关键词： chemogenetic tool   epilepsy   L-glutamate-gated chloride channel   ivermectin   novel therapy  

摘要： The conventional paradigm for developing new treatments for disease mainly involves either the discovery of new drug targets, or finding new, improved drugs for old targets. However, an ion channel found only in invertebrates offers the potential of a completely new paradigm in which an established drug target can be re-engineered to serve as a new candidate therapeutic agent. The L-glutamate-gated chloride channels (GluCls) of invertebrates are absent from vertebrate genomes, offering the opportunity to introduce this exogenous, inhibitory, L-glutamate receptor into vertebrate neuronal circuits either as a tool with which to study neural networks, or a candidate therapy. Epileptic seizures can involve L-glutamate-induced hyper-excitation and toxicity. Variant GluCls, with their inhibitory responses to L-glutamate, when engineered into human neurons, might counter the excitotoxic effects of excess L-glutamate. In reviewing recent studies on model organisms, it appears that this approach might offer a new paradigm for the development of candidate therapeutics for epilepsy.

摘要： Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia.

摘要： Mandarin translations of this letter to the editor are available in the online issue.

摘要： Aim To evaluate the associations between motor development in infancy and developmental outcomes at school age. Method Participants were 195 children (99 males, 96 females;mean age [SD] 9y 3mo [3mo], range 8y 4mo-10y 11mo) born to couples whose reduced fertility was or was not treated with assisted reproductive technologies. Motor behaviour was assessed at 4, 10, and 18 months with the Infant Motor Profile (IMP). IQ, neurological optimality score (NOS), and behavioural problem scores were measured at 9 years with the Wechsler Abbreviated Scale of Intelligence, minor neurological dysfunction assessment, and the Child Behavior Checklist respectively. Results Children with a slow developmental trajectory in the IMP-domain adaptability had an IQ 12.6 points lower (95% confidence interval [CI] 4.7-20.4) and an NOS 3.4 points lower (95% CI 0.7-6.2) at 9 years of age than children with typical adaptability development. Children with a slow developmental trajectory in the IMP-domain performance had an IQ 5.0 points lower (95% CI 0.7-9.3) than children with typical performance development. A non-optimal trajectory in IMP-variation and a fluctuating trajectory in IMP-fluency were associated with higher internalizing scores of 3.6 and 5.8 points respectively, than infants with optimal IMP-domain trajectories. Interpretation In relatively low-risk children, motor behaviour in infancy was associated with neurological, cognitive, and behavioural function at school age.

关键词： neck pain   back pain   human constitution   types of higher nervous activity   temperament   ongoing electroencephalogram   spectral composition  

摘要： Forty-seven patients suffering from neck and/or back pain were examined;their temperament was evaluated using the Eysenck Personality Questionnaire (EPQ);the pain syndromes in these subjects were described according to the visual analogous scale (VAS). All patients were subjected to the detailed EEG examination. As was found, characteristics of pain in subjects of the examined group noticeably depended on the type of their temperament. Simultaneously, spectral powers (SPs) of EEG oscillations of the beta range also demonstrated specific dependences on the temperament type. Spectral powers of beta activity showed negative correlations (in many cases significant) with the extra/introversion estimates of the patients, while correlations with the neuroticism level were positive. The mean pain intensity in patients with choleric and melancholic temperaments showed positive correlations with the intensity of beta activity, while correlations of the periodicity of spinal pain with the above activity were positive and stronger. The above differences are assumed to depend on the functional state of the brain and, primarily, on the degree of activation of the ascending reticular formation reflected on the type of temperament of the individual. The importance of the human neuroconstitution for peculiarities of the pathogenesis of reflex neurological disorders of the spine with neck and back pain is discussed.

关键词： Acquired inflammatory demyelinating syndrome   Myelin oligodendrocyte glycoprotein   Autoantibodies   Biomarker   Children   Cell-based assay  

摘要： The differential diagnosis between acquired inflammatory demyelinating syndromes of the central nervous system (CNS), such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and acute disseminated encephalomyelitis (ADEM) can be very challenging at onset. Apart from cerebrospinal fluid oligoclonal bands and anti-aquaporin-4 antibodies (AQP4-Ab), definite diagnostic biomarkers are lacking. Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) have been increasingly described in children with AQP4-seronegative NMOSD, ADEM and other inflammatory demyelinating CND syndromes;despite partial overlaps with AQP4-Ab disease, a novel "MOG-Ab-disorder" phenotype has been suggested. In this study, we tested the presence of MOG-Ab and AQP4-Ab in 57 children at first onset of acute neurological symptoms;three clinical subgroups were identified: 12 patients had acquired inflammatory demyelinating CNS syndromes, 11 had other autoimmune/immune-mediated disorders of the central and peripheral nervous system and 34 had non-immune-mediated CNS disorders. MOG-Abs were found positive only in a subset of cases in the subgroup with acquired inflammatory demyelinating CNS syndromes (in 2/12 patients, both with non-MS phenotype) and in none of the patients with other autoimmune and immune-mediated disorders of the central and peripheral nervous system or with non-immune-mediated disorders of the CNS. Data from the literature review support clinical and analytical observations.

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关键词： Licoricidin   Traumatic brain injury   Oxidative stress   Apoptosis   FoxO3   Wnt   beta-catenin pathway  

摘要： Traumatic brain injury (TBI) is a major cause of death and disability around the world with no effective treatments currently. The present study was aimed to investigate the neuroprotective effect of licoricidin, one of the major components of licorice extract, on TBI mice and further explore the underlying mechanism. Male C57BL/6 mice were modeled by a modified weight-drop method to mimic TBI. All animals received treatment 30 min after TBI. The modified Neurological Severity Score (NSS) tests were performed at 2 h and 1-3 days after TBI. The brain edema was analyzed by dry-wet weight method. The malonaldehyde (MDA) levels and the activities of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) were determined by Elisa. Apoptotic neurons were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunofluorescence and the expression of apoptotic proteins were measured by western blot. Activation of the FoxO3/Wnt/beta-catenin was evaluated by western blot. The results showed that treatment with licoricidin could significantly decline the NSS scores and reduce the brain edema, hence promote the recovery of neurological function in TBI mice. It also elevated the phosphorylation of p66(shc), brought down the levels of MDA, as well as antagonized the decrement in activities of GSH-PX, SOD and CAT induced by TBI. Moreover, licoricidin decreased the TUNEL positive neurons, downregulated the expression of Cyt-C, cleaved-Caspase-3, cleaved-Caspase-9 and Bax and upregulated the Bcl-2, attenuated cellular apoptosis. Licoricidin decreased the expression of FoxO3 and increased the Wnt/beta-catenin in TBI mice. In conclusion, Licoricidin exerted neuroprotective effect on TBI model and the effect was possibly due to its antioxidative effect and antiapoptotic effect via regulating the FoxO3/Wnt/beta-catenin pathway. Licoricidin may be a candidate drug for TBI therapy.

关键词： COVID-19   Alzheimer's dementia   Chronic lung disease   Coronavirus  

摘要： Introduction In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. Methods In this retrospective cohort study, we included 103 adult inpatients (aged >= 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. Results In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer's dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%;specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. Conclusions Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.

关键词： Syndromic craniosynostosis   Neurology   Cerebellar tonsillar herniation   Syringomyelia  

摘要： Background: Children with syndromic craniosynostosis (sCS) have a higher incidence of cerebellar tonsillar herniation (TH) than the general population. In the general population, TH >= 5 mm below the foramen magnum is associated with typical neurological deficits but, in sCS, we do not know whether this degree of TH is required before such deficits occur. Objective: This prospective cohort study aimed to determine the association between findings on neurological assessment and cerebellar tonsillar position. Methods: Magnetic resonance imaging ( MRI) was used to determine TH >= 5 mm and the presence of syringomyelia. In regard to the outcome of neurological deficits, these were categorized according to: A, cerebellar function;B, cranial nerve abnormalities;and C, sensory or motor dysfunction. Results: Twenty of 63 patients with sCS (32% [95% confidence interval 21-45%]) had TH >= 5 mm and/or syringomyelia. There was no significant difference in proportion between individual forms of sCS: 16/34 Crouzon, 2/11 Muenke, 2/12 Apert, and 0/7 Saethre-Chotzen patients. Neurological deficits were prevalent (73% [95% confidence interval 60-83%]), and as frequent in patients with TH >= 5 mm and/or syringomyelia as those without. Surgery occurred in 3 patients overall, and only in Crouzon patients. Conclusion: Determining the effect of TH >= 5 mm on neurologic functioning in sCS patients is used to better determine when surgical intervention is warranted. However, we have found that neurological deficits are prevalent in sCS patients, irrespective of cerebellar tonsillar position, suggesting that such findings are developmental and, in part, syndrome-specific central nervous system features. (c) 2020 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.