关键词： Encephalitis   Meningitis   Children   Pathogen   NGS  

关键词： gut-brain axis   microflora   microbiome   neurological disorders   precision medicine   computational metagenomics  

摘要： Almost 2500 years after Hippocrates' observations on health and its direct association to the gastrointestinal tract, a paradigm shift has recently occurred, making the gut and its symbionts (bacteria, fungi, archaea and viruses) a point of convergence for studies. It is nowadays well established that the gut microflora's compositional diversity regulates via its genes (the microbiome) the host's health and provides preliminary insights into disease progression and regulation. The microbiome's involvement is evident in immunological and physiological studies that link changes in its biodiversity to its contributions to the host's phenotype but also in neurological investigations, substantiating the aptly named gut-brain axis. The definitive mechanisms of this last bidirectional interaction will be our main focus because it presents researchers with a new conundrum. In this review, we prospect current literature for computational analysis methodologies that accommodate the need for better understanding of the microbiome-gut-brain interactions and neurological disorder onset and progression, through cross-disciplinary systems biology applications. We will present bioinformatics tools used in exploring these synergies that help build and interpret microbial 16S ribosomal RNA data sets, produced by shotgun and high-throughput sequencing of healthy and neurological disorder samples stored in biological databases. These approaches provide alternative means for researchers to form hypotheses to their inquests faster, cheaper and swith precision. The goal of these studies relies on the integration of combined metagenomics and metabolomics assessments. An accurate characterization of the microbiome and its functionality can support new diagnostic, prognostic and therapeutic strategies for neurological disorders, customized for each individual host.

关键词： Instrumental timed up and go test   Rehabilitation   Responsiveness   Elderly   ITUG   Balance and locomotor impairment  

摘要： Background: The timed up and go (TUG) test is widely used for assessing treatments effectiveness on elderly mobility. Although the TUG test consists of different tasks (e.g. walking and turning), the total TUG duration (TTD) is usually the only outcome measure, with TTD shortening indicating the patient's improvement. Research question: Does TTD shortening reflect the improvement of each TUG tasks or does it reflect the improvement of only some of them? Methods: This retrospective study recruited 120 elderly patients (mean, SD: 76.9, 6.6 years) admitted to inpatient rehabilitation because of an acute or chronic neurological disease (acute patients, AP;chronic patients, CP). TTD and TUG tasks duration was measured on admission and discharge (five trials/session) by means of the instrumental TUG test (ITUG). Likelihood ratios (LRs) were used for inferring TUG tasks improvement from TTD improvement. TTD and TUG tasks have improved if at least four measurements on discharge were shorter than the shortest measurement on admission. Results: TTD improvement per se is not enough to claim that all the TUG tasks have improved (LRAP+ = 1.32;LRCP+ = 1.85). Conversely, if TTD has not improved, not even a single TUG task has improved (LRAP- = 0.13;LRCP- = 0.19). If TTD has improved, there is at least one TUG task that actually improved (L-AP(+) = 3.17;L-CP(+) = 9.54). The improvement of all TUG tasks can be only inferred in the (unusual) event of a large TTD shortening (AP: > 39%, L-AP(+) = 6.26;CP: > 30%, L-CP(+) = 9.0). Significance: In most cases, TTD improvement is not associated with the improvement of all TUG tasks. Moreover, when TTD has improved there is at least a TUG task that has improved, but that remains unknown. To actually understand how treatments ameliorate patients' mobility, ITUG with TUG task duration measurement should be preferred to TTD.

关键词： Phthalate   Endocrine disruptor   Kynurenine Pathway (KP)   Quinolinic acid (QA)   Crossover study   Men  

摘要： Background: Quinolinic acid (QA), a neuroactive metabolite of the Kynurenine Pathway (KP), is an excitotoxin that is implicated in the pathogenesis of many neurological disorders. KP is the main tryptophan degradation pathway. Phthalates can structurally mimic tryptophan metabolites and diets containing phthalates in rats enhanced the production and excretion of QA. However, there are no human studies that have examined the association between phthalates and QA. Objectives: Taking advantage of different mesalamine formulations with/without dibutyl phthalate (DBP), we assessed whether DBP from mesalamine (> 1000x background) altered the urinary concentrations of QA. Methods: Men with inflammatory bowel disease participated in a prospective crossover pilot study. 15 Men were on non-DBP mesalamine (background) at baseline crossed-over for 4 months to high-DBP mesalamine (high) (B1H-Arm) and vice versa for 15 men who were on high-DBP mesalamine at baseline (H1B-Arm). Men provided 60 urine samples (2/man). We estimated crossover and cross-sectional changes in the creatinine normalized-QA using multivariable linear mixed effect models with random intercepts. Results: At baseline, men who were on high-DBP mesalamine (H1B-Arm) had 72%, (95% confidence interval (CI): 18, 151) higher normalized-QA than men who were on background exposure and when high-DBP mesalamine was removed for four months, normalized-QA decreased with 32%, (95% CI: -45.0, -15.1). Consistently, when men in B1H-Arm were newly-exposed to high-DBP mesalamine, normalized-QA increased with 11%, (95% CI: -11, 38). Conclusions: High-DBP exposure from mesalamine increased the urinary concentrations of QA, which was largely reversed after removal of the high-DBP exposure for four months. This novel hypothesis should warrant new promising research considering the KP and QA concentrations as a plausible mediator for the neurotoxicity possibly linked with phthalate exposures.

关键词： Infective endocarditis   Mycotic aneurysm   Neurological complications   Stroke   Cardiac surgery   Thrombectomy  

摘要： Purpose of ReviewThe purpose of this narrative review and update is to summarize the current knowledge and provide recent advances on the neurologic complications of infective *** FindingsNeurological complications occur in about one-fourth of patients with infective endocarditis. Brain MRI represents a major tool for the identification of asymptomatic lesions, which occur in most of the patients with infective endocarditis. The usefulness of systematic brain imaging and the preferred treatment of patients with infective endocarditis and silent brain lesions remains uncertain. The basis of treatment of infective endocarditis is early antimicrobial therapy. In stroke due to infective endocarditis, anticoagulation and thrombolysis should be avoided. Endovascular treatment can be useful for both acute septic emboli and mycotic aneurysms, but evidence is still limited. In patients with neurological complications, cardiac surgery can be safely performed early, if *** optimal management of a patients with neurological complications of infective endocarditis needs an individualized case discussion and the participation of a multidisciplinary team including neurologists, cardiologists, cardiothoracic surgeons, neuroradiologists, neurosurgeons, and infectious disease specialists.

关键词： Deep sequencing   Neurological disorders   mitDNA   Causative mutation   9017C   9010A  

摘要： Mitochondrial diseases (MD) are a group of diseases that can be caused by either mutations in the mitochondrial genome or nuclear DNA. MD may be difficult to diagnose since very often they are highly heterogeneous and with overlapping phenotypes. Molecular genomics approaches, especially NGS have helped in this sense. In this study we have sequenced the mitochondrial genome of a girl with an unspecific neurological disorder and her mother. The later, while neurologically unaffected, suffers from a myopathy without clear cause. We were able to detect two non-synonymous mutations in the MT-ATP6 gene, which we propose are strong candidates for causative agents. 9017C as the main candidate present at high heteroplasmy frequency in the patient (83,2%) and moderate in the mother (45,4%) while it has a low frequency in the general population. It might act alone or in conjunction with 9010A as an accessory mutation. Evolutionary analysis showed that both mutations were located in a critical position in the F-0 a subunit, from F-0-F-1 ATPase. Functional studies showed that carriers of those mutations in comparison to an unaffected individual (father) presented a decrease in the basal and ATP dependent oxygen consumption rate and a decrease in the maximum respiration rate.

摘要： The article presents a case study of a 32-yr-old seaman, who was hospitalized due to fever associated with headache, hallucinations, back pain, and multiple bruises at a Southeast Asia tertiary hospital. It discussed his treatment with antipyretics and oral ciprofloxacin for jaundiced and delirious and diagnosed with inpatient rehabilitation in which included articulatory exercises, strengthening exercises, gait retraining and balance training.

关键词： Disease genetics   Neurodegenerative diseases   Pathogenesis   RNA metabolism  

摘要： Biomolecular condensation arising through phase transitions has emerged as an essential organizational strategy that governs many aspects of cell biology. In particular, the role of phase transitions in the assembly of large, complex ribonucleoprotein (RNP) granules has become appreciated as an important regulator of RNA metabolism. In parallel, genetic, histopathological and cell and molecular studies have provided evidence that disturbance of phase transitions is an important driver of neurological diseases, notably amyotrophic lateral sclerosis (ALS), but most likely also other diseases. Indeed, our growing knowledge of the biophysics underlying biological phase transitions suggests that this process offers a unifying mechanism to explain the numerous and diverse disturbances in RNA metabolism that have been observed in ALS and some related diseases-specifically, that these diseases are driven by disturbances in the material properties of RNP granules. Here, we review the evidence for this hypothesis, emphasizing the reciprocal roles in which disease-related protein and disease-related RNA can lead to disturbances in the material properties of RNP granules and consequent pathogenesis. Additionally, we review evidence that implicates aberrant phase transitions as a contributing factor to a larger set of neurodegenerative diseases, including frontotemporal dementia, certain repeat expansion diseases and Alzheimer disease.

关键词： Anticholinergics   Antipsychotics   Clinical audit  

摘要： Antiparkinson medications are recommended as a second-line treatment of the adverse effects of antipsychotic drugs. They are often associated with anticholinergic side effects that can negatively influence observance. In an evaluation of professional practices (EPP), a targeted clinical audit was performed with the theme the prescription of anticholinergic treatments in the management of neurological adverse effects associated with antipsychotic drugs. A retrospective audit of the clinical files of hospitalized patients treated with anticholinergics was performed using HAS (Haute Autorite de sante) methodology. Seven evaluation criteria were defined based on existing references. An analysis of the conformity of these criteria suggested three areas of improvement: decrease in the number of anticholinergic prescriptions, optimizing systematic prescriptions, reducing the delay to prescription reevaluation. Actions were taken to communicate with prescribers via a group EPP and pharmaceutical interventions. A second audit was performed to evaluate the changes in professional practices. A decrease in the number of anticholinergic prescriptions was observed from 226 to 174. Anticholinergics were prescribed with a greater number of antipsychotics during the second audit and with higher doses of antipsychotics. In case of association with antipsychotic monotherapy, the proportion of neuroleptics increased from 9% to 13% while with atypical antipsychotics (with fewer adverse effects) it decreased from 19% to 15%. The delay to the re-evaluation of treatments decreased. On the other hand, one third of the prescriptions in full hospitalizations were not re-evaluated every trimester (up to 85 months of delay). This study made it possible to decrease the number of anticholinergic prescriptions. The use of anticholinergics is in conformity with guidelines (situations with a risk of adverse effects). On the other hand, the proportion of anticholinergics is above the expected rate (2

关键词： Medical College of Wisconsin   Neurosurgery history   Spine fellowship  

摘要： The Medical College of Wisconsin Department of Neurosurgery delivers subspecialty adult and pediatric neurosurgical care that is patient-centered, evidence-informed, and value-based. Medical College of Wisconsin research advances the science of neurological disease with the goal of a positive translational effect on clinical care. The department supports an environment of education and scholarship for trainees, faculty, and staff alike. The journey to become a neurosurgical center of excellence was accomplished with the leadership and foresight of the men and women who turned their dreams into reality. The establishment and rise of the department as a national force for neurosurgery and spine is an elegant example of the combination of individual leadership and foresight with synergistic institutional support.