关键词： DUSP1   Microglia   miR-429   Neuroinflammation   Traumatic brain injury  

摘要： Background: Neuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Previous studies demonstrate that miR-429 is up-regulated in the brain lesions of TBI mice, while its role in regulating neuroinflammation and brain injury remains largely unknown. Method: The expression of miR-429 in LPS-activated microglia and microglia in TBI model was detected by RT-PCR. The effects of miR-429 inhibitors on LPS-activated microglia in vitro as well as neurological recovery and post-traumatic neuroinflammatory response in TBI model mice were detected in vivo. Results: LPS and TBI significantly induce the up-expression of miR-429, inflammatory cytokines, MAPK-p38 and phosphorylated NF-κB in microglia, which were all inhibited by miR-429 inhibitors. Meanwhile, miR-429 inhibitors also attenuated the neurological impairment in TBI mice. Bioinformatics analysis showed that miR-429 could target and inhibit the expression of dual specificity protein phosphatase 1 (DUSP1), thus inhibiting the expression of MAPK-p38 and phosphorylated NF-κB. Conclusion: miR-429 plays a pro-inflammatory role in activated microglia by targeting DUSP1 signaling pathway. Inhibiting miR-429 can attenuate the inflammatory response of microglia and TBI-mediated brain damage. © 2019 The Authors

关键词： IgM   neuropathy   rituximab   MYD88   B cell  

摘要： IgM paraprotein-associated peripheral neuropathy (PN) in patients without overt evidence of lymphoma is a recognised clinical entity of unknown aetiology. Interrogating the bone marrow B-cell or plasma cell clones underlying paraproteinemic neuropathies may improve our understanding of both pathogenesis and treatment options. This retrospective observational analysis of IgM paraprotein-associated PN identified five patients with small pathological MYD88 L265P and CD20-positive B-cell clones in their bone marrow using multi-parametric flow cytometry, who have shown durable neurological response to rituximab. We posit that multi-parametric flow cytometry may be instrumental in identifying the cellular source of the paraprotein in IgM paraprotein-associated PN, and thus directing appropriate immunomodulatory therapy. Further understanding of these small pathological B-cell clones may also provide additional insight into mechanisms of monoclonal gammopathy of clinical significance overall.

关键词： mental health   mental disorders   substance use disorders   Global Burden of Disease   North America  

摘要： Objective: To estimate the burden of mental, neurological, substance use disorders and self-harm (MNSS) in Canada, Mexico, and the United States. Method: We extracted 2017 data from the Global Burden of Disease online database. Based on a previously developed framework to classify and aggregate the burden of specific disorders and symptoms, we reestimated the MNSS burden to include suicide, alcohol use, drug use, specific neurological, and painful somatic symptom disorders. We analyzed age-sex-specific patterns within and between countries. Results: The MNSS burden is the largest of all disorder groupings. It is lowest in Mexico, intermediate in Canada, and highest in the United States. Exceptions are alcohol use, bipolar, conduct disorders, and epilepsy, which are highest in Mexico;and painful somatic syndromes and headaches, which are highest in Canada. The burden of drug use disorders in the United States is twice the burden in Canada, and 7 times the burden in Mexico. MNSS become the most burdensome of all disorder groups by age 10, staying at the top until age 60, and show a distinct pattern across the lifetime. The top three MNSS disorders for men are a combination of substance use disorders and self-harm (United States), with the addition of painful somatic syndromes (Canada), and headaches (Mexico). For women, the top three are headaches and depression (all countries), drug use (United States), neurocognitive disorders (Mexico), and painful somatic syndromes (Canada). Conclusion: MNSS are the most burdensome disease grouping and should be prioritized for funding in Canada, Mexico, and the United States.

摘要： The first years of life constitute a crucial period for neurodevelopment and a window of opportunity to develop new strategies to prevent neurological and mental diseases. Different studies have shown the influence of gut bacteria in neurogenesis and a functional relationship between gut microbiota and the brain, known as 'gut-brain axis', in which the intestinal microbiota is proposed to play a key role in neurophysiological processes. It has been observed that certain microbiome metabolites could be related to the development of neurological disorders through mechanisms still unknown. Then, more studies are needed to broaden the knowledge regarding the relationship between the Central Nervous System and the gastrointestinal tract, which could help to develop new preventive and treatment protocols.

关键词： Conversion disorder   functional motor disorder   functional neurological disorder  

摘要： Background Functional neurological disorder (FND), previously known as conversion disorder, is common and often results in substantial distress and disability. Previous research lacks large sample sizes and clinical surveys are most commonly derived from neurological settings, limiting our understanding of the disorder and its associations in other contexts. We sought to address this by analysing a large anonymised electronic psychiatric health record dataset. Methods Data were obtained from 322 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who had an ICD-10 diagnosis of motor FND (mFND) (limb weakness or disorders of movement or gait) between 1 January 2006 and 31 December 2016. Data were collected on a range of socio-demographic and clinical factors and compared to 644 psychiatric control patients from the same register. Results Weakness was the most commonly occurring functional symptom. mFND patients were more likely to be female, British, married, employed pre-morbidly, to have a carer and a physical health condition, but less likely to have had an inpatient psychiatric admission or to receive benefits. No differences in self-reported sexual or physical abuse rates were observed between groups, although mFND patients were more likely to experience life events linked to inter-personal difficulties. Conclusions mFND patients have distinct demographic characteristics compared with psychiatric controls. Experiences of abuse appear to be equally prevalent across psychiatric patient groups. This study establishes the socio-demographic and life experience profile of this understudied patient group and may be used to guide future therapeutic interventions designed specifically for mFND.

关键词： Stroke   ischemic stroke   sleep apnea   sleep breathing disorder   early neurological deterioration  

摘要： Background and purpose: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients. Methods: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission. Results: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI >= 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI >= 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024;95% confidence interval 1.006 to 1.042;P = .008). Conclusions: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END.

摘要： Research into the role of the gut microbiome in modulating brain function has rapidly increased over the past 10 years, albeit chiefly in animal models. Increasing dinical and preclinical evidence implicates the microbiome as a possible key susceptibility factor for neurological disorders, including Alzheimer's disease, autism spectrum disorder, multiple sclerosis, Parkinson's disease, and stroke. Cross-sectional dinical studies are bolstering the concept of altered microbial composition contributing to the pathophysiology of such diseases. However, the field is nascent, and interpretation of such data is often difficult given that the composition of the microbiome is influenced by various factors such as diet and exercise. Longitudinal studies and randomised controlled trials in humans are needed to find out if targeting the microbiome can yield novel therapeutic strategies. Systems biology approaches will also be important in integrating such data with genomic and metabolomic datasets from clinical cohorts with neurological disease to help guide individual treatment selection.

关键词： Uganda   Neurological illness   Neurological infections   Stroke   Head trauma   Global neurology  

摘要： Background While the burden of neurologic illness in developing countries is increasing, less is known about mortality among patients admitted to sub-Saharan African hospitals with neurologic disease. We sought to characterize the rate and patient-level predictors of in-hospital mortality in a Ugandan Neurology ***. Methods Data was prospectively collected on 335 patients admitted to the Neurology ward of Mulago Hospital, Kampala, Uganda. Kaplan-Meier survival curves and multivariate COX proportional hazard modeling were used to assess survival. Results Within our sample (n = 307), 35.8% received no diagnosis at time of hospital admission. Stroke (27.3%), head trauma (19.6%), and malaria (16.0%) were the most common diagnoses. Among the 56 (18.5%) patients who died during the index hospitalization, the most common diagnosis at admission and at death was stroke. Adjusted regression analysis showed that patients without a diagnosis at time of death (HR = 7.01 [2.42-20.35], p < .001) and those with diagnoses of infections (HR = 5.21 [2.16-12.58], p = <.001), stroke (HR = 2.69 [1.20-6.04], p = .017), or head trauma (HR = 3.39, [1.27-9.07], p = 0.15) had worse survival. Conclusions In-hospital mortality affected nearly 20% of the cohort, with worse survival among those without a diagnosis and with infections, stroke, head trauma. Future work should identify reasons for increased mortality among these high-risk groups and implement targeted interventions.

关键词： Carbon monoxide poisoning   delayed neurological sequelae   Tau protein   TDZD-8   GSK-3 beta  

摘要： Objective: Acute carbon monoxide (CO?poisoning can cause delayed neurological sequelae (DNS). Glycogen synthase kinase 3 beta (GSK-3 beta) /Tau protein pathway is reported to play a key role in neurological abnormalities. In the present study, we aimed to determine the role of GSK-3 beta/Tau in DNS following acute CO poisoning. Methods: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a specific non-competitive inhibitor of GSK-3 beta, was used to inhibit GSK-3 beta. Twenty-four male Sprague-Dawley rats were randomly assigned to the three groups: Control group, CO group and CO-TDZD-8 group. Rats breathed 1000 ppm CO for 40 minutes and then 3000 ppm for up to 20 minutes until they lost consciousness. TDZD-8 (1 mg/kg) was administered intravenously three times after the end of CO exposure at 0, 24, 48 hours late. Learning and memory abilities were observed using the Morris Water Maze (MWM). Brain histological changes were evaluated by hematoxylin-eosin staining. Moreover, the expression levels of Tau and GSK-3 beta were detected after acute carbon monoxide poisoning. Results: TDZD-8 significantly attenuated the learning and memory dysfunction induced by acute CO poisoning, ameliorated the histology structure of damaged neural cells in cortex and hippocampus CA1 area. TDZD-8 clearly decreased p-Tau expression, reversed the reduction of p-GSK-3 beta induced by acute CO poisoning. Conclusions: The therapeutic effect of TDZD-8 in alleviating DNS caused by acute CO poisoning is related to the inactivation of Tau by intensifying the level of GSK-3 beta phosphorylation.

关键词： Functional Neurology   Chiropractic   Critical review   Evidence   Effect   Benefit  

摘要： Background Functional Neurology (FN), founded by FR Carrick, is an approach used by some chiropractors to treat a multitude of conditions via the nervous system including the brain. However, it seems to lack easily obtainable scientific evidence for its clinical validity. Objectives 1) To define the topics of FR Carrick's publications, 2) to define the proportion of articles that are research studies, case studies, abstracts and conference papers, 3) to define how many of these are clinical research studies that purported or appeared to deal with the effect or benefit of FN, 4) in these studies, to establish whether the design and overall study method were suitable for research into the effect or benefit of FN, and 5) to describe the evidence available in relation to the clinical effect or benefit of FN, taking into account seven minimal methodological criteria. Method A literature search was done on Pubmed from its inception till October 2018, supplemented by a search on Scopus and ResearchGate to find all published documents by FR Carrick. We identified their types and topics, retaining for a critical review full text scientific articles appearing to test effect/benefit of FN procedures, subjecting them to a basic quality assessment (scoring 0-7). Results from studies of methodologically acceptable standard would be taken into account. Results We found 121 published texts, 39 of which were full scientific research articles. Of these, 23 dealt with topics relating to FN. Fourteen articles reported on clinical validity but only seven included a control group. The methodological quality of these seven articles was low, ranging between 1.5-4 out of 7. We therefore did not further report the outcomes of these studies. Conclusion We found no acceptable evidence in favour of effect/benefit of the FN approach. We therefore do not recommend its promotion as an evidence-based method. Further research on this topic should be conducted in collaboration with independent scient