Role of oral teriflunomide in the management of multiple sclerosis

The landscape of the treatment of relapsing–remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing–remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing–remitting multiple sclerosis is discussed

Smoking cessation and the reduction of disability progression in Multiple Sclerosis: a cohort study

Background: Smoking is associated with a more severe disease course in people with multiple sclerosis (MS). The magnitude of effect of smoking cessation on MS progression is unknown. The aim of this study was to quantify the impact of smoking cessation on reaching MS disability milestones. Methods: This is a cross-sectional study with retrospective reports. A comprehensive smoking questionnaire was sent to 1270 patients with MS registered between 1994 and 2013 in the Nottingham University Hospital MS Clinics database. Demographic and clinical data were extracted from the clinical database. Cox proportional hazard regression was used to estimate effects of smoke-free years on the time to Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0. MS Impact Scale 29 (MSIS-29) and Patient Determined Disease Steps (PDDS) were used to assess the physical and psychological impact of smoking. Results: Each ‘smoke-free year’ was associated with 0.96 (95% CI: 0.95 to 0.97) times decreased risk of reaching EDSS 4.0 and 0.97 (95%CI: 0.95 to 0.98) times decreased risk of reaching EDSS 6.0. Non-smokers showed a significantly lower level of disability in all the self-reported outcomes compared with current smokers. Conclusion: The reduction in the risk of disability progression after smoking cessation is significant and time-dependent. The earlier the patients quit, the stronger the reduction in the risk of reaching disability milestones. The quantitative estimates of the impact of smoking cessation on reaching disability milestones in MS can be used in interventional trials

Coordinate based random effect size meta-analysis of neuroimaging studies

Low power in neuroimaging studies can make them difficult to interpret, and Coordinate based meta-analysis (CBMA) may go some way to mitigating this issue. CBMA has been used in many analyses to detect where published functional MRI or voxel-based morphometry studies testing similar hypotheses report significant summary results (coordinates) consistently. Only the reported coordinates and possibly t statistics are analysed, and statistical significance of clusters is determined by coordinate density. Here a method of performing coordinate based random effect size meta-analysis and meta-regression is introduced. The algorithm (ClusterZ) analyses both coordinates and reported t statistic or Z score, standardised by the number of subjects. Statistical significance is determined not by coordinate density, but by a random effects meta-analyses of reported effects performed cluster-wise using standard statistical methods and taking account of censoring inherent in the published summary results. Type 1 error control is achieved using the false cluster discovery rate (FCDR), which is based on the false discovery rate. This controls both the family wise error rate under the null hypothesis that coordinates are randomly drawn from a standard stereotaxic space, and the proportion of significant clusters that are expected under the null. Such control is necessary to avoid propagating and even amplifying the very issues motivating the meta-analysis in the first place. ClusterZ is demonstrated on both numerically simulated data and on real data from reports of grey matter loss in multiple sclerosis (MS) and syndromes suggestive of MS, and of painful stimulus in healthy controls. The software implementation is available to download and use freely

The Role of Fructose as a Cardiovascular Risk Factor: An Update

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD

The future of multiple sclerosis treatments

Introduction. There are not many conditions in which the last few decades have brought such a major change in the landscape of treatments as is the case of multiple sclerosis (MS). A number of disease modifying treatments (DMTs) are presently available for the treatment of the inflammatory phase of this disabling disease; however, the need for treating neurodegeneration and halting the progression of disability is still unmet. Areas covered: In this paper we review the available information on existing and emerging DMTs and we discuss their place within the context of different treatment strategies in MS. Expert Commentary: The future of MS treatments should include the development of new treatment strategies tackling disease progression, together with a better understanding of the side-effects and the best sequential strategy of implementation of available and emerging drugs

SVOA Neurology Sera from Patients with Multiple Sclerosis in Relapse or Remission Affect the Blood-Brain Barrier Differently: An In vitro Study

Background: Breakdown of the blood-brain barrier (BBB) constitutes a key step in the pathogenesis of multiple sclerosis(MS).Aims: To investigate whether sera from MS patients in relapse or in remission may differently affect the BBB functionand to assesses the putative barrier-restorative effects of major molecular mechanisms known to regulate BBB function.Methods: Sera were prepared by centrifugation of the whole blood samples of the study participants. A cell culture modelof human BBB, consisting of human brain microvascular endothelial cells, astrocytes and pericytes, was establishedusing transwell inserts. The integrity and function of BBB were studied by measurements of transendothelial electricalresistance (TEER) and paracellular flux of Evan’s blue-labelled albumin (EBA), respectively.Results: Sera from MS patients in relapse possessed greater levels of inflammatory cytokines (TNF- and IL-1 ), apoptoticenzyme activity (caspase-3/7) and were more disruptive of BBB as evidenced by significant decreases in TEER andincreases in EBA flux. Suppression of intracellular availability of reactive oxygen species or NADPH oxidase, Rho -kinase,protein kinase C- and matrix metalloproteinase-2 activity by specific inhibitors markedly attenuated the BBBdisruptiveeffects of sera obtained from MS patients in relapse or remission.Conclusions: A plethora of mechanisms affecting the overall status of oxidative stress, inflammation, cell viability andbasement membrane integrity appear to contribute to the BBB damage in MS patients, especially those in relapse. Effectiveinhibition of the key elements associated with these mechanisms mitigate the deleterious effects of MS patients’ seraon BBB integrity and function