关键词： coronavirus   nervous system   neuroinvasion   pathophysiology  

摘要： The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a significant and urgent threat to global health. This review provided strong support for central nervous system (CNS) infection with SARS-CoV-2 and shed light on the neurological mechanism underlying the lethality of SARS-CoV-2 infection. Among the published data, only 1.28% COVID-19 patients who underwent cerebrospinal fluid (CSF) tests were positive for SARS-CoV-2 in CSF. However, this does not mean the absence of CNS infection in most COVID-19 patients because postmortem studies revealed that some patients with CNS infection showed negative results in CSF tests for SARS-CoV-2. Among 20 neuropathological studies reported so far, SARS-CoV-2 was detected in the brain of 58 cases in nine studies, and three studies have provided sufficient details on the CNS infection in COVID-19 patients. Almost all in vitro and in vivo experiments support the neuroinvasive potential of SARS-CoV-2. In infected animals, SARS-CoV-2 was found within neurons in different brain areas with a wide spectrum of neuropathology, consistent with the reported clinical symptoms in COVID-19 patients. Several lines of evidence indicate that SARS-CoV-2 used the hematopoietic route to enter the CNS. But more evidence supports the trans-neuronal hypothesis. SARS-CoV-2 has been found to invade the brain via the olfactory, gustatory, and trigeminal pathways, especially at the early stage of infection. Severe COVID-19 patients with neurological deficits are at a higher risk of mortality, and only the infected animals showing neurological symptoms became dead, suggesting that neurological involvement may be one cause of death.

关键词： COVID-19   SARS-CoV-2   Oligoclonal bands   CSF Protein   CSF cell count  

摘要： Background: Limited literature exists on Cerebrospinal fluid (CSF) findings in COVID-19 patients with neurological symptoms. In this review, we conducted a descriptive analysis of CSF findings in patients with COVID-19 to understand prognosis and explore therapeutic options. Methods: We searched PubMed, Google Scholar, and Scopus databases using the keywords "SARS-CoV-2 in cerebrospinal fluid" and "SARS-CoV-2 and CNS Complications" for reports of CSF findings in COVID-19 related neurological manifestations. Descriptive analyses were conducted to observe the CSF protein and cell counts based on age, gender, severity, fatality of COVID-19, and whether central (CNS) or peripheral nervous system (PNS) was associated. Results: A total of 113 patients were identified from 67 studies. Of these, 7 patients (6.2%) were fatal COVID-19 cases and 35 patients (31%) were considered severe COVID-19 cases. CSF protein was elevated in 100% (7/7) of the fatal cases with an average of 61.28 mg/dl and in 65.0% (52/80) in non-fatal cases with an average 56.73 mg/dl. CSF protein levels were elevated in 74.5% (38/51) patients with non-severe COVID-19 and 68.6% (24/35) in those with a severe COVID-19 infection. CSF cell count was increased in 43% of fatal cases, 25.7% severe cases, and 29.4% of non-severe cases. Conclusion: Our analysis showed that the most common CSF findings situation in COVID-19 infection is elevated protein with, very occasionally, mild lymphocyte predominant pleocytosis. Further studies to elucidate the pathophysiology of neurological complications in COVID-19 are recommended. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-ncnd/4.0/).

关键词： Axons   Mathematical model   Couplings   Extracellular   Electric potential   Brain modeling   Ephaptic coupling   tract geometry   myelinated nerve fibers   action potential   synchronization  

摘要： The study of axon tracts is important in neurophysiology. In this paper, we study axon tracts with arbitrary geometry and present a governing equation for ephaptic coupling among the constituent axons. We derive this equation and simulate it, obtaining a novel, geometry-dependent, delayed coupling phenomenon. This has relevance for how an axon tract communicates data in a neurological network.

关键词： Primary Sjogren's syndrome   Facial pain   Autonomic neuropathy   Ataxic polyneuropathy   Cranial nerve neuropathy   Carpal tunnel syndrome   Myasthenia gravis   Multiple mononeuropathy   Motor neuron syndrome   Pure motor polyneuropathy   Non-ataxic painful polyneuropathy   Polyradiculoneuropathy   Pure sensory polyneuropathy   Sensorimotor polyneuropathy   Small fiber polyneuropathy   Sural neuropathy   Trigeminal affectation  

摘要： Keywords: Primary Sjogren's syndrome; Facial pain; Autonomic neuropathy; Ataxic polyneuropathy; Cranial nerve neuropathy; Carpal tunnel syndrome; Myasthenia gravis; Multiple mononeuropathy; Motor neuron syndrome; Pure motor polyneuropathy; Non-ataxic painful polyneuropathy; Polyradiculoneuropathy; Pure sensory polyneuropathy; Sensorimotor polyneuropathy; Small fiber polyneuropathy; Sural neuropathy; Trigeminal affectation EN Primary Sjogren's syndrome Facial pain Autonomic neuropathy Ataxic polyneuropathy Cranial nerve neuropathy Carpal tunnel syndrome Myasthenia gravis Multiple mononeuropathy Motor neuron syndrome Pure motor polyneuropathy Non-ataxic painful polyneuropathy Polyradiculoneuropathy Pure sensory polyneuropathy Sensorimotor polyneuropathy Small fiber polyneuropathy Sural neuropathy Trigeminal affectation *** *** 1 02/25/21 20210301 NES 210301 Facial pain is a challenging entity in medicine, and has a wide range of differential diagnoses. Primary Sjogren's syndrome, Facial pain, Autonomic neuropathy, Ataxic polyneuropathy, Cranial nerve neuropathy, Carpal tunnel syndrome, Myasthenia gravis, Multiple mononeuropathy, Motor neuron syndrome, Pure motor polyneuropathy, Non-ataxic painful polyneuropathy, Polyradiculoneuropathy, Pure sensory polyneuropathy, Sensorimotor polyneuropathy, Small fiber polyneuropathy, Sural neuropathy, Trigeminal affectation 95, 19 2016, e3632 10.1097/md.0000000000003632 28 J. Font, J. Valls, R. Cervera, A. Pou, M. Ingelmo, F. Graus, Pure sensory neuropathy in patients with primary Sjogren's syndrome: clinical, immunological, and electromyographic findings. Sjögren's Syndrome: an undiagnosed etiology for facial pain Case series with review of neurological manifestation of Sjögren syndrome. [Extracted from the article]

关键词： CAPE   neurological disorders   pinocembrin   propolis   psychiatric disorders  

摘要： Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well-explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro-inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

关键词： Palliative care   pediatric   patient-centered outcome research   outcome measure   factor analysis   questionnaire design   multicenter study   prospective study  

摘要： Background: Comprehensive outcome measurement in pediatric palliative care focusing on the entire unit of care, that is, the affected child and its family, is crucial to depict treatment effects. Despite its increasing relevance, no appropriate multidimensional outcome measures exist for the largest patient group in this field, namely children with severe neurological impairments. Aim: The aim of this study was to develop and validate a family-centered multidimensional outcome measure for pediatric palliative care patients with severe neurological impairment that encompasses the entire unit of care. Design: Based on results of a qualitative study, the questionnaire was developed by consensus-based generation of questions. It was validated in a multicenter prospective study employing exploratory and confirmatory factor analyses as well as reliability and item analyses. Setting: A total of 11 pediatric palliative care teams across Germany aided in the recruitment of study participants. Questionnaires were answered by 149 parents of children with severe neurological impairment and 157 professional caregivers. Results: The exploratory factor analysis of parent data revealed a 6-factor structure of the questionnaire representing: symptoms, the child's social participation, normalcy, social support, coping with the disease and caregiver's competencies. This structure was verified by a confirmatory factor analysis of professional caregiver data. Five separate items regarding siblings, partners, and further symptoms not applicable for all patients were added to ensure full multidimensionality. Conclusion: A validated outcome tool for severely neurologically impaired pediatric palliative care patients, the FACETS-OF-PPC, now exists. Due to its concise length and appropriate psychometric properties, it is well suited for clinical application.

关键词： Autism spectrum disorders   Gene expression profiling   Gene regulation   Genetics of the nervous system   Molecular neuroscience  

摘要： Boulting et al. profile activity-dependent gene expression and regulatory elements in human induced pluripotent stem cell-derived GABAergic neurons and uncover a possible role for calcium-responsive gene promoters of these neurons in autism risk. Neuronal activity-dependent gene expression is essential for brain development. Although transcriptional and epigenetic effects of neuronal activity have been explored in mice, such an investigation is lacking in humans. Because alterations in GABAergic neuronal circuits are implicated in neurological disorders, we conducted a comprehensive activity-dependent transcriptional and epigenetic profiling of human induced pluripotent stem cell-derived GABAergic neurons similar to those of the early developing striatum. We identified genes whose expression is inducible after membrane depolarization, some of which have specifically evolved in primates and/or are associated with neurological diseases, including schizophrenia and autism spectrum disorder (ASD). We define the genome-wide profile of human neuronal activity-dependent enhancers, promoters and the transcription factors CREB and CRTC1. We found significant heritability enrichment for ASD in the inducible promoters. Our results suggest that sequence variation within activity-inducible promoters of developing human forebrain GABAergic neurons contributes to ASD risk.

关键词： coronavirus disease‐   2019   headache   neurological symptoms   severe acute respiratory syndrome coronavirus 2   trigeminal neuralgia  

摘要： Objective To describe a case report of trigeminal neuralgia (TN) due to coronavirus disease-2019 (COVID-19). Background In March 2020, the World Health Organization declared COVID-19 as a pandemic. Respiratory system manifestations are dominant in this new disease. However, numerous case series and reviews have been published on the neurological manifestations, highlighting the potential neurotropism of the new coronavirus. Methods We describe a clinical case of TN during COVID-19 and we discuss the differential diagnosis and the potential pathogenic mechanism according to the literature. Results A 65-year-old man with general malaise and typical respiratory symptoms of COVID-19, who presented with paroxysmal lancinating pain in the right V1 trigeminal territory without other neurological symptoms. General blood test and neuroimaging study were normal. A rapid test showed positive IgG and IgM serologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was diagnosed with TN secondary to a viral infection by SARS-CoV-2. Facial pain resolved with the improvement of COVID-19. Conclusions The new coronavirus SARS-CoV-2 is a possible etiology of secondary TN. Nevertheless, more studies are needed to elucidate the neuropathology of this viral infection.

关键词： Argininemia   Arginase deficiency   Urea cycle disorders   Spastic diplegia  

摘要： Argininemia or hyperargininemia is a urea cycle disorder caused by deficiency of the enzyme arginase 1. It is inherited in an autosomal recessive fashion. It commonly leads to spastic diplegia in childhood, but other important features include cognitive deterioration and epilepsy. Unlike other disorders of the urea cycle, hyperammonemia is not prominent. The authors report three siblings with genetically proven argininemia who presented with diverse phenotypes but with spasticity being a common feature. Sibling 1 developed motor regression in early childhood, sibling 2 developed delayed motor milestones from early infancy, whereas sibling 3 had global developmental delay in late infancy after a period of normal development. All siblings had mild hyperammonemia only. Early recognition is imperative, not only to initiate ammonia scavenging therapy which may lead to definite clinical improvement, but also to provide genetic counselling.