Repetitive Transcranial Magnetic Stimulation, Cognition, and Multiple Sclerosis: An Overview

Multiple sclerosis (MS) affects cognition in the majority of patients. A major aspect of the disease is brain volume loss (BVL), present in all phases and types (relapsing and progressive) of the disease and linked to both motor and cognitive disabilities. Due to the lack of effective pharmacological treatments for cognition, cognitive rehabilitation and other nonpharmacological interventions such as repetitive transcranial magnetic stimulation (rTMS) have recently emerged and their potential role in functional connectivity is studied. With recently developed advanced neuroimaging and neurophysiological techniques, changes related to alterations of the brain’s functional connectivity can be detected. In this overview, we focus on the brain’s functional reorganization in MS, theoretical and practical aspects of rTMS utilization in humans, and its potential therapeutic role in treating cognitively impaired MS patients

Reporting quality of randomized controlled trials in Restless Legs Syndrome based on the CONSORT statement

Randomized Controlled Trials (RCTs) are the cornerstone of modern medical research and their reporting may not always be optimal. The CONSORT (CONsolidated Standards of Reporting Trials) statement is an evidence-based means of improving and assessing the quality of these trials. The aim of the present study was to assess the reporting quality of published RCTs on the Restless Legs Syndrome (RLS) based on a checklist stemming from the CONSORT statement. RCTs involving patients with RLS were searched for into medical electronic databases. Inclusion criteria were English language of publication and the randomization of RLS patients in a minimum of two treatment cohorts of different medicinal orientations. The reporting quality was evaluated by the means of the aforementioned 38-item CONSORT checklist and the articles were divided into three 6-year periods. Descriptive statistics were used to make the comparisons. Fifty four (54) eligible trials were found, published in 21 different scientific journals. The average CONSORT compliance score was 56.6% (23.68%-84.21%). CONSORT-endorsing journals had a mean CONSORT compliance of 58.47%, whereas non-endorsing journals 50.4%. The median CONSORT compliance for articles published in low (IF7) ranked journals was 52.63%, 56.57% and 59.21% respectively. Throughout the whole 1998-2016 period, 14 items (36.8%) were reported in >75% of the articles. This study shows that the reporting of RLS-related RCTs is suboptimal, regardless of the time period, the quality of the publishing journal and the endorsing or not of the CONSORT statement

Cognitive Impairment in Heart Failure

Cognitive impairment (CI) is increasingly recognized as a common adverse consequence of heart failure (HF). Although the exact mechanisms remain unclear, microembolism, chronic or intermittent cerebral hypoperfusion, and/or impaired cerebral vessel reactivity that lead to cerebral hypoxia and ischemic brain damage seem to underlie the development of CI in HF. Cognitive decline in HF is characterized by deficits in one or more cognition domains, including attention, memory, executive function, and psychomotor speed. These deficits may affect patients' decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms. CI may have fluctuations in severity over time, improve with effective HF treatment or progress to dementia. CI is independently associated with disability, mortality, and decreased quality of life of HF patients. It is essential therefore for health professionals in their routine evaluations of HF patients to become familiar with assessment of cognitive performance using standardized screening instruments. Future studies should focus on elucidating the mechanisms that underlie CI in HF and establishing preventive strategies and treatment approaches

Risk Factor Genes in Patients with Dystonia: A Comprehensive Review

Background: Dystonia is a movement disorder with high heterogeneity regarding phenotypic appearance and etiology that occurs in both sporadic and familial forms. The etiology of the disease remains unknown. However, there is increasing evidence suggesting that a small number of gene alterations may lead to dystonia. Although pathogenic variants to the familial type of dystonia have been extensively reviewed and discussed, relatively little is known about the contribution of single-nucleotide polymorphisms (SNPs) to dystonia. This review focuses on the potential role of SNPs and other variants in dystonia susceptibility. Methods: We searched the PubMed database for peer-reviewed articles published in English, from its inception through January 2018, that concerned human studies of dystonia and genetic variants. The following search terms were included: “dystonia” in combination with the following terms: 1) “polymorphisms” and 2) “SNPs” as free words. Results: A total of 43 published studies regarding TOR1A, BDNF, DRD5, APOE, ARSG, NALC, OR4X2, COL4A1, TH, DDC, DBH, MAO, COMT, DAT, GCH1, PRKRA, MR-1, SGCE, ATP1A3, TAF1, THAP1, GNAL, DRD2, HLA-DRB, CBS, MTHFR, and MS genes, were included in the current review. Discussion: To date, a few variants, which are possibly involved in several molecular pathways, have been related to dystonia. Large cohort studies are needed to determine robust associations between variants and dystonia with adjustment for other potential cofounders, in order to elucidate the pathogenic mechanisms of dystonia and the net effect of the genes

Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab

Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer : a case control study

Ajuts: the present study was developed on a self-funding base, using a personal budget of Evangelia Pavlidou for the reagents used in the laboratory analysis.Background: the aim of the study was to evaluate the association of two SNPs of EVER1/2 genes' region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population. -Methods: among the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis. - Results: the results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients' subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference. Conclusions: None of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer

Biologics targeting IL-17 sharply reduce circulating T follicular helper and T peripheral helper cell sub-populations in psoriasis

IntroductionCirculating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3+CD4+CXCR5+) and cTph (CD3+CD4+CXCR5-PD-1hi) cells..ResultsFlow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS+ and ICOS+PD-1+ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS+ and ICOS+PD-1+ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics.ConclusionEarly anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations