关键词： acute flaccid paralysis   encephalitis   enterovirus   meningitis   systematic review  

摘要： Enteroviruses are RNA viruses found as commensals in the human gut and respiratory system, which may cause a wide spectrum of disease. Enteroviruses may cause severe neurologic complications including acute flaccid paralysis (AFP) and encephalitis and are the most commonly diagnosed agents of viral meningitis. Outbreaks of more severe disease are often associated with particular genotypes, such as enterovirus-A71 causing rhombencephalitis and AFP. There are more than 300 described genotypes of human enterovirus, with overlaps in clinical phenotypes between genotypes, and uncertainty about which genotypes are more prevalent in neurological manifestations. A systematic review of observational studies was conducted to evaluate the most prevalent enterovirus genotypes causing AFP, encephalitis, and meningitis. The genotyping methods and sampling sites were compiled as secondary outcomes. Sources included MEDLINE, Embase (publications until January 2019), and references selected from included studies. Meta-analyses using a random effects model were performed to calculate the pooled proportion of enterovirus genotypes in each disease. Ninety-six publications met the eligibility criteria, comprising 3779 AFP cases, 1140 encephalitis cases, and 32 810 meningitis cases. Enterovirus-A71 was most frequently associated with AFP (pooled proportion 0.12, 95% CI, 0.05-0.20) and encephalitis (0.77, 95% CI, 0.61-0.91). Echovirus 30 (0.35, 95% CI, 0.27-0.42) was the most predominant genotype in meningitis cases. Genotypes were most commonly determined using VP1 RT- reverse transcription-polymerase chain reaction, and most samples assessed were cerebrospinal fluid. With the emergence of enteroviruses as an increasing cause of neurological diseases, surveillance and testing need to increase to identify the aetiology of the most common and most severe disorders.

关键词： Autotaxin   Lysophospholipase D   Inflammatory neuropathic pain   Glioblastoma multiforme   Hemorrhagic hydrocephalus   Schizophrenia   Multiple sclerosis   Alzheimer's disease   Metabolic syndrome-induced brain damage   Traumatic brain injury   Hepatic encephalopathy induced cerebral edema   Macular edema   Major depressive disorder   Stress-induced psychiatric disorder   Alcohol-induced brain damage   HIV-induced brain injury   Pruritus   Peripheral nerve injury  

摘要： Autotaxin (ATX) is a soluble extracellular enzyme that is abundant in mammalian plasma and cerebrospinal fluid (CSF). It has two known enzymatic activities, acting as both a phosphodiesterase and a phospholipase. The majority of its biological effects have been associated with its ability to liberate lysophosphatidic acid (LPA) from its substrate, lysophosphatidylcholine (LPC). LPA has diverse pleiotropic effects in the central nervous system (CNS) and other tissues via the activation of a family of six cognate G protein-coupled receptors. These LPA receptors (LPARs) are expressed in some combination in all known cell types in the CNS where they mediate such fundamental cellular processes as proliferation, differentiation, migration, chronic inflammation, and cytoskeletal organization. As a result, dysregulation of LPA content may contribute to many CNS and PNS disorders such as chronic inflammatory or neuropathic pain, glioblastoma multiforme (GBM), hemorrhagic hydrocephalus, schizophrenia, multiple sclerosis, Alzheimer's disease, metabolic syndrome-induced brain damage, traumatic brain injury, hepatic encephalopathy-induced cerebral edema, macular edema, major depressive disorder, stress-induced psychiatric disorder, alcohol-induced brain damage, HIV-induced brain injury, pruritus, and peripheral nerve injury. ATX activity is now known to be the primary biological source of this bioactive signaling lipid, and as such, represents a potentially high-value drug target. There is currently one ATX inhibitor entering phase III clinical trials, with several additional preclinical compounds under investigation. This review discusses the physiological and pathological significance of the ATX-LPA-LPA receptor signaling axis and summarizes the evidence for targeting this pathway for the treatment of CNS diseases.

摘要： This article evaluates the epidemiological evidence for a relationship between vaccination and neurological disease, specifically multiple sclerosis, Guillain-Barre syndrome and narcolepsy. The statistical methods used to test vaccine safety hypotheses are described and the merits of different study designs evaluated;these include the cohort, case-control, case-coverage and the self-controlled case-series methods. For multiple sclerosis, the evidence does not support the hypothesized relationship with hepatitis B vaccine. For Guillain-Barre syndrome, the evidence suggests a small elevated risk after influenza vaccines, though considerably lower than after natural influenza infection, with no elevated risk after human papilloma virus vaccine. For narcolepsy, there is strong evidence of a causal association with one adjuvanted vaccine used in the 2009/10 influenza pandemic. Rapid investigation of vaccine safety concerns, however biologically implausible, is essential to maintain public and professional confidence in vaccination programmes.

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关键词： Neurological diseases   Epilepsy   Cerebral Palsy   Intellectual disability   Paediatric care  

摘要： The transfer of adolescents from paediatric care to adult health facilities is often difficult for the patients and their families and can lead to a breakdown in medical follow-up and therefore serious complications. Existing recommendations for the successful transition of patients with chronic disorders do not specifically address patients with handicap. Preparations for the transfer must be made well in advance. They must aim to achieve the autonomisation of adolescents by making them responsible and providing them with the knowledge that will enable them to manage their care themselves, the know-how to react appropriately if there is any change in their condition, and to move comfortably within the adult health system. This requires the active participation of the patient, his or her family and the paediatric and adult care teams. It involves multidisciplinary management plus the production and maintenance of an educational therapy programme. Finally, the identification of doctors trained in handicap, relevant sub-specialists and even expert patients could enable improvements in the continuum of complete and appropriate care for these patients within adult medicine. (C) 2019 Elsevier Masson SAS. All rights reserved.

摘要： Nowadays, the "flipped classroom" approach is taking the center stage within medical education. However, very few reports on the implementation of the flipped classroom in neurology have been published to date, and this educational model still represents a challenge for students and educators alike. In this article, neurology educators from the American Academy of Neurology's A. B. Baker Section on Neurological Education analyze reports of flipped classroom in other medical/surgical subspecialties, review the current implementation in neurology, and discuss future strategies to flip the neurology curriculum through contextualization of the benefits and the consequences. ANN NEUROL 2019

关键词： Trace element   Traumatic spinal cord injury   Neurological remission   Trauma   Selenium   Copper   Selenoprotein P   Ceruloplasmin  

摘要： Introduction: Traumatic Spinal Cord Injury (TSCI) is a severe incident resulting in loss of motor and sensory function caused by complex pathological mechanisms including massive oxidative stress and extensive inflammatory processes. The essential trace elements selenium (Se) and copper (Cu) play crucial roles as part of the antioxidant defense. Hypothesis: Remission after TSCI is associated with characteristic dynamics of early changes in serum Cu and Se status. Study design: Single-center prospective observational study. Patients and methods: Serum samples from TSCI patients were analyzed (n = 52);21 recovered and showed a positive abbreviated injury score (AIS) conversion within 3 months (G1), whereas 21 had no remission (G0). Ten subjects with vertebral fractures without neurological impairment served as control (C). Different time points (at admission, and after 4, 9, 12, and 24 h) were analyzed for total serum Se and Cu concentrations by total reflection X-ray fluorescence, and for Selenoprotein P (SELENOP) and Ceruloplasmin (CP) by sandwich ELISA. Results: At admission, CP and SELENOP concentrations were higher in the remission group (G1) than in the non-remission group (G0). Within 24 h, there were marginal changes in Se, SELENOP, Cu and CP concentrations in the groups of controls (C) and G0. In contrast, these parameters decreased significantly in G1. Binary logistic regression analysis including Cu and Se levels at admission in combination with Se and CP levels after 24 h allowed a prediction for potential remission, with an area under the curve (AUC) of 87.7% (CI: 75.1%-100.0%). Conclusion: These data indicate a strong association between temporal changes of the Se and Cu status and the clinical outcome after TSCI. The dynamics observed may reflect an ongoing redistribution of the trace elements in favor of a better anti-inflammatory response and a more successful neurological regeneration.

关键词： Epilepsy   Multiple sclerosis   Neurodegenerative diseases   Stroke  

摘要： Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Delta(9)-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.

关键词： Wilson disease   zinc   copper   subacute combined degeneration   neurological complication  

摘要： A 17-year-old female was diagnosed with Wilson disease and commenced on oral zinc therapy. She re-presented 6 months later with a fall and had classical signs of subacute combined degeneration of the spinal cord confirmed on nerve conduction studies, as a result of zinc-induced copper deficiency. After 6 months of copper therapy, she made a complete recovery with no residual neurological deficits. Early detection of zinc-induced copper deficiency and stringent follow-up mechanisms are crucial. Early initiation of copper replacement may both limit and completely reverse neurological deficits.

关键词： acid-base   diarrhea   electrolytes   enteritis   neonate   seizure-like activity  

摘要： Objective Hyponatremia and rapid correction of hyponatremia can lead to neurological abnormalities. The objective of the study was to determine whether plasma sodium concentrations (Na+) and speed of correction of hyponatremia are significantly associated with neurological abnormalities in foals. Design Retrospective cohort study 2012 to 2016. Setting Equine hospital. Animals One hundred and nine foals <6 months old with hyponatremia (Na+ concentration <= 125 mmol/L). Interventions Case records were reviewed for any foal with hyponatremia. Clinicopathological findings, presence or absence of neurological signs on the day of the lowest Na+ concentration measured and the following 5 days, diagnosis and outcome were recorded, and changes in Na+ concentration per hour were calculated for up to 5 subsequent days. Logistic regression was used to assess the association between presence or absence of neurological signs, Na+ concentration, other known risk factors for neurological dysfunction in foals, and possible confounders. Measurements and Main Results In the final multivariable model, only Na+ (odds ratio [OR]: 0.86;95% CI 0.79-0.95;P = 0.002) and BUN concentrations (OR: 1.04;95% CI: 1.02-1.06;P = 0.001) were significantly associated with neurological signs. Changes in Na+ concentrations per hour were not associated with neurological signs on any day after the lowest Na+ concentration had been measured (P = 0.18-0.82), and development of new neurological signs following correction of hyponatremia was not reported in any foal. Conclusions Na+ concentrations were associated with the development of neurological signs in hyponatremic foals. Increased BUN concentrations might contribute to neurological dysfunction, but further studies are necessary to confirm or refute these findings.