摘要： Aim To assess reliability and predictive validity of the neurological scale of the Standardized Infant NeuroDevelopmental Assessment (SINDA), a recently developed assessment for infants aged 6 weeks to 12 months. Method To assess reliability, three assessors independently rated video-recorded neurological assessments of 24 infants twice. Item difficulty and discrimination were determined. To evaluate predictive validity, 181 infants (median gestational age 30wks [range 22-41wks];92 males, 89 females) attending a non-academic outpatient clinic were assessed with SINDA's neurological scale (28 dichotomized items). Atypical neurodevelopmental outcome at 24 months or older corrected age implied a Bayley Mental Developmental Index or Psychomotor Developmental Index lower than 70 or a diagnosis of cerebral palsy (CP). Predictive values were calculated from SINDA (2-12mo corrected age, median 3mo) and typical versus atypical outcome. Results Intraclass correlation coefficients of intrarater and interrater agreement of the neurological score varied between 0.923 and 0.965. Item difficulty and discrimination were satisfactory. At 24 months or older, 56 children (31%) had an atypical outcome (29 had CP). Atypical neurological scores (below 25th centile, <= 21) predicted atypical outcome and CP with sensitivities of 89% and 100%, and specificities of 94% and 81% respectively. Interpretation SINDA's neurological scale is reliable and in a non-academic outpatient setting has a satisfactory predictive validity for atypical developmental outcome, including CP, at 24 months or older.

关键词： burns   case report   vehicle safety   seat heater   wound care  

摘要： Background: Car seat heaters are an increasingly common amenity in vehicles in the United States, but they have been shown to place neurologically impaired patients at risk for significant burns. Case Report: We discuss the case of a neurologically intact and otherwise healthy 49-year-old man who presented to the Emergency Department with second-degree gluteal and posterior upper thigh burns after using a car seat warmer for 8 consecutive hours. At no point during the course of his drive did he experience discomfort beyond feeling slightly warm. The patient was treated with supportive therapy and standard wound care, and he had a full recovery after 10 days. We review the pathophysiology of burns and discuss how seat heaters can place even neurologically intact patients at risk for significant burn injuries. Why Should an Emergency Physician Be Aware of This?: Our case is the first published report of a neurologically intact patient sustaining significant burns from the use of a car seat heater. This case illustrates that burn injuries can develop after prolonged exposure even at low temperatures. Emergency physicians should perform a careful skin examination on all patients presenting with gluteal discomfort in whom a history of car seat warmer use is obtained. (C) 2019 Elsevier Inc. All rights reserved.

关键词： Induced pluripotent stem cells   Embryonic stem cells   Drug screening   Drug discovery   High content screening   Neurodegeneration   Parkinson's disease   Alzheimer's disease   Motor neuron disease   Huntington's disease  

摘要： Induced pluripotent stem cells and their derivatives have become an important tool for researching disease mechanisms. It is hoped that they could be used to discover new therapies by providing the most reliable and relevant human in vitro disease models for drug discovery. This review will summarize recent efforts to use stem cell-derived neurons for drug screening. We also explain the current hurdles to using these cells for high-throughput pharmaceutical screening and developments that may help overcome these hurdles. Finally, we critically discuss whether induced pluripotent stem cell-derived neurons will come to fruition as a model that is regularly used to screen for drugs to treat neurological diseases. (C) 2019 Elsevier Inc. All rights reserved.

关键词： apoptosis   caspase-3   hypoxic-ischemic brain damage   LY294002   neonatal rabbit   neurological impairment   neuron   PI3K   Akt signaling pathway  

摘要： ObjectiveHypoxic-ischemic brain damage (HIBD), frequently occurring in infancy and childhood, is a major cause of mortality and severe neurologic impairment. This study was performed to examine the effect of the PI3K/Akt signaling pathway on HIBD in a neonatal rabbit model. Materials and MethodsUterine artery occlusion was used to establish HIBD models in neonatal rabbits, which were then subjected to sham operation, dimethyl sulfoxide (2mL) or LY294002 (inhibitor of PI3K/Akt signaling pathway, 6.4g/kg). Behavioral neurological assessment was performed in neonatal rabbits delivered by cesarean section, after which serum neuron-specific enolase (NSE) level and cerebral water content were determined. The level of cleaved caspase-3 level and apoptosis of neurons were observed by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, the expression of PI3K/Akt signaling pathway- and apoptosis-related factors was examined. ResultsIn neonatal rabbits, HIBD increased the fetal death rate;reduced neurological scores of posture, righting reflex, and deglutition reflex;elevated serum NSE levels, cerebral water content, cleaved caspase-3-positive expression in hippocampal CA1 region and apoptotic neurons;inactivated PI3K/Akt signaling pathway as well as reduced Bcl-2 expression and increased BAD and Bax expression. Notably, the treatment of LY294002 further aggravated neurological impairment in neonatal rabbits in response to HIBD. ConclusionFollowing the HIBD caused by intrauterine asphyxia, the LY294002 administered through auricular vein infusion into pregnant rabbits exacerbates neurological impairment of neonatal rabbits, suggesting that inhibition of PI3K/Akt signaling pathway may serve as a candidate therapeutic target for neurological recovery.

关键词： education   neurology training   quality   subspecialty  

摘要： Background Neurology has increasing subspecialization. Some disorders, such as cerebrovascular diseases, dementia and headache, are highly prevalent in the general population, while others, such as movement disorders and multiple sclerosis, are rarer. Thus, there may be a mismatch between neurologists' interests and the population needs. Aims of the Study To investigate the perceived prestige of neurological disorders among residents in neurology. Methods The study was conducted as a questionnaire survey among residents in neurology in Norway. Results All the 17 neurological departments in Norway participated. In total, 143 residents participated (86% response rate). Mean age was 32.5 years. The respondents had on average 28 months of clinical training in neurology. The subspecialty with the highest prestige was cerebrovascular diseases, scored by 62% as the most prestigious, followed by multiple sclerosis (36%) and epilepsy (7%). The subspecialties with the lowest prestige were headache (2.8%) and dementia (1.4%). None of the tested variables (gender, age, months in clinical training or type of hospital) were associated with the perceived prestige of neurological disorders. Conclusion Cerebrovascular disease was perceived as the most prestigious subspecialty. Headache and dementia, which are major contributors to worldwide disability, have low status among residents in neurology.

摘要： Autophagy is a tightly modulated lysosomal degradation pathway. Genetic disorders of autophagy during nervous system development may lead to developmental delay, neurodegeneration, and other neurological signs in children. Here we aimed to summarize single gene disorders that perturb various steps of autophagy pathway and their roles in the causation of childhood neurological diseases. Numerous childhood-onset disorders are caused by mutations that impact the autophagy pathway. These can manifest with a range of features including ataxia, spastic paraplegia, and intellectual disability. Defective proteins causing such diseases can interfere with autophagy flux at different stages of the itinerary. Defective autophagy may be an important contributor to the pathological features of various childhood neurodegenerative diseases and lead to the accumulation of aberrant protein and dysfunctional organelles. Insights into the relevant cell biological processes may help understand pathophysiological mechanisms and inspire autophagy-restoring therapeutic approaches. What this paper adds

关键词： Muscular dystrophy   Ataxia   MSTO1   Cerebellar atrophy   Progressive cerebellar involvement  

摘要： Recessive mutations in the MSTO1 gene, encoding for a mitochondrial distribution and morphology regulator, have been recently described in a very limited number of patients with multisystem involvement, mostly characterized by myopathy or dystrophy, cerebellar ataxia, pigmentary retinopathy and raised creatine kinase levels. Here we report an additional patient with recessive MSTO/-related muscular dystrophy (MSTO1-RD), and clinical and radiological evidence of progressive cerebellar involvement. Whole-exome sequencing identified two novel MSTO1 missense variants, c.766C > T (p. (Arg256Trp) and c.1435C > T (p. (Pro479Ser), predicted as damaging by in silico tools. We also report a distinct pattern of selective involvement on muscle MRI in MSTO1-RD. This case confirms a consistent MSTOI-related neuromuscular phenotype and in addition suggests a progressive neurological component at least in some patients, in keeping with the mitochondrial role of the defective protein. (C) 2019 Published by Elsevier B.V.