关键词： French consensus   Melatonin   Alzheimer disease   MCI   REM sleep behavior disorder   Insomnia  

摘要： The French Medicine and Research Sleep Society had organized a consensus conference about sleep/wake circadian rhythms and their disorders. During this conference a subgroup of 11 sleep doctors/researchers looked specifically at the use of MEL in different pathologies. This article gives a summary of the main results of MEL therapy in some neurological diseases and insomnia approved by this consensus group. Exogenous MEL, which crosses the blood-brain barrier, has been used as a treatment in its two available forms: an immediate release form that principally shows a chronobiotic action and a long release form that mimics the physiological MEL secretion rhythm and is used to replace reduced physiological secretion. MEL secretion decreases frequently with age, mostly in elderly insomniacs and dementia patients. Results of level A studies show that MEL therapy, used as an add-on treatment, has beneficial effects in mild cognitive impairment (MCI) and Alzheimer patients with sleep disorders in improving sleep quality and in regulating the sleep/ wake rhythm. MEL has to be prescribed as early as possible and for a long period, at a dose of 2 to 5 or 10 mg. It may have a beneficial effect on cognitive function in MCI but shows no effect in moderate to severe Alzheimer's disease. It should be emphasized that there are no serious side effects with MEL treatment. In these diseases, light therapy used 12 hours before melatonin treatment has a positive synergic effect. In REM sleep behavior disorder, immediate release MEL should be prescribed first as its side effect profile is much better than clonazepam shortly before bedtime. MEL has a good efficacy on clinical symptoms and PSG REM sleep without atonia episodes and is well tolerated. In Parkinson disease with sleepdisorders and without REM sleep behavior disorder, MEL seems to improve subjective sleep quality but no conclusions can be drawn. There is insufficient scientific proof for using MEL as a prophylactic treatment in

关键词： Child neurology   Career   Funding   Survey   Workforce   Physician-scientist  

摘要： Background: The past decades have seen a transformational shift in the understanding and treatment for neurological diseases affecting infants and children. These advances have been driven in part by the pediatric neurology physician-scientist workforce and its efforts. However, pediatric neurology research faces substantial challenges from internal and external forces including work-life balance demands, COVID-19 pandemic effects, and research funding. Understanding the impact of these challenges on the perceptions, planning, and careers of pediatric neurology physician-scientists is needed to guide the research mission. Methods: Our objective was to survey the research challenges, goals, and priorities of pediatric neurologists. In 2020 we conducted a cross-sectional, 28-question survey emailed to 1,775 members of the Child Neurology Society. Results: One hundred fifty-one individuals responded to the survey. Most respondents were grant investigators (52%) and conducted clinical research (69%). Research areas included epilepsy (23%), neurodevelopmental and autism (16%), neurocritical care and stroke (11%), neurogenetics and neurometabolics (9%), neonatal neurology (8%), and others. The most common funding source was the National Institutes of Health (37%). Shared major research concerns were funding, utilization of remote technology, overcoming disparities, natural history and multicenter studies, global neurology, and diversification of the research portfolio. Commitment to continuing and increasing research efforts was evident. Conclusions: Our survey demonstrates obstacles for physician-scientist researchers in pediatric neurology, but it also shows optimism about continued opportunity. Creative approaches to address challenges will benefit the research mission, maximize the current and future pool of researchers, and help improve the lives of children with neurological disorders. Crown Copyright (C) 2020 Published by Elsevier Inc. All rights reserved.

关键词： Amyotrophic Lateral Sclerosis   Diaphragmatic ultrasonography   Pulmonary function tests   Phrenic nerve conduction  

摘要： Background. - Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. Methods. - In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. Results. - Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N = 8), encephalopathy (N = 6), cerebrovascular events (ischemic strokes N = 4 and vein thromboses N = 2), other central nervous system (CNS) disorders (N = 4), and Guillain-Barre ' syndrome (N = 2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. Conclusions. - Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. AntiSARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations. (C) 2021 Elsevier Masson SAS. All rights reserved.

关键词： Safinamide   Developmental history   Parkinson's disease   Epilepsy   MAO-B  

摘要： The discovery and development of safinamide, an alpha-aminoamide, has been a valuable addition to the existing clinical management of Parkinson's disease (PD). The journey of safinamide dates back to the year 1983, when an alpha-aminoamide called milacemide showed a weak anticonvulsant activity. Milacemide was then structurally modified to give rise to safinamide, which in turn produced robust anticonvulsant activity. The underlying mechanism behind this action of safinamide is attributed to the inhibition of voltage gated calcium and sodium channels. Moreover, owing to the importance of ion channels in maintaining neuronal circuitry and neurotransmitter release, numerous studies explored the potential of safinamide in neurological diseases including PD, stroke, multiple sclerosis and neuromuscular disorders such as Duchenne muscular dystrophy and non-dystrophic myotonias. Nevertheless, evidence from multiple preclinical studies suggested a potent, selective and reversible inhibitory activity of safinamide against monoamine oxidase (MAO)-B enzyme which is responsible for degrading dopamine, a neurotransmitter primarily implicated in the pathophysiology of PD. Therefore, clinical studies were conducted to assess safety and efficacy of safinamide in PD. Indeed, results from various Phase 3 clinical trials suggested strong evidence of safinamide as an add-on therapy in controlling the exacerbation of PD. This review presents a thorough developmental history of safinamide in PD and provides comprehensive insight into plausible mechanisms via which safinamide can be explored in other neurological and muscular diseases.

关键词： COVID-19   CSF   Autoantibody   Neurology   Encephalitis   Autoimmunity   Viral-triggered  

摘要： Background: COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity. Design: Blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies. Results: Using cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. Conclusion: The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.

摘要： The author “Sangyong Jung” would like to correct his given name from “Sangyoung” to Sangyong. The correct name should read as “Sangyong Jung”

关键词： DUSP   Mental health   Neurological diseases   Phosphatase   Psychiatric disorders  

摘要： The dual-specificity phosphatase (DUSP) family includes a heterogeneous group of protein phosphatases that dephosphorylate both phospho-tyrosine and phospho-serine/phospho-threonine residues within a single substrate. These protein phosphatases have many substrates and modulate diverse neural functions, such as neurogenesis, differentiation, and apoptosis. DUSP genes have furthermore been associated with mental disorders such as depression and neurological disorders such as Alzheimer's disease. Herein, we review the current literature on the DUSP family of genes concerning mental and neurological disorders. This review i) outlines the structure and general functions of DUSP genes, and ii) overviews the literature on DUSP genes concerning mental and neurological disorders, including model systems, while furthermore providing perspectives for future research.

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/).