关键词： Next generation sequencing   Neurogenetics   Neurology   Neurodegenerative   Diagnosis  

摘要： Currently there is no secured ongoing funding in Australia for next generation sequencing (NGS) such as exome sequencing (ES) for adult neurological disorders. Studies have focused on paediatric populations in research or highly specialised settings, utilised standard NGS pipelines focusing only on small insertions, deletions and single nucleotide variants, and not explored impacts on management in detail. This prospective multi-site study performed ES and an extended bioinformatics repeat expansion analysis pipeline, on patients with broad phenotypes (ataxia, dementia, dystonia, spastic paraparesis, motor neuron disease, Parkinson's disease and complex/not-otherwise-specified), with symptom onset between 2 and 60 years. Genomic data analysis was phenotype-driven, using virtual gene panels, reported according to American College of Medical Genetics and Genomics guidelines. One-hundred-and-sixty patients (51% female) were included, median age 52 years (range 14-79) and median 9 years of symptoms. 34/160 (21%) patients received a genetic diagnosis. Highest diagnostic rates were in spastic paraparesis (10/25, 40%), complex/not-otherwise-specified (10/38, 26%) and ataxia (7/28, 25%) groups. Findings were considered 'possible/uncertain' in 21/160 patients. Repeat expansion detection identified an unexpected diagnosis of Huntington disease in an ataxic patient with negative ES. Impacts on management, such as more precise and tailored care, were seen in most diagnosed patients (23/34, 68%). ES and a novel bioinformatics analysis pipepline had a substantial diagnostic yield (21%) and management impacts for most diagnosed patients, in heterogeneous, complex, mainly adult-onset neurological disorders in real-world settings in Australia, providing evidence for NGS and complementary multiple, new technologies as valuable diagnostic tools.

关键词： Neurology   Education   Residents   Global health   Telemedicine   Exchange  

摘要： There is considerable heterogeneity in residency education around the world. The Neurology International Residents Videoconference and Exchange (NIRVE) program aims to deliver neurology educational content to residents across different resource settings and countries through a monthly videoconferencing platform. Its purpose is to fill gaps in didactic teaching, increase exposure to a variety of cases including various practices and delivery of neurology in multiple countries, as well as integrate global health content into neurology education. NIRVE also facilitates resident exchanges among participating sites. In this descriptive article, we report NIRVE's structure and its cumulative productivity. Since its creation, NIRVE has held more than 90 videoconference rounds and has connected 16 sites in North America, South America, Europe, Asia and Africa. We describe challenges encountered since the inception of the program eleven years ago. NIRVE also fosters a culture of longterm international connection and collaboration. During global disease outbreaks, such as the current COVID-19 pandemic, videoconference rounds serve as a sustainable alternative means to deliver education. Future goals include increasing the number of sites involved, including a focus on Africa and Asia, and fostering resident-led advocacy projects.

关键词： COVID-19   Multiple sclerosis   Neuromuscular disorders   Autoimmune disease   Immunosuppressive therapies   Neurological disorders  

摘要： Objective: To study the risk of acquiring Corona Virus Disease 2019 (COVID-19) and its outcomes in patients on immunosuppressive therapy (IST) for chronic autoimmune neuromuscular disorders (aNMD) and multiple sclerosis (MS). Methods: We used TriNetX, a global health collaborative clinical research platform collecting real-time electronic medical records data, which has one of the largest known global COVID-19 database. We included patients with chronic autoimmune neuromuscular disorders (aNMD) [myasthenia gravis (MG), inflammatory myositis, and chronic inflammatory neuropathies (CIN)] and MS, based on the International Classification of Disease-10 (ICD-10) coding for one year before January 20th, 2020. We examined the use of IST, rate of COVID-19, hospitalization, intubation, and mortality among the patients with aNMD and MS. Results: A total of 33,451 patients with aNMD and 42,899 patients with MS were included. Among them, 111 (0.33%) patients with aNMD and 115 patients (0.27%) with MS had COVID-19. About one third of them required hospitalization. IST did not appear to have a significant impact on overall infection risk in either group;however, risk of hospitalization for immunosuppressed patients with aNMD was higher (Odds ratio 2.86, p-value 0.011). Conclusions: IST use does not appear to make patients with aNMD and MS more vulnerable to COVID-19. IST may be continued during the pandemic, as previously suggested by expert opinion guidelines. However, it is important to consider individualizing immunotherapy regimens in some cases. Additional physician reported registry-based data is needed to further confirm these findings.

关键词： Brain diseases   Nervous system diseases   Meta-analysis   Systematic review   Umbrella review   Risk factors   Protective factors  

摘要： Background: The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases. Methods: We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified. Results: We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis an

关键词： transcriptomics   single-cell RNA sequencing   cerebrospinal fluid   COVID-19   SARS-CoV-2   neurological manifestation   Neuro-COVID   T cell exhaustion   interferon-stimulated genes  

摘要： Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache and neuroinflammatory or cerebrovascular disease. These conditions termed here as Neuro-COVID are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared with patients with non-inflammatory and auto-immune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4(+) T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature;however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared with mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.

关键词： Dopaminergic signalling   Brain development   Mental disorders  

摘要： Dopamine (DA), a critical neurotransmitter of both the central and peripheral nerve system, plays important roles in a series of biological processes. Dysfunction of dopaminergic signalling may lead to a series of developmental disorders, including attention deficit/hyperactivity disorder, autism and schizophrenia. However, the exact roles of dopaminergic signalling in these diseases are far from fully understood. We analyse the roles of dopaminergic signalling in multiple physiological and pathological processes, focusing on brain development and related disorders. By summarizing current research in this area, we provide guidance for future studies. This review seeks to deepen our understanding of dopaminergic signalling in developmental disorders, which may offer clues for developing more effective therapeutic drugs.

关键词： Pediatric   Neurology   Readmission   Predictors   Indicators  

摘要： Background Unplanned readmission is one of many measures of the quality of care of pediatric patients with neurological conditions. In this multicenter study, we searched for novel risk factors of readmission of patients with neurological conditions. Methods We retrieved hospitalization data of patients less than 18 years with one or more neurological conditions. This resulted in a total of 105,834 encounters from 18 hospitals. We included data on patient demographics, prior healthcare resource utilization, neurological conditions, number of other conditions/diagnoses, number of medications, and number of surgical procedures performed. We developed a random intercept logistic regression model using stepwise minimization of Akaike Information Criteria for variable selection. Results The most important neurological conditions associated with unplanned pediatric readmissions include hydrocephalus, inflammatory diseases of the central nervous system, sleep disorders, disease of myoneural junction and muscle, other central nervous system disorder, other spinal cord conditions (such as vascular myelopathies, and cord compression), and nerve, nerve root and plexus disorders. Current and prior healthcare resource utilization variables, number of medications, other diagnoses, and certain inpatient surgical procedures were associated with changes in odds of readmission. The area under the receiver operator characteristic curve (AUROC) on the independent test set is 0.733 (0.722, 0.743). Conclusions Pediatric patients with certain neurological conditions are more likely to be readmitted than others. However, current and prior healthcare resource utilization remain some of the strongest indicators of readmission within this population as in the general pediatric population.

关键词： Kynurenine   Neurotransmitter   Pterin   LC-MS/MS   Serum   CSF  

摘要： Concurrent measurement of tyrosine, tryptophan and their metabolites, and other co-factors could help to diagnose and better understand a wide range of metabolic and neurological disorders. The two metabolic pathways are closely related to each other through co-factors, regulator molecules and enzymes. By using high performance liquid chromatography coupled to electrospray ionization triple quadrupole mass spectrometry, we present a robust, selective and comprehensive method to determine 30 molecules within 20 min using a Waters Atlantis dC18. The method was validated according to the guideline of European Medicines Agency on bioanalytical method validation. Analytical performance met all the EMA requirements and the assay covered the relevant clinical concentrations. Linear correlation coefficients were all > 0.998. Intra-day and inter-day accuracy were between 80-119% and 81-117%, precision 1-19% respectively. The method was applied to measure TYR, TRP and their metabolites, and other neurologically important molecules in human serum and CSF samples. The assay can facilitate the diagnosis and is suitable for determination of reference values in clinical laboratories. (C) 2020 Elsevier B.V. All rights reserved.

关键词： Congenital heart disease   Aortic coarctation   Neurological complications   Stroke   Subarachnoid bleeding   Mortality  

摘要： Background: Patients with coarctation of the aorta (CoA) are at increased risk of periprocedural and late neurological complications. Based on a nationwide inpatient dataset, we assessed the prevalence and risk factors for neurological complications in this cohort. Method and Results: We included all CoA patients hospitalized in England between 1997 and 2015. The risk for procedural complications, subarachnoid bleeding and ischemic stroke were quantified, and risk factors investigated. Overall, 11,907 patients (60% male) with CoA were identified. The median age at first presentation was 0.6 years with a median follow-up period of 14.4 years. Throughout the study period, 8456 surgical or interventional procedures were performed in 6796 patients. The neurological complication rate for primary surgical or interventional repair in patients born after 1997 was 0.05% and 0.2%, respectively. During a total follow-up period of 146,295 patient-years, late neurological complications such as subarachnoid bleeding and cerebral infarction occurred in 225 patients (0.15%/patient-year). The median age for subarachnoid bleeding was 29 years and 57 years for ischemic stroke. While, arterial hypertension (p = .0014), current smoking (p = .02), dyslipidaemia (p = .007) and diabetes (p = .037) were significantly related to the risk of ischemic stroke, only arterial hypertension emerged as significant risk factor for subarachnoid bleeding. Conclusions: Neurological complication during primary CoA repair are extremely rare in the current era. In contrast, many CoA patients are afflicted by late complications such as subarachnoid bleeding and ischemic stroke at a relatively young age, emphasizing the need for meticulous and pro-active blood pressure control and reduction of cardiovascular risk factors. (C) 2020 Published by Elsevier B.V.

关键词： 北京大学出版社   文献计量学   《中文核心期刊要目总览》   核心期刊   神经病学   精神病学   专家评审   中华神经医学杂志  

摘要： 《中华神经医学杂志》主编:我们谨此郑重通知:依据文献计量学的原理和方法,经研究人员对相关文献的检索、统计和分析,以及学科专家评审,贵刊《中华神经医学杂志》入编《中文核心期刊要目总览》2017年版(即第8版)之“神经病学与精神病学”类的核心期刊。该书由北京大学出版社出版。