo experimental findings into therapeutic interventions. In this review, we provide a synopsis of the role of MeCP2 in the pathophysiology of non-neurological disorders, MeCP2-based research directions and therapeutic strategies for non-neurological disorders are also discussed.

关键词： Analysis   automobile driving   cognition   disabled persons   task performance  

摘要： Objective: The objective of this study was to compare the brake response time of drivers with paraplegia (who use hand control) with drivers without paraplegia (who use their feet) in a virtual driving simulator brake test. Additionally, we aimed to predict and evaluate the association of virtual brake response time with sociodemographic, motor and cognitive variables. Methods: 40 male adult drivers, with paraplegia (n = 20, mean age 38.1 +/- 3.6 years) and without paraplegia (n = 20, mean age 38.0 +/- 5.8 years), with valid driver licenses, had their brake response time evaluated in an automatic transmission car simulator. Non-disabled drivers were tested with conventional foot controls, while paraplegic drivers used hand controls. Drivers with paraplegia performed simple, choice and go/no-go reaction time tests as neuropsychological evaluations. Student's t-test was used to examine the differences of driving simulator brake response time between groups. Pearson coefficient verified the correlation of driving simulator brake response time with years of driving, length of disability, handgrip strength and neuropsychological tests of the paraplegic drivers. A regression model was developed to describe the mean of driving simulator brake response time using the backward elimination method for model adjustment selecting the explanatory variables. Results: Differences of simulator brake response time between groups were not statistically significant (non-paraplegic drivers = 0.90 seconds;paraplegic drivers = 0.92 seconds, p > 0.05). Years of driving significantly correlates with brake response time of paraplegic driver (r= -58, p = 0.009). Linear regression analyses indicated that years of schooling and years of driving (explanatory variables) explained 60.2% of driving simulator brake response time for the drivers with paraplegia. Driving simulator brake response time showed no difference between drivers with and without paraplegia. Years of driving and schooling were

关键词： Vertical laminar fractures   Coronal plane   Dural tears   Treatment   Spinal lesions  

摘要： IntroductionThe appropriate and optimal treatment for thoracic and lumbar (TL) burst fractures remains a topic of debate. Characterization of vertical laminar fractures (coronal cross-sectional imaging) is presented in this study to determine the severity and treatment options in TL burst *** retrospective evaluation of 341 consecutive patients with TL burst fractures was divided into Group I (whole), Group II (partial), and Group III (intact) based on the vertical laminar fracture morphology from coronal images on computed tomography (CT) scans. The presence of preoperative neurological status was reviewed, and several radiological parameters were measured. In addition, the incidence of dural tears was calculated in patients that underwent a decompression with posterior *** total, 270 lumbar and 71 thoracic burst fractures were analyzed. Compared with the intact group, the two other groups had significantly shorter central canal distance, wider interpedicular distance, and smaller spinal canal area, in particular, Group III. The incidences of preoperative neurological deficits in Groups I to III were 63.0, 22.2, and 6.3%, respectively. The incidences of dural tears in Groups I to III were 25.6, 6.3, and 0%, *** morphology of vertical laminar fractures observed across the coronal plane was important. Patients with "whole", "partial" and "intact" laminar fractures indicated different severity of TL burst fractures. Due to the high probability of dural tears, decompression is recommended as a primary intervention for patients with "whole" laminar fractures. However, for patients without vertical laminar fractures, minimally invasive technique might be a better choice to avoid approach-related complications.

关键词： Spinal Stenosis   Spondylosis   Ossification of Posterior Longitudinal Ligament   Neck Pain   Spinal Fusion  

摘要： BackgroundAnterior decompression with fusion (ADF) has often been performed for degenerative cervical myelopathy (DCM) in patients with poor cervical spine alignment and/or anterior cord compression. We aimed to identify clinical and radiological predictors associated with neurological recovery after *** post-hoc analysis from a prospective multicenter study included patients who were scheduled for ADF for DCM. The patients who received other surgeries (laminoplasty, posterior decompression and fusion) were excluded. The associations between baseline clinical and radiographic variables (age, sex, body mass index, etiology, cervical lordosis, range of motion, C7 slope, C2-7 sagittal vertical axis [SVA], thoracic kyphosis [TK], lumbar lordosis, sacral slope, SVA, pelvic tilt, T1 pelvic angle [TPA], the Japanese Orthopedic Association score for the assessment of cervical myelopathy [C-JOA], European Quality of Life Five Dimensions Scale [EQ-5D], Neck Disability Index [NDI], Physical Component Summary of the SF-36 [PCS], and Mental Component Summary of the SF-36) and the recovery rates as the outcome variables were investigated in the univariate regression analysis. Then, the independent predictors for increased recovery rates were evaluated using a stepwise multiple regression *** total, 37 patients completed the 1 year follow-up. The recovery rate was significantly correlated with SVA (p=0.001) and TPA (p=0.03). Univariate regression analyses showed that age (Regression coefficient =- 0.92, p=0.049), SVA (Regression coefficient =- 0.57, p=0.004) and PCS (Regression coefficient =0.80, p=0.03) score were significantly associated with recovery rate. Then, a stepwise multiple regression analysis identified the independent predictors of recovery rate after ADF as TK (p=0.01), PCS (p=0.03), and SVA (p=0.03). According to this prediction model, the following equation was obtained: recovery rate=- 8.26+1.17x(TK) - 0.45x(SVA)+0.85x(PCS) (p=0.002, R-2

关键词： Rare diseases   Patient involvement   Research themes  

摘要： BackgroundPatient involvement in research increases the impact of research and the likelihood of adoption in clinical practice. A first step is to know which research themes are important for patients. We distributed a survey on research priorities to ERN-RND members, both patient representatives and healthcare professionals, asking them to prioritize five research themes for rare neurological diseases on a scale ranging from 1 (most important) to 5 (least important). A follow-up e-mail interview was conducted with patient representatives and professionals to assess potential reasons for differences in opinions between these two *** total, 156 responses were analysed: 61 from professionals and 95 from patient representatives. They covered all ERN-RND disease groups and came from 20 different EU countries. Almost half of the respondents considered 'Developing therapies and preventive strategies' the most important research theme. In particular, patient representatives prioritized this theme more often than professionals, while professionals prioritized 'Disease mechanisms and models'. Patient representatives indicated that therapies and prevention were of the utmost importance to them, because their lives are often heavily impacted by the disease and their main goal is to relief the burden of disease. Professionals indicated that investigating disease mechanisms will lead to more knowledge and is indispensable for finding new treatments. ConclusionsPatients and professionals have different opinions on which research theme should have priority. A qualitative follow-up shows that they respect each others' view points. Different stakeholders involved in research should be aware of their differences in research theme priority. Explaining these differences to each other leads to more understanding, and could improve patient engagement in research.

关键词： Extracorporeal membrane oxygenation   V-V ECMO   Neurological complications   Respiratory failure   Cannulation   Seizure   Propensity score  

摘要： BackgroundSingle- (SL) and double-lumen (DL) catheters are used in clinical practice for veno-venous extracorporeal membrane oxygenation (V-V ECMO) therapy. However, information is lacking regarding the effects of the cannulation on neurological *** retrospective observational study based on data from the Extracorporeal Life Support Organization (ELSO) registry. All adult patients included in the ELSO registry from 2011 to 2018 submitted to a single run of V-V ECMO were analyzed. Propensity score (PS) inverse probability of treatment weighting estimation for multiple treatments was used. The average treatment effect (ATE) was chosen as the causal effect estimate of outcome. The aim of the study was to evaluate differences in the occurrence and the type of neurological complications in adult patients undergoing V-V ECMO when treated with SL or DL *** a population of 6834 patients, the weighted propensity score matching included 6245 patients (i.e., 91% of the total cohort;4175 with SL and 20,270 with DL cannulation). The proportion of patients with at least one neurological complication was similar in the SL (306, 7.2%) and DL (189, 7.7%;odds ratio 1.10 [95% confidence intervals 0.91-1.32];p=0.33). After weighted propensity score, the ATE for the occurrence of least one neurological complication was 0.005 (95% CI -0.009 to 0.018;p=0.50). Also, the occurrence of specific neurological complications, including intracerebral hemorrhage, acute ischemic stroke, seizures or brain death, was similar between groups. Overall mortality was similar between patients with neurological complications in the two *** this large registry, the occurrence of neurological complications was not related to the type of cannulation in patients undergoing V-V ECMO.

关键词： SARS-CoV-2   Anosmia   Headache   Neurology   Seizure   Stroke  

摘要： Backgrounds The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. Methods Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. Results We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%;anosmia: 41.4%;dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barre syndro

关键词： Neurological diseases   Ferroptosis   Iron   Lipid peroxide   Polyunsaturated fatty acids   Nervous system  

摘要： Ferroptosis is a newly identified form of nonapoptotic regulated cell death (RCD) characterized by irondependent accumulation of lipid peroxides which leads to oxidative stress and cell death. Recent studies have indicated that ferroptosis plays an essential role in the pathology of neurological diseases, such as intracerebral hemorrhage, ischemic stroke, epilepsy, neurodegenerative diseases, traumatic brain injury and brain cancer. This review focuses on the latest researches on the relationship of ferroptosis with nervous system diseases, highlighting the ferroptosis-based mechanisms, and elaborating the new perspective therapeutic targets of neurological disorders.

关键词： Acute intermittent porphyria   Porphyria   Cerebral vasospasm   Givosiran   Acute axonal neuropathy  

关键词： Transcriptional heterogeneity   Single cell   scRNA-seq   Neurological diseases   Neurodegenerative diseases   Huntington’   s disease   Pluripotent stem cells   Stem cell model   Smart-seq2  

摘要： Background Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained. Results Analyzing single-cell RNA sequencing from Alzheimer's disease (AD) and Huntington's disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons. We hypothesize that transcriptional heterogeneity precedes neurodegenerative disease pathologies. To test this idea experimentally, we use juvenile forms (72Q;180Q) of HD iPSCs, differentiate them into committed neuronal progenitors, and obtain single-cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy genes become more stable, while energy and actin-related genes become more variable in the mutant cells. Knocking down several differentially variable genes results in increased aggregate formation, a pathology associated with HD. We further validate the increased transcriptional heterogeneity in CHD8+/- cells, a model for autism spectrum disorder. Conclusions Overall, our results suggest that although neurodegenerative diseases develop over time, transcriptional regulation imbalance is present already at very early developmental stages. Therefore, an intervention aimed at this early phenotype may be of high diagnostic value.