关键词： brachycephalic   butterfly vertebra   hemivertebra   screw-tail   spina bifida   transitional vertebra  

摘要： Congenital vertebral malformations are common findings on diagnostic imaging of the vertebral column in "screw-tailed" brachycephalic dogs. The aims of this study were to evaluate the prevalence and anatomical characteristics of lumbosacral congenital vertebral malformations in French Bulldogs, English Bulldogs, and Pugs presenting for problems unrelated to spinal disease, as well as possible associations with the degree of tail malformation, lumbosacral intervertebral disc herniation, or spondylosis deformans. In this retrospective cross-sectional study, CT scans of vertebrae L6 to S3 and of the coccygeal vertebrae were reviewed for type of congenital vertebral malformations (hemivertebrae, block vertebrae, lumbosacral transitional vertebrae, and spina bifida), lumbosacral intervertebral disc herniation, lumbosacral spondylosis deformans, and degree of tail malformation. In 76 (51.0%) of the 149 included dogs (53 French Bulldogs, 37 English Bulldogs, and 59 Pugs) at least one type of congenital vertebral malformations was found, with lumbosacral transitional vertebrae being the most common (34.2%). There was a significantly higher prevalence of lumbosacral transitional vertebrae (54.2%) and lower prevalence of hemivertebrae (1.7%) in Pugs compared to English (13.5% and 24.3%, respectively) and French Bulldogs (26.4% and 32.0%, respectively). Tail malformation was significantly more severe in dogs with evidence of hemivertebrae. Congenital vertebral malformations are a common finding in the lumbosacral vertebral column of French Bulldogs, English Bulldogs, and Pugs. These anatomical variances need to be considered when interpreting diagnostic studies and when planning for neurosurgical and neurodiagnostic procedures. Furthermore, this study suggests a possible association between the degree of tail malformation and lumbosacral hemivertebrae.

关键词： Preclinical safety studies   Toxicology   Dog electroencephalogram   Telemetry   Seizures   Convulsions   Premonitory signs   Non-human primates   Species sensitivity  

摘要： Introduction: Convulsions in toxicology studies can be the first indication of seizure liability. Drug levels during convulsions are not usually evaluated. This, and exposure variability after oral administration, complicates estimation of safety margins. The electroencephalogram (EEG) enables symptoms to be attributed to seizures and to collect samples during epileptiform activity without clinical convulsion. We evaluated an EEG-study design for optimized detection of neurological symptoms. Additionally, we assessed whether EEG-based anticonvulsive treatment is feasible, to prevent progression to convulsions and if dogs have higher sensitivity towards neurological symptoms than non-human-primates. Methods: Three compounds that previously were tested in non-human-primates were selected to evaluate the dog EEG-study design. Two substances were administered in escalating intravenous doses;the third was given as single oral dose. Per compound, one male and one female telemetered dog were evaluated;males also had cerebrospinal-fluid-ports. Drug levels, video-EEG and clinical symptoms were evaluated and compared to previous studies. Results: While similar neurological symptoms were induced, intravenous administration reduced experimental time compared to standard toxicology studies. EEG analysis could link animal behavior to seizures but did not allow convulsion prevention. This was due to artefacts and the short latency between onset of epileptiform EEG activity and clinical convulsions. Free plasma concentrations during convulsions were comparable between dogs and non-human-primates. Discussion: The findings suggest that infusion studies provide a possibility to investigate neurological adverse effects in few animals in a short time period. For candidates with a high risk for seizures, such studies can guide dose selection for longer regulatory studies and improve safety margin definition.

关键词： asthenia   brain   diagnosis   ethics   limb   nervous system disorders   neuroscience  

摘要： This scientific commentary refers to The prognosis of functional limb weakness: a 14-year case-control study', by Gelauff et al. (doi:).

关键词： Tuberous sclerosis   NitroSynapsin   Extrasynaptic NMDA receptor   E/I imbalance   Hippocampal long-term potentiation  

摘要： Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by heterozygous mutations in the TSC1 or TSC2 gene. TSC is often associated with neurological, cognitive, and behavioral deficits. TSC patients also express co-morbidity with anxiety and mood disorders. The mechanism of pathogenesis in TSC is not entirely clear, but TSC-related neurological symptoms are accompanied by excessive glutamatergic activity and altered synaptic spine structures. To address whether extrasynaptic (e)NMDA-type glutamate receptor (NMDAR) antagonists, as opposed to antagonists that block physiological phasic synaptic activity, can ameliorate the synaptic and behavioral features of this disease, we utilized the Tsc2(+/-) mouse model of TSC to measure biochemical, electrophysiological, histological, and behavioral parameters in the mice. We found that antagonists that preferentially block tonic activity as found at eNMDARs, particularly the newer drug NitroSynapsin, provide biological and statistically significant improvement in Tsc2(+/-) phenotypes. Accompanying this improvement was correction of activity in the p38 MAPK-TSC-Rheb-mTORC1-S6K1 pathway. Deficits in hippocampal long-term potentiation (LTP), histological loss of synapses, and behavioral fear conditioning in Tsc2(+/-) mice were all improved after treatment with NitroSynapsin. Taken together, these results suggest that amelioration of excessive excitation, by limiting aberrant eNMDAR activity, may represent a novel treatment approach for TSC.

摘要： Treatment options for multiple sclerosis (MS) have improved in the past 20 years, with new oral disease modifying drugs and monoclonal antibodies becoming available. The success seen with these drugs in MS, and their various mechanisms of action, has led to them being investigated in other neurological and psychiatric disorders. This review article summarises the ongoing and completed studies of MS drugs in neurological and psychiatric conditions other than MS. The most promising results are for interferon beta in human T cell leukaemia virus 1 associated myelopathy/tropical spastic paraparesis and glioma, and for fingolimod in acute ischaemic stroke and intracerebral haemorrhage. The coming years could see the arrival of exciting new therapies for disorders that neurologists have historically found difficult to treat and that represent a significant unmet clinical need.

关键词： Urinary tract infections   Microbiological phenomena   Anti-bacterial agents   Drug resistance   Bacterial  

摘要： Objectives: Urinary tract infection (UTI) is a common medical complication experienced by patients with neurologic diseases. In this study, we established the microbial etiologies of UTI, and resistances to antibiotics in UTI as well as determining which appropriate empirical antibiotics should be used to treat UTI in neurological patients. Designs and methods: We retrospectively reviewed microbial etiologies and antimicrobial resistance among patients experiencing UTI events in the neurology ward of Seoul National University Hospital from 2007 to 2016. Results: The total number of UTI events observed was 301, and Klebsiella pneumoniae was the most common pathogen observed in UTIs. But in catheter-associated UTI (CAUTI), Enterococcus species were the most prevalent pathogens. Susceptibility to commonly-prescribed antibiotics decreased over 10 years, indicating increased antibiotic resistance in pathogens associated with UTI. ESBL-producing K. pneumoniae increased significantly, while increases of MDR K. pneumoniae, ESBL-producing E. coli, and VRE were not observed. Conclusions: The worldwide trend of increasing drug-resistant pathogens should be considered, and further studies on antibiotics resistance in UTI are needed. These data will greatly assist physicians when they select antibiotics to treat UTIs in neurological patients. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

摘要： Aim To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA;approximately 38-44wks);and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. Method A total of 257 infants (91 very preterm, 166 moderate-late preterm;120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm;131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. Results Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation;NNNS quality of movement with the corona radiata;HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. Interpretation White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm.

关键词： Zika virus   Brain diseases   Human mesenchymal stem cells   Proteome   Microcephaly  

摘要： The recent microcephaly outbreak in Brazil has been associated with Zika virus (ZIKV) infection. The current understanding of damage caused by ZIKV infection is still unclear, since it has been implicated in other neurodegenerative and developmental complications. Here, the differential proteome analysis of human mesenchymal stem cells (hMSC) infected with a Brazilian strain of ZIKV was identified by shotgun proteomics (MudPIT). Our results indicate that ZIKV induces a potential reprogramming of the metabolic machinery in nucleotide metabolism, changes in the energy production via glycolysis and other metabolic pathways, and potentially inhibits autophagy, neurogenesis, and immune response by downregulation of signaling pathways. In addition, proteins previously described in several brain pathologies, such as Alzheimer's disease, autism spectrum disorder, amyotrophic lateral sclerosis, and Parkinson's disease, were found with altered expression due to ZIKV infection in hMSC. This potential link between ZIKV and several neuropathologies beyond microcephaly is being described here for the first time and can be used to guide specific follow-up studies concerning these specific diseases and ZIKV infection.

关键词： Neuropathic pain   Pharmacoresistance   Painful neuropathy   Refractory pain  

摘要： To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1month after titration to the highest tolerable dose. Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.