关键词： autoantibody   Autoimmune encephalitis   autoimmune neurological disease   encephalitis   myasthenia gravis   neuromyelitis optica   stiff person syndrome  

摘要： Autoimmune neurological diseases are an expanding group of phenotypically characteristic, potentially treatable syndromes. A number of these conditions are mediated by autoantibodies. The last decade has identified distinctive clinical clues to help diagnose these diseases, and increased clinical experience regarding the effectiveness of immunotherapies. Awareness of these conditions among non-specialists – as well as neurologists and psychiatrists – is crucial as early immunotherapy improves outcomes. To discuss the most common antibody-associated neurological conditions, we focus on autoimmune myasthenic syndromes and neuromyotonia in the peripheral nervous system, and their rapidly expanding central nervous system counterparts, which include neuromyelitis optica and autoimmune encephalitis. We also discuss other related conditions, including stiff person syndrome and classical paraneoplastic neurological syndromes. We discuss strategies for identification, differential diagnosis, investigation and treatment. Although individually these conditions are uncommon, cumulatively they form a significant group of treatable diseases that frequently present to general medicine and are important for all physicians to recognize promptly. © 2020

关键词： Hedgehog pathway   Traumatic brain injury   Neurovascular unit   Blood-brain barrier   Oxygen-glucose deprivation   Inflammation  

摘要： The homeostasis of the neurovascular unit (NVU) is disrupted after traumatic brain injury (TBI), and therapeutic strategies targeting the NVU would likely improve neurological outcomes after TBI. Sonic Hedgehog (Shh), which is an endogenous activator of the Hedgehog pathway, promotes brain repair in various injuries. In this study, the controlled cortical impact (CCI) was used to establish a moderate TBI model in adult male Sprague-Dawley rats (250-300 g), and the NVU was reconstructed in vitro from the blood-brain barrier (BBB) and neurons to investigate the effects of exogenous Shh protein on TBI. The modified neurological severity scores (mNSS) and Morris water maze tests were used to evaluate the effect of Shh on neurological function after TBI. The effect of Shh on the NVU in vivo was evaluated by detecting the degrees of cerebral edema and neuronal apoptosis. The integrity and permeability of the BBB, the level of inflammatory factors, and the expression of apoptotic proteins were detected to explore the effect of exogenous Shh on the NVU in vitro. The results showed that exogenous Shh reduced cerebral edema and neuronal apoptosis and promoted neurological recovery after TBI in rats. In vitro experiments showed that Shh-induced activation of the Hedgehog pathway promoted stability of the NVU by reducing damage to the tight junction structure and inhibiting the release of inflammatory factors and neuron apoptosis. Based on these results, the Shh-induced activation of the Hedgehog pathway might be a new promising treatment for TBI.

关键词： COVID-19   Neurological manifestations   Headache   Test and smell disorders   Muscle pain  

摘要： Introduction Neurological manifestations can occur during coronavirus disease 19 (COVID-19). Several pathogenic mechanisms have been hypothesized, without conclusive results. In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK). Methods We consecutively enrolled hospitalized COVID-19 patients. A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews. Results Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days. Headache showed tension-type features and was more frequently associated with a history of headache. Patients with ODs less frequently needed oxygen therapy. Inflammatory indices did not significantly differ between patients with and without ODs. Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache. Conclusion In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease. Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.

关键词： Machine learning   Soft-computing   Ensemble   Neurological disorders   Parkinson disease  

摘要： Parkinson disease is a neurodegenerative disorder of the central nerve system which affects body movements. The proposed technique selects best five machine learning models competitively, out of 25 state-of-the-art regression models to generate a robust ensemble. Data from 42 patients having early stage of Parkinson disease were collected which contains a total of 5875 voice recordings. Numerous state-of-the-art machine learning models have been explored to predict the motor Unified Parkinson's Disease Rating Score (UPDRS) for the collected voice measures. Evaluation parameters such as correlation, R-Square, RMSE, and accuracy have been calculated for comparative analysis. Results from the ensemble model consisting of best five models have been recalculated to analyze the prediction. K-fold validation has been incorporated to measure the robustness of ensembled model. The proposed ensemble yields UPDRS with higher accuracy of 99.6% making it well suitable to assist the diagnose for Parkinson disease.

关键词： Varicella zoster virus   Nervous system   Varicella   Herpes zoster   Encephalitis   POL III   Host genetics   Immunodeficiency  

摘要： Varicella zoster virus (VZV) is a pathogenic human herpes virus which causes varicella as a primary infection, following which it becomes latent in peripheral autonomic, sensory, and cranial nerve ganglionic neurons from where it may reactivate after decades to cause herpes zoster. VZV reactivation may also cause a wide spectrum of neurological syndromes, in particular, acute encephalitis and vasculopathy. While there is potentially a large number of coding viral mutations that might predispose certain individuals to VZV infections, in practice, a variety of host factors are the main determinants of VZV infection, both disseminated and specifically affecting the nervous system. Host factors include increasing age with diminished cell-mediated immunity to VZV, several primary immunodeficiency syndromes, secondary immunodeficiency syndromes, and drug-induced immunosuppression. In some cases, the molecular immunological basis underlying the increased risk of VZV infections has been defined, in particular, the role of POL III mutations, but in other cases, the mechanisms have yet to be determined. The role of immunization in immunosuppressed individuals as well as its possible efficacy in preventing both generalized and CNS-specific infections will require further investigation to clarify in such patients.

关键词： Central nervous system infections   SARS-CoV-2  

摘要： Background: Up to 50% of antibiotics are prescribed either unnecessarily or inappropriately in most hospitals worldwide. In the largest tertiary hospital in Singapore, patients with neurological conditions were often initiated on antibiotics for change in mental state or isolated fevers. We hypothesize that Antimicrobial Stewardship Program (ASP) interventions to discontinue empirical antibiotics in neurological patients with no clinical evidence of bacterial infection are safe. The aim of this study was to compare clinical impact and safety outcomes of ASP interventions between accepted and rejected groups. Methods: A retrospective review of the ASP database was conducted for all patients admitted to the neurology department in Singapore General Hospital between January 2014 and December 2017. Interventions were followed up and patients were classified into two intervention groups, the accepted and rejected groups. Demographic data, age-adjusted Charlson co-morbidity index, duration of antibiotic therapy, length of hospital stay post-ASP intervention (PLOS), infection-related readmissions and mortality were compared between the two groups. Data were expressed as mean +/- standard deviation for continuous variables, and unpaired Student's t-test was performed to determine intergroup differences between mean values. Results: The ASP team recommended 184 interventions, with an overall acceptance rate of 82.6% (152/184). There was no significant difference in demographics and age-adjusted Charlson co-morbidity index between the two groups. The accepted group had a shorter duration of therapy by 1.67 days (4.99 +/- 2.50 days vs. 6.66 +/- 2.34 days;P<0.01) and a shorter PLOS by 2 days, although this was not statistically significant (22.5 +/- 22.2 days vs. 24.5 +/- 51.4 days;P=0.83). There were no significant differences between the two groups in 14-day mortality and readmission rates. Conclusion: In neurological patients with no clinical evidence of bacterial infections

摘要： Another potential driver is the social determinants of health including, for example, differences in education, access to health care and resources (eg, healthy food, stable housing), health literacy, and socioeconomic status. The reasons for poor blood pressure control in these groups are poorly understood, but likely involve differences in the social determinants of health, antihypertensive medication adherence, and racism in the health-care system (eg, people of colour less often receive aggressive hypertension treatments). Better understanding of why people in some regions are at a higher risk of stroke compared with those in other regions, and why black people have more strokes than white people, is the goal of the REGARDS (REasons for Geographic and Racial Differences in Stroke) project, which is being sponsored by the National Institutes of Health until 2023.

关键词： autosis   chaperone   hypoxia-ischaemia   mitophagy   motor neuron   Parkinsonism  

摘要： In autophagy long-lived proteins, protein aggregates or damaged organelles are engulfed by vesicles called autophagosomes prior to lysosomal degradation. Autophagy dysfunction is a hallmark of several neurodegenerative diseases in which misfolded proteins or dysfunctional mitochondria accumulate. Excessive autophagy can also exacerbate brain injury under certain conditions. In this review, we provide specific examples to illustrate the critical role played by autophagy in pathological conditions affecting the brain and discuss potential therapeutic implications. We show how a singular type of autophagy-dependent cell death termed autosis has attracted attention as a promising target for improving outcomes in perinatal asphyxia and hypoxic-ischaemic injury to the immature brain. We provide evidence that autophagy inhibition may be protective against radiotherapy-induced damage to the young brain. We describe a specialized form of macroautophagy of therapeutic relevance for motoneuron and neuromuscular diseases, known as chaperone-assisted selective autophagy, in which heat shock protein B8 is used to deliver aberrant proteins to autophagosomes. We summarize studies pinpointing mitophagy mediated by the serine/threonine kinase PINK1 and the ubiquitin-protein ligase Parkin as a mechanism potentially relevant to Parkinson's disease, despite debate over the physiological conditions in which it is activated in organisms. Finally, with the example of the autophagy-inducing agent rilmenidine and its discrepant effects in cell culture and mouse models of motor neuron disorders, we illustrate the importance of considering aspects such a disease stage and aggressiveness, type of insult and load of damaged or toxic cellular components, when choosing the appropriate drug, timepoint and duration of treatment.

摘要： Background There is evidence suggesting an association between bullous pemphigoid (BP) and a range of neurological diseases. Whether neurological cancer is a risk factor for BP remains unknown. Objective The aim of the study was to investigate the risk of subsequent BP among patients with neurological cancer. Methods This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Research Database between 2000 and 2012. A total of 8313 patients with neurological cancer and 33,252 age-, sex-, and index-date-matched controls were recruited. The hazard ratio (HR) for subsequent BP in patients with neurological cancer was analyzed using a Cox model and Fine-Gray competing risk model, with mortality as the competing event. Results The incidence rates of BP per 100,000 person-years were 37.2 for patients with neurological cancer and 6.8 for controls. The crude incidence rate ratio was 5.49 (95% confidence interval [CI] 2.18-13.30). The mean time to occurrence of BP was 4.48 +/- 3.40 years for patients with neurological cancer. Neurological cancer (HR 9.65, 95% CI 3.76-24.77 for the Cox model;HR 2.41, 95% CI 1.14-5.14 for the competing risk model), age per year (HR 1.10, 95% CI 1.05-1.15 for the Cox model;HR 1.06, 95% CI 1.02-1.09 for the competing risk model), and dementia (HR 6.31, 95% CI 2.49-15.99 for the Cox model;HR 7.50, 95% CI 2.84-19.85 for the competing risk model) significantly increased the risk of BP. Conclusions Neurological cancer increased the risk for subsequent BP by 2.4-fold, with a relatively short gap of 4.5 years.