关键词： Contrast media   gadolinium   magnetic resonance imaging  

摘要： Background: Magnetic resonance imaging (MRI) enhanced with gadolinium-based contrast agents (GBCAs) is an essential tool in the diagnosis and management of many neurologic diseases, including multiple sclerosis, brain tumors, and infections. The clinical utility of GBCAs is evidenced by their widespread use. GBCAs are produced in macrocyclic and linear forms. Since 2014, evidence has suggested that repeated administration of GBCAs can lead to gadolinium deposition in the brain. Methods: We review the literature on gadolinium deposition, including both animal and human studies, as well as the literature on GBCA-associated health outcomes. Additionally, we summarize and discuss the updated medical society recommendations and perspectives on GBCA use in clinical practice. Results: The first publication reporting gadolinium deposition in the human brain was published in 2014. Since that seminal report, multiple studies have demonstrated that exposure to linear GBCAs is associated with gadolinium deposition in the dentate nucleus and globus pallidus as seen on brain MRI. Macrocyclic GBCA exposure has not convincingly been associated with gadolinium deposition evident on brain MRI. Conclusion: Clear evidence demonstrates that GBCAs lead to gadolinium deposition in the brain in a dose-dependent manner;however, only linear GBCAs have been associated with gadolinium deposition visualized on MRI. To date, no evidence links gadolinium deposition with any adverse health outcome. Updated medical society guidelines emphasize the importance of an individualized risk-benefit analysis with each administration of GBCAs.

关键词： Third-wave therapies   acceptance and commitment therapy   mindfulness   transdiagnostic   neurological condition   systematic review  

摘要： Background: Adults with long-term neurological conditions can face complex challenges including anxiety and depression. Emerging research suggests the utility of third-wave approaches (the third development of psychotherapies) in working transdiagnostically with these difficulties. Aims: This systematic review sought to summarise and appraise the quality of published empirical studies using third-wave therapies such as Compassion Focused Therapy;Acceptance and Commitment Therapy;and Mindfulness-Based Cognitive Therapy or Mindfulness-Based Stress Reduction. Method: Review procedures followed PRISMA guidelines, with 437 abstracts screened, 24 full-text articles retrieved and 19 studies found to meet inclusion criteria. Six out of seven randomised studies had unclear or high risk of bias, whilst the majority of non-randomised studies were considered moderate quality. Results: Overall, studies reported a statistically significant reduction in emotional distress. Of the 13 studies that used model-specific process measures, 10 found statistically significant improvements in transdiagnostic factors. Discussion: The findings indicate that third-wave therapies show promise in addressing transdiagnostic difficulties within neurological conditions. A number of methodological and conceptual issues for the included studies were highlighted during the quality appraisal process. Clinical implications include consideration of intervention length and use of outcome measures. Research implications are discussed by considering the progressive stages of development for behavioural treatments.

关键词： Maternal substance use   Dubowitz neurological examination   Neonatal development   Risk pregnancy  

摘要： Background: There is a special concern regarding substance using pregnant women due to the possible adverse effects on the infant. While the immediate effects of prenatal substance exposure are well known, the long-term data on the infants' neurodevelopment is inconclusive. Aims: The purpose of this study was to assess early neurobehavior of infants of mothers with substance use using the Dubowitz examination and to follow their neuromotor development until one year of age. Study design and subjects: Ninety-five pregnant women with a recent history of substance use were recruited and followed up at the maternity outpatient clinic. Follow-up data was collected from hospital records and maternal interviews. The Dubowitz neurological examination was performed to the 54 clinically healthy term infants. The results were converted into optimality scores and compared to normative values from clinically healthy term infants derived from a separate normative population. The infant's neuromotor development was followed up to one year of age. Results: Only 7% of the infants born to women with recent or current substance use reached optimal scores (<30.5) in the Dubowitz neurological examination compared to 95% reported in normative population. Sixty-three percent of the newborns needed follow-up based on physiotherapeutic assessment of neurobehavior. By 12 months of age, the neuromotor status of 88% (n = 30) of these infants was found normal. Conclusions: A high percentage of infants of mothers who were referred prenatally to hospital due to substance use showed suboptimal neurological findings during their first days of life.

关键词： Uncontrolled manifold   Synergy   Neurological impairment  

摘要： Background: Analysis of sensorimotor synergies has been greatly advanced by the Uncontrolled Manifold (UCM) approach. The UCM method is based on partitioning inter-trial variance displayed by elemental variables into 'good' (V-UCM) and 'bad' (V-ORT) variability that, respectively, indicate maintenance or loss of task stability. In clinical populations, these indices can be used to investigate the strength, flexibility, stereotypy and agility of synergistic control. Research question: How are synergies affected by neurological impairment in adults? Specifically, this study aimed to determine i) the impact of pathology on V-UCM, V-ORT, and their ratio (synergy index);ii) the relationship between synergy indices and functional performance;iii) changes in anticipatory synergy adjustments (ASAs);and iv) the effects of interventions on synergies. Methods: Systematic review of UCM studies on adults with neurological impairment. Results: Most of the 17 studies had moderate to high quality scores in the adapted Critical Review Form and the UCM reporting quality checklist developed for this review. i) Most of the studies found reduced synergy indices for patients with Parkinson's disease (PD), olivo-ponto-cerebellar atrophy, multiple sclerosis and spinocerebellar degeneration, with variable levels of change in V-UCM and V-ORT. Reduction in synergy indices was not as consistent for stroke, in three out of six studies it was unchanged. ii) Five of seven studies found no significant correlations between scores on motor function scales and UCM indices. iii) Seven studies consistently reported ASAs that are smaller in magnitude, delayed, or both, for patients compared to healthy controls. iv) Two studies reported increased synergy indices, either via increase in V-UCM or decrease in V-ORT, after dopaminergic drugs for patients with PD. There were similar synergy indices but improved ASAs after deep brain stimulation for patients with PD. Significance: UCM can provide reliable and

摘要： It is increasingly recognized that there is significant heterogeneity in phenotype and clinical trajectories both in Alzheimer’s as well as in Parkinson’s disease. Up to 25% of Alzheimer’s disease (AD) cases do not show the typical neuropathology. Recently subtypes and atypical non-amnestic AD presentations have been formalized in the International Working Group (IWG) clinical diagnosis criteria. Clinical diagnosis of atypical AD has significantly been improved by the availability of biomarkers, including cerebrospinal fluid levels of Aβ42, total tau (t-tau) and phosphorylated tau181 (p-tau), MRI volumetric estimation of hippocampal and medial temporal atrophy, and amyloid brain PET imaging. We will review the typical and atypical forms of AD from these varied perspectives to help improve diagnostic confidence among clinicians. Special attention will be given to language variant of Alzheimer’s disease. A predominant deficit in the language domain is a key feature of primary progressive aphasia but language impairment is commonly present in Alzheimer’s disease. International diagnostic criteria for PPA and its three variants (agrammatic, logopenic, semantic) were published relatively recently in 2011. Since then, studies have investigated the validity of these criteria in classifying patients which includes clinical symptoms, neurocognitive presentations, distinct MRI signatures, and neuropathological differences. In this session, we will review the subtypes of PPA using the above parameters to assist clinicians in diagnosis of these conditions. Special attention will be given of logopenic PPA a syndrome frequently seen in atypical Alzheimer’s disease. Another common neurodegenerative disorder, Parkinson’s disease (PD) conceptualized as predominantly movement disorder presents with myriad of atypical features predominantly psychiatric in nature. Psychosis is one of the most debilitating symptoms of PD, as it is an independent risk factor for nursing home placements,

关键词： Herpes simplex virus   STING   DMXAA   Immunotherapy antiviral therapy  

摘要： Herpes simplex virus (HSV) - 1 is the most common cause of sporadic viral encephalitis and accounts for 5-10% of cases worldwide. A key factor in host control of viral infection is the initiation of the interferon (IFN) response, mediated in part by the stimulator of interferon genes (STING) pathway. In these studies, we examined the ability of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a STING agonist, to protect against HSV-1 infection. DMXAA reduced viral replication through increased production of type I IFN in vitro. Furthermore, administration of DMXAA to HSV-1 infected mice resulted in a reduction of viral burden in the peripheral and central nervous systems. This reduced viral burden also correlated with increased survival of DMXAA-treated infected mice. These results therefore demonstrate the potential of STING agonists for immunotherapy against HSV-1.

关键词： Epilepsy   Major depressive disorder   Psychological interview   Meta-analysis  

摘要： Background and purpose: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a useful inventory for screening major depressive disorder (MDD) in people with epilepsy (PWE). The cutoff score for detecting MDD has been reported with the range of >11 to >16. The aim of this study was to find optimal cutoff score of the NDDI-E for MDD detection by combining the raw data from previous studies. Methods: We searched MEDLINE, EMBASE, Cochrane Library, Web of Science, and SCOPUS to identify proper studies. Original researches, which tested the accuracy of NDDI-E for MDD detection in adult PWE, were recruited. We included the studies in which MDD was diagnosed by a gold standard structural interview, the Mini International Neuropsychiatric Interview (MINI). In addition, we included only the studies providing enough information for meta-analysis: number of PWE with MDD, number of total PWE, and sensitivity (Se) and specificity (Spe) for each cutoff score. After collecting data from included studies, we performed a diagnostic test accuracy (DTA) meta-analysis using bivariate model. Results: We identified 13 validation studies conducted in outpatient epilepsy clinic setting. As summary estimates of test accuracy measures, the Se, Spe, and diagnostic odds ratio (DOR) of NDDI-E for MDD detection were 0.81, 0.84, and 22.48, respectively. The analysis using the multiple thresholds model showed that the NDDI-E score of 13.2 was the best fit for MDD detection. When analyzing only with the seven data sets of the cutoff score >13, the Se, Spe, and DOR were 0.87, 0.80, and 25.72, respectively. Conclusions: The optimal NDDI-E cutoff score for MDD detection is >13. The information provided by this DTA meta-analysis will be a useful reference for applying NDDI-E in geographic areas where no NDDI-E validation studies have been conducted for their languages. (C) 2018 Elsevier Inc. All rights reserved.

关键词： quality of Life   patient-reported outcomes   neurofibromatosis type 1   plexiform neurofibrom   pediatric  

摘要： Objective To assess the health-related quality of life of children with neurofibromatosis type 1-related plexiform neurofibromas (pNF) using a battery of patient-reported outcome measures selected based on a conceptual framework derived from input by patients, parents, and clinicians regarding the most important pNF symptoms and concerns. Study design There were 140 children with pNF ages 8-17 years who completed the Patient-Reported Outcomes Measurement Information System (including domains anxiety, depressive symptom, psychosocial stress experiences. fatigue, pain interference, meaning and purpose. positive affect. peer relationships, physical functionmobility) and Quality of Life in Neurological Disorders measurement system (stigma) via an online platform. T-scores for each measure were compared with US population norms. Results Children with pNF reported significantly worse scores than the population norms on 8 of 10 domains. Children with at least 1 family member having a diagnosis of neurofibromatosis type 1 and those having pain reported significantly worse symptoms and functioning on all domains. Boys reported significantly worse pain interference, stigma, meaning and purpose, mobility function, and upper extremity function than girls. Conclusions Children with pNF experience significantly worse health-related quality of life on all but 1 domain, highlighting the importance of monitoring children's quality of life over time in clinical research and practice. Future research should evaluate the replicability of these findings and evaluate the validity of the Patient-Reported Outcomes Measurement Information System and Quality of Life in Neurological Disorders measurement system in relation to clinical characteristics among children with pNF.

关键词： ALZHEIMER'S disease treatment   AMYLOID  

摘要： The article offers pharmaceutical industry news brief as of March 2019. Topics discussed include faliure of amyloid targeting b-secretase (BACE) inhibitors for treatment Alzheimer's disease in neurolgy, Ipsen and Clementia Pharmaceuticals have entered into an agreement for Ipsen to acquire Clementia Pharmaceuticals and Charles River Laboratories International, Inc. has signed a binding offer to acquire Citoxlab.

关键词： Bilateral common carotid artery occlusion   Ischemic stroke   Jobelyn®   Oxidative stress   Pro-inflammatory cytokines  

摘要： The effects of Jobelyn® (JB) on neurological deficits and biochemical alterations associated with ischemic stroke induced by bilateral common carotid artery occlusion (BCCAO) in rats were investigated in this study. Male Wistar rats were divided into five groups (n = 8): group 1 served as Sham control;group 2, which served as negative control received normal saline while groups 3–5 were given JB (25, 50 and 100 mg/kg, p.o) daily for 28 days. Then, rats in groups 2–5 were subjected to BCCAO for 30 min and reperfusion afterwards. Neurological deficits were assessed 3 h post-reperfusion using a 9-point neurological scoring scale. The levels of biomarkers of oxidative stress and pro-inflammatory cytokines (tumour necrotic factor-α and interleukin-6), expressions of immunopositive cells of nuclear factor-kappa B (NF-κB) and acetyl-cholinesterase (AChE) activity were determined in brain tissues. Histology of the striatum, prefrontal cortex (PFC) and hippocampus (CA1) was also evaluated. JB improved BCCAO-induced neurological deficits and attenuated increased oxidative stress and AChE activity in rats subjected to BCCAO (p < 0.05). Increased brain levels of tumour necrotic factor-α and interleukin-6 as well as expressions of immunopositive cells of NF-κB were decreased by JB. JB reduced brain damage and also increased population of viable neurons in the striatum, PFC and hippocampus of ischemic stroke rats. These findings suggest that the positive effect of JB on neurological function in rats with ischemic stroke may be related to inhibition of oxidative stress, release of pro-inflammatory cytokines and expressions of immunopositive cells of NF-κB. © 2018 Elsevier B.V.