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

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.

关键词： SARS-CoV2 infection   COVID-19   Neurological symptoms   Central nervous system   Sex   Neurology   Sleep impairment   Hyposmia   Dysgeusia   Daytime sleepiness  

摘要： Objective: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection. Methods: We included patients hospitalized at the University Hospital of Rome "Tor Vergata", medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer. Results: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression. Conclusions: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms are present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.

关键词： duration   education   Europe   examination   neurology   research fellows   residency training programme   residents   rotations  

摘要： Background and purpose Neurology is rapidly evolving as a result of continuous diagnostic and therapeutic progress, which influences the daily work of neurologists. Therefore, updating residency training programmes is crucial for the future of neurology. Several countries are currently discussing and/or modifying the structure of their neurology residency training programme. A detailed and up-to-date overview of the available European residency training programmes will aid this process. Methods A questionnaire addressing numerous aspects of residency training programmes in neurology was distributed among 38 national representatives of the Resident and Research Fellow Section of the European Academy of Neurology. Results We obtained data from 32 European countries (response rate 84%). The median (range) duration of the residency training programmes was 60 (12-72) months. In the majority of countries, rotations to other medical disciplines were mandatory, mostly psychiatry (69%), internal medicine (66%) and neurosurgery (59%). However, the choice of medical fields and the duration of rotations varied substantially between countries. In 50% of countries, there were formal regulations regarding training in evidence-based medicine, teaching skills and/or leadership qualities. In many countries (75%), residents had to take an examination. Conclusions We found substantial variation among European countries in the duration of residency training programmes, and especially in the choice of obligatory rotations to external medical disciplines. Despite a presumably similar spectrum of patients, neurology residency training programmes across Europe are not harmonized. The structure of the programme should be determined by its relevance for neurologists today and in the future.

关键词： Coronavirus disease 2019   COVID-19   SARS-CoV-2   Neurologic symptoms   Neurological manifestations  

摘要： Background COVID-19 is a virus pandemic. According to the first obtained data, COVID-19 has defined with findings such as cough, fever, diarrhea, and fatigue although neurological symptoms of patients with COVID-19 have not been investigated in detail. This study aims to investigate the neurological findings via obtained face-to-face anamnesis and detailed neurological examination in patients with COVID-19. Methods Two hundred thirty-nine consecutive inpatients with COVID-19, supported with laboratory tests, were evaluated. Detailed neurological examinations and evaluations of all patients were performed. All evaluations and examinations were performed by two neurologists who have at least five-year experience. Results This study was carried out 239 patients (133 male + 106 female) with diagnosed COVID-19. Neurological findings were present in 83 of 239 patients (34.7%). The most common neurological finding was a headache (27.6%). D-dimer blood levels were detected to be significantly higher in patients with at least one neurological symptom than patients without the neurological symptom (p < 0.05). IL-6 level was found to be significantly higher in patients with headache than without headache (p < 0.05). Creatine kinase (CK) level was detected to be significantly higher in patients with muscle pain (p < 0.05). Conclusion Neurological symptoms are often seen in patients with COVID-19. Headache was the most common seen neurological symptom in this disease. Dizziness, impaired consciousness, smell and gustation impairments, cerebrovascular disorders, epileptic seizures, and myalgia were detected as other findings apart from the headache. It is suggested that determining these neurological symptoms prevents the diagnosis delay and helps to prohibit virus spread.

关键词： chronic infantile neurological cutaneous and articular syndrome   etanercept   interleukin-1   NLRP3   tumor necrosis factor-alpha  

摘要： Chronic infantile neurological, cutaneous and articular (CINCA) syndrome is a rare autoinflammatory disease caused by monogenic defects in the NLRP3 gene. Pro-inflammatory cytokines such as interleukin (IL)-1 beta play a crucial role in the pathogenesis, and IL-1 receptor antagonists have been regarded as the mainstay therapy. Endogenous tumor necrosis factor (TNF)-alpha was found recently to be involved in the onset of the disease. Here, we report two Chinese children with CINCA syndrome who had elevated serum levels of TNF-alpha, with one carrying a novel mutation of c.1330T/G (p.444Phe/Val) in exon 3 of the NLRP3 gene. Anti-TNF-alpha (etanercept) therapy successfully alleviated both clinical symptoms and systemic inflammation after 6 months. These results suggest the complexity of the mechanisms of the disease and that TNF-alpha blockade will broaden the therapeutic approach for a subset of patients.

关键词： Cardiac arrest   Cerebral ischemia   Statin  

摘要： BackgroundGlobal ischemia due to cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) causes significant neuronal damage in vulnerable areas in the brain. Currently, a majority of patients eventually die after successful CPR due to neurological injury. Statins have pleiotropic effects including anti-inflammatory and/or antioxidant responses. These pleiotropic effects can have a beneficial role in the post-CPR phase. We tested whether two different types of statins, hydrophilic pravastatin and lipophilic simvastatin, attenuated neurological injury following CA/CPR. The efficacy of pravastatin and simvastatin combination treatment was also ***-anesthetized adult male wild-type C57Bl/6 mice subjected to 8-min CA/CPR were randomized into four groups: control, 2 mg/kg pravastatin, 20 mg/kg simvastatin, or a combination of 3 mg/kg pravastatin and 10 mg/kg simvastatin. Neurobehavioral assessment and histological analyses were performed to assess overall general health condition and neuronal injury, *** treatment with pravastatin and simvastatin significantly reduced neuronal injury in the striatum and hippocampus, reduced cerebral edema, and improved general health at 4 days after CA/CPR. Combination statin treatment upregulated endothelial nitric oxide synthase mRNA in the brain. Pravastatin alone, but not simvastatin alone, improved general health after CA/CPR. Pravastatin was less potent than simvastatin at reducing neuronal injury in the *** treatment with two different types of statins at the correct dose may be a promising approach to neuroprotection following CA/CPR.

关键词： disease management   Europe   movement disorders   rare diseases   survey  

摘要： Background and purpose The diagnosis of rare movement disorders is difficult and specific management programmes are not well defined. Thus, in order to capture and assess care needs, the European Reference Network for Rare Neurological Diseases has performed an explorative care need survey across all European Union (EU) countries. Methods This is a multicentre, cross-sectional study. A survey about the management of different rare movement disorders (group 1, dystonia, paroxysmal dyskinesia and neurodegeneration with brain iron accumulation;group 2, ataxias and hereditary spastic paraparesis;group 3, atypical parkinsonism;group 4, choreas) was sent to an expert in each group of disorders from each EU country. Results Some EU countries claimed for an increase of teaching courses. Genetic testing was not readily available in a significant number of countries. Regarding management, patients' accessibility to tertiary hospitals, to experts and to multidisciplinary teams was unequal between countries and groups of diseases. The availability of therapeutic options, such as botulinum toxin or more invasive treatments like deep brain stimulation, was limited in some countries. Conclusions The management of these conditions in EU countries is unequal. The survey provides evidence that a European care-focused network that is able to address the unmet rare neurological disease care needs and inequalities is highly warranted.