关键词： Coccidioidal meningitis   Non-HIV/AIDS   CNS   Neurological center   Mexico  

摘要： Background: Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. Objective: To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. Results: The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 +/- 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm(3). The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. Conclusions: Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than twothirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

关键词： Fibrillar aggregates   Metal ion toxicity   Neurodegeneration   Serum albumin  

摘要： Protein fibrillation is a leading cause of innumerable neurodegenerative diseases. The exact underlying mechanism associated with the formation of fibrils is yet to be known. Recently, the role of metal ions resulting into fibrillation of proteins has gained attention of the scientific community. In this piece of work, we have investigated the effect of the aluminum (Al) metal ion on the kinetics of aggregation of bovine serum albumin (BSA) protein under physiological conditions by employing several biophysical and microscopic techniques. Quenching of tryptophan fluorescence was observed along with 9 nm blue shift, demonstrating BSA becomes more hydrophobic during unfolding pathway of thermal denaturation. Moreover, ANS (8-Anilino-1-naphthalene sulfonic acid) binding shows quenching in fluorescence intensity with increasing time of incubation at 65 degrees C, suggesting unfolding leading to the disruption of hydrophobic patches in BSA. Besides, Thioflavin T intensity indicated a significant acceleration in BSA fibrillation at a ratio of 1:1 and 1:2 of BSA and Al (III) metal ion respectively. In addition, circular dichroism (CD) spectroscopy study revealed the transition of BSA from alpha-helical conformation to the beta-sheet rich structure. Molecular docking analysis demonstrated significant binding affinity (-1.2 kcal/mol) of Al (III) with BSA involving Phe501, Phe506, Val575, Thr578, Gln579, Leu531 residues. Transmission electron microscopy (TEM) reaffirm augmentation of thermal-induced BSA fibril formation in the presence of Al (III) metal ions. This study highlights the metal chelating potency as the possible therapeutic target for neurological diseases. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of King Saud University.

关键词： Multiple sclerosis   Neurological disorders   SARS-CoV-2  

摘要： The coronavirus disease 2019 (COVID-19) pandemic is concerning for patients with neuroimmunological diseases who are receiving immunotherapy. Uncertainty remains about whether immunotherapies increase the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or increase the risk of severe disease and death upon infection. National and international societies have developed guidelines and statements, but consensus does not exist in several areas. In this Review, we attempt to clarify where consensus exists and where uncertainty remains to inform management approaches based on the first principles of neuroimmunology. We identified key questions that have been addressed in the literature and collated the recommendations to generate a consensus calculation in a Delphi-like approach to summarize the information. We summarize the international recommendations, discuss them in light of the first available data from patients with COVID-19 receiving immunotherapy and provide an overview of management approaches in the COVID-19 era. We stress the principles of medicine in general and neuroimmunology in particular because, although the risk of viral infection has become more relevant, most of the considerations apply to the general management of neurological immunotherapy. We also give special consideration to immunosuppressive treatment and cell-depleting therapies that might increase susceptibility to SARS-CoV-2 infection but reduce the risk of severe COVID-19. In this Review, the authors synthesize recommendations on the management of neuroimmunological disease in the context of the COVID-19 pandemic. They consider these recommendations alongside the first available data from patients, and provide an overview of management approaches in the COVID-19 era.

关键词： cardiac arrest   cardiopulmonary resuscitation (CPR)   neurological function   prediction model  

摘要： Background Cardiac arrest is still a global public health problem at present. The neurological outcome is the core indicator of the prognosis of cardiac arrest. However, there is no effective means or tools to predict the neurological outcome of patients with coma and survived 24 hours after successful cardiopulmonary resuscitation (CPR). Hypothesis Therefore, we expect to construct a prediction model to predict the neurological outcome for patients with coma and survived 24 hours after successful CPR. Methods A retrospective cohort study was used to construct a prediction model of the neurological function for patients with coma and survived 24 hours after successful CPR. From January 2007 to December 2015, a total of 262 patients met the inclusion and exclusion criteria. Results The predictive model was developed using preselected variables by a systematic review of the literature. Finally, we get five sets of models (three sets of construction models and two sets of internal verification models) which with similar predictive value. The stepwise model, which including seven variables (age, noncardiac etiology, nonshockable rhythm, bystander CPR, total epinephrine dose, APTT, and SOFA score), was the simplest model, so we choose it as our final predictive model. The area under the ROC curve (AUC), specificity, and sensitivity of the stepwise model were respectively 0.82 (0.77, 0.87), 0.72and 0.82. The AUC, specificity, and sensitivity of the bootstrap stepwise (BS stepwise) model were respectively 0.82 (0.77, 0.87), 0.71, and 0.82. Conclusion This new and validated predictive model may provide individualized estimates of neurological function for patients with coma and survived 24 hours after successful CPR using readily obtained clinical risk factors. External validation studies are required further to demonstrate the model's accuracy in diverse patient populations.

关键词： ABC transporters   Blood-brain barrier (BBB)   Neurodegenerative diseases   P-glycoprotein (P-gp)   Breast cancer resistance protein (BCRP)   Multidrug resistance-associated proteins (MRPs)  

摘要： ABC (ATP-binding cassette) transporters represent one of the largest and most diverse superfamily of proteins in living species, playing an important role in many biological processes such as cell homeostasis, cell signaling, drug metabolism and nutrient uptake. Moreover, using the energy generated from ATP hydrolysis, they mediate the efflux of endogenous and exogenous substrates from inside the cells, thereby reducing their intracellular accumulation. At present, 48 ABC transporters have been identified in humans, which were classified into 7 different subfamilies (A to G) according to their phylogenetic analysis. Nevertheless, the most studied members with importance in drug therapeutic efficacy and toxicity include P-glycoprotein (P-gp), a member of the ABCB subfamily, the multidrug-associated proteins (MPRs), members of the ABCC subfamily, and breast cancer resistance protein (BCRP), a member of the ABCG subfamily. They exhibit ubiquitous expression throughout the human body, with a special relevance in barrier tissues like the blood-brain barrier (BBB). At this level, they play a physiological function in tissue protection by reducing or limiting the brain accumulation of neurotoxins. Furthermore, dysfunction of ABC transporters, at expression and/or activity level, has been associated with many neurological diseases, including epilepsy, multiple sclerosis, Alzheimer's disease, and amyotrophic lateral sclerosis. Additionally, these transporters are strikingly associated with the pharmacoresistance to central nervous system (CNS) acting drugs, because they contribute to the decrease in drug bioavailability. This article reviews the signaling pathways that regulate the expression and activity of P-gp, BCRP andMRPs subfamilies of transporters, with particular attention at the BBB level, and their mis-regulation in neurological disorders. (C) 2020 Elsevier Inc. All rights reserved.

关键词： Probiotic supplementation   Inflammation   Oxidative stress   Neurological disorders   Meta-analysis  

摘要： Background and objective: The objective of meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of probiotic supplementation on metabolic status in patients with neurological disorders. Methods: The following databases were search up to April 2019: Pubmed, Scopus, Google scholar, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 % Confidence Intervals (95 % CI). Results: Nine studies were included in this meta-analysis. The findings suggested that probiotic supplementation resulted in a significant reduction in C-reactive protein (CRP) [Weighted Mean Difference (WMD): -1.06;95 % CI: -1.80, -0.32] and malondialdehyde (MDA) levels (WMD: -0.32;95 % CI: -0.46, -0.18). Supplementation with probiotics also significantly reduced insulin (WMD: -3.02;95 % CI: -3.88, -2.15) and homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.71;95 % CI: -0.89, -0.52). Probiotics significantly reduced triglycerides (WMD: -18.38;95 % CI: -25.50, -11.26) and VLDL-cholesterol (WMD: -3.16;95 % CI: -4.53, -1.79), while they increased HDL-cholesterol levels (WMD: 1.52;95 % CI: 0.29, 2.75). Conclusion: This meta-analysis demonstrated that taking probiotic by patients with neurological disorders had beneficial effects on CRP, MDA, insulin, HOMA-IR, triglycerides, VLDL-cholesterol and HDL-cholesterol levels, but did not affect other metabolic parameters.

关键词： Breaking bad news   Diagnosis communication   Neurodegenerative conditions   Motor neurone disease   Multiple sclerosis   Parkinson's disease   Scoping review  

摘要： Objective: Delivering a life changing diagnosis can be a distressing experience for patients and a challenging task for professionals. Diagnosis delivery can be especially difficult for individuals with neurodegenerative diseases such as motor neurone disease (MND), multiple sclerosis (MS) and Parkinson's disease (PD). This review aims to scope the literature on doctors' and patients' perspectives on diagnosis delivery for these conditions in order to enhance our understanding in this area and identify potential research gaps. Methods: A scoping review methodology was used, and data were summarised using content analysis. Results: 47 studies fulfilled the inclusion criteria. Studies showed that although patients were generally satisfied with diagnosis delivery, a considerable proportion was still dissatisfied with aspects of the consultation, especially the information and time provided and the doctor's approach. Only six studies addressed doctors' perspectives, which focused more on doctors' practice. Conclusion: There was a significant research gap in professionals' perspectives. The review also found that although basic standards of good practice were being met, a significant proportion of patients were dissatisfied with diagnosis communication. Practice implications: Professionals delivering such diagnoses need to assess and respond to patients' information needs, provide time for questions and maintain an empathic attitude. (C) 2020 Elsevier B.V. All rights reserved.

关键词： Paediatric neurology   Training   Organization   Curriculum   EPNS European Paediatric Neurology syllabus   Specialty  

摘要： Background: Paediatric Neurology (PN) is a discipline focused on diagnosis, comprehensive management and research into diseases of the central and peripheral nervous system from fetal life to transition into adulthood. The European Paediatric Neurology Society first designed and published the European PN training programme in the European Paediatric Neurology Syllabus in 2002. This was important in gaining recognition for the sub-specialty from the European Academy of Paediatrics and the European Academy of Neurology and in 2003 PN was recognized as a sub-specialty of paediatrics and neurology by the Board of the European Union of Medical Specialties. In 2004, the EPNS founded the Committee of National Advisors (CNA) that comprised representatives from national Paediatric Neurology societies, in order to further enhance Europe wide standards in training and practice., The EPNS Training Advisory Board (TAB) offers nation specific advice/support to PN societies on developing training and care systems. In 2019, the 2nd revision of the Paediatric Neurology Syllabus was approved by the EPNS Board and CNA. We aim to give an overview of the training of Paediatric Neurology (PN) specialists (i.e. Paediatric Neurologists), the relevant professional bodies and the current practice of Paediatric Neurology in Europe, as defined geographically by the World Health Organization. Methods: A structured online data collection form was completed by CNA representatives from European countries. The data included training routes and structure of training, epidemiological data, nature of professional societies, organization of Paediatric Neurology care, research, academic life and recognition of the specialty. Results: Data was collected from 43 European countries of which 38 have a national PN Society. In 10 (6 European Union (EU) and 4 non-EU countries) PN is recognized as a core specialty. In 26 countries PN is recognized as a sub-specialty of Paediatrics, Neurology or both (15 EU-11 n

关键词： Insight   Neurological disease   Mood disorder   Cognitive profile  

摘要： Purpose: Many studies have evaluated the characteristics of insight, especially in psychiatric patient populations. However, this construct has been poorly examined within neurological disorders. We explored the relationship between altered insight, mood disorders and neurocognitive functioning in a sample of patients admitted to a neurological rehabilitation unit. Method: Each patient, at the time of hospitalization (T0), underwent an evaluation of the overall cognitive profile, of the frontal functions, and the compilation of scales aimed at investigating the 4 domains under examination of insight and anxiety-depressive symptomatology. After 3 months (T1), at the end of the rehabilitative and supportive treatment, the patients underwent the same evaluation performed at T0. Results: Our results showed significant differences between T0 and T1 in the variables examined related to insight. In particular, there was a correlation between the global cognitive profile, including executive functions, and all insight domains. This confirms how the degree of cognitive deficit, especially of executive type, affects all levels of awareness of the individual. We have also found correlations between mood disorders and insight. In particular, our results show that depression versus anxiety plays a fundamental role in a person's awareness. Conclusions: The study of insight is fundamental not only for the relapses it could have on the patient, but also on those to health care professionals. In fact, having an adequate insight could lead to a greater motivation of the patient to be more complimentary to pharmacological and rehabilitative therapies, also favoring social reintegration. (C) 2020 Elsevier Ltd. All rights reserved.