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The diagnosis of multiple sclerosis (MS) in women of reproductive age is associated with many uncertainties regarding childbearing and lactation. Pregnancies of MS patients are not usually considered high-risk pregnancies per se. The likelihood of pregnancy complications or adverse pregnancy outcomes is not increased by the disease; however, a careful planning of pregnancy is important in order to choose the treatment option with the greatest benefit for the mother and the least possible risk for the baby. For highly active courses of the disease, anti-CD20 antibodies, cladribine, or continued administration of natalizumab show the best data. Patients with MS can be supported in their desire to breastfeed. If women have had a very active disease course, it is recommended that treatment should be started as soon as possible postpartum. Interferon-beta preparations, glatiramer acetate and ofatumumab are also approved for use during breastfeeding but off-label breastfeeding is also possible with other monoclonal antibodies., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Post-marketing studies, including registries, mark an indispensable step in the establishment of drug side-effect profiles. In recent years, the inclusion of the patients' perspective has gained increasing relevance regarding pharmacovigilance., Objective: Primary objective of this study was to analyse the concordance of subjectively experienced symptoms by multiple sclerosis (MS) patients treated with immunotherapy and the adverse events reported by their treating physicians., Methods: REGIMS, the data source of this study, is a prospective registry investigating the long-term drug safety in the treatment of MS in Germany. Patients included had to meet the revised McDonald criteria (2005) and be treated with immunotherapy. Concordance of adverse events documented six and 12 months after baseline presentation in 642 MS patients from 46 different neurologic outpatient centres all over Germany was analysed. Physicians' documentation was done either on paper or electronically during routine visits, while patients' self-reports were based on mailed questionnaires. Regression models were used to analyse factors influencing reporting., Results: During one year of follow-up patients reported a total number of 4,841 events per 1,000 patient-years (PYs) while physicians reported 467 events/1,000 PYs. Patients' and physicians' reports focused on different body functions and categories, respectively. Factors increasing patients' likeliness to report were female gender (ß-coefficient: 1.52, 95% CI: 0.96-2.09), a history of smoking (ß: 0.80, 95% CI: 0.13-1.47), a higher EDSS score (ß: 0.28, 95% CI: 0.10-0.46) and previous MS therapies (ß: 0.35, 95% CI: 0.11-0.59) increased the patients' reporting of AEs. Physicians were more likely to report an AE for Fingolimod than for Interferon beta preparations (OR = 3.22, 95% CI: 1.22-8.52)., Discussion: Underreporting of adverse events has been a known problem in clinical routine for several years without signs of substantial improvement. Encouraging patients' involvement in adverse event reporting offers the possibility to a more holistic approach to pharmacovigilance. Further investigations in patients' and physicians' strategies when it comes to causality assessment of adverse events related to MS medication may be insightful., (Copyright © 2022. Published by Elsevier B.V.)

The treatment of multiple sclerosis (MS), the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS), continues to transform. In recent years, a number of novel and increasingly effective disease-modulatory therapies (DMTs) have been approved, including oral fumarates and selective sphingosine 1-phosphate modulators, as well as cell-depleting therapies such as cladribine, anti-CD20 and anti-CD52 monoclonals. Amongst DMTs in clinical development, inhibitors of Bruton's tyrosine kinase represent an entirely new emerging drug class in MS, with three different drugs entering phase III trials. However, important remaining fields of improvement comprise tracking of long-term benefit-risk with existing DMTs and exploration of novel treatment targets relating to brain inherent disease processes underlying the progressive neurodegenerative aspect of MS, which accumulating evidence suggests start already early in the disease process. The aim here is to review current therapeutic options in relation to an improved understanding of the immunopathogenesis of MS, also highlighting examples where controlled trials have not generated the desired results. An additional aim is to review emerging therapies undergoing clinical development, including agents that interfere with disease processes believed to be important for neurodegeneration or aiming to enhance reparative responses. Notably, early trials now have shown initial evidence of enhanced remyelination both with small molecule compounds and biologicals. Finally, accumulating evidence from clinical trials and post-marketing real-world patient populations, which underscore the importance of early high effective therapy whilst maintaining acceptable tolerability, is discussed., (© 2020 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background and Aims: Interferon beta (IFNβ) is a well-established first-line therapy for relapsing-remitting multiple sclerosis (RRMS) patients and remains the most widely prescribed agent. Atypical hemolytic uremic syndrome (aHUS) represents a rare but severe adverse effect (AE) that could occur even after many years from the beginning of IFNβ therapy. Eculizumab is currently approved for treatment of aHUS and recently for neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibodies (AQP4-IgG). In this article, we report the case of the latest onset of IFNβ-related aHUS experienced by an MS patient and we briefly review the literature on this topic., Methods: We performed a systematic review of the literature using PubMed, and we performed a retrospective analysis of RRMS patients that received IFNβ-1a in our center and developed thrombotic microangiopathy (TMA). From this search, we identified only one patient., Results: In the published literature, we identified 24 MS patients who received IFNβ as disease-modifying treatment (DMT) and then developed thrombotic microangiopathy with kidney injury. The aHUS has been diagnosed in 6, all received IFNβ-1a and the latest onset was after 15 years. We report a case of a 39-year-old man affected by RRMS who assumed IFNβ-1a since 1999. In July 2018, he developed an IFNβ-related aHUS. After the failure of plasma exchange, he underwent eculizumab, with an improvement of glomerular filtration rate and without new signs of MS activity., Conclusion: To our knowledge, this case represents the latest onset of IFNβ-related aHUS in MS patients. Up to now, there are not literary reports about the possibility to reintroduce a DMT as add-on therapy to eculizumab., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

This paper reviews currently available data on the novel coronavirus and clinical features of COVID-19, followed by a detailed section on possible modifications of immunomodulatory therapy in multiple sclerosis patients with COVID-19, based on what we know so far. There are discussed: (i) The COVID-19 disease (Epidemiological background SARS-CoV-1 coronavirus; Autoimmune response to COVID-19; Asymptomatic course; SARS-CoV-2 test; COVID-19 symptoms), (ii) Treatment of COVID-19 (Experimental plasma treatment; Antiviral therapy; Antimalarial treatment scheme; Biological treatment; Corticosteroid treatment; Symptomatic treatment; Vaccine preparation) and (iii) Multiple sclerosis and SARS-CoV-2 infection (Epidemiological recommendation).

Background: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort., Methods: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab., Results: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076)., Conclusion: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age., Competing Interests: Deckaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Poor adherence to the disease-modifying therapies (DMTs) for multiple sclerosis (MS) may attenuate clinical benefit. A better understanding of characteristics associated with non-adherence could improve outcomes., Objective: To evaluate characteristics associated with non-adherence to injectable DMTs., Methods: Consecutive patients from four Canadian MS Clinics were assessed at three time points over two years. Clinical and demographic information included self-reported DMT use, missed doses in the previous 30 days, health behaviors, and comorbidities. Non-adherence was defined as <80% of expected doses taken. We employed generalized estimating equations to examine characteristics associated with non-adherence at all time points with findings reported as adjusted odds ratios (OR)., Results: In all, 485 participants reported use of an injectable DMT, of whom 107 (22.1%) were non-adherent over the study period. Non-adherence was associated with a lower Expanded Disability Status Scale score (0-2.5 vs 3.0-5.5, OR: 1.80; 95% confidence interval (CI): 1.06-3.04), disease duration (⩽5 vs <5 years, OR: 2.23; 95% CI: 1.10-4.52), alcohol dependence (OR: 2.14; 95% CI: 1.23-3.75), and self-reported cognitive difficulties, measured by the Health Utilities Index-3 (OR: 1.55; 95% CI: 1.08-2.22)., Conclusions: Nearly one-quarter of participants were non-adherent during the study. Alcohol dependence, perceived cognitive difficulties, longer disease duration, and mild disability status were associated with non-adherence. These characteristics may help healthcare professionals identify patients at greatest risk of poor adherence.

Introduction: Multiple sclerosis (MS) is a autoimmune disorder which preferentially affects young women of childbearing age. During pregnancy, the annualized relapse rate (AAR) is modified, but pregnancy has no harm effect on the long-term course of the disease. We aimed to study the clinical course of our MS patients during pregnancy, and compare their obstetrics outcomes with a control group of non-MS patients., Methods: A single centre prospective observational study was conducted. We assessed the reproductive history, MS history, pregnancy course and new-born outcome of a cohort of MS patients who had had a pregnancy between january 2007 and july 2012. We compared the global outcomes with a control cohort of 58 age-matched healthy pregnancies., Results: Complete data from 35 consecutive women were analyzed, 40 deliveries. Control groups: 58 patients, 60 deliveries. EDSS at pregnancy 0,7. ARR before pregnancy 0,5. During pregnancy 0,3, after pregnancy 0,4. Twelve patients were on disease-modifying drugs (DMD) before pregnancy, 4 prenatal exposure occurs. The comparison between relapse rate and EDSS before, during and after delivery showed no statistically significant difference. In addition, compared to control group, there were also no differences in the obstetric outcomes. In MS cohort, we found a higher incidence of assisted reproductive treatments and lower breastfeeding rate, both statistically significant., Conclusions: Our series confirms that pregnancy has no negative long term impact on the progression of MS and also suggest that there is no additional morbidity in the pregnancy, comparing to the rest of the population., (Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Regulatory T cells (Tregs) are functionally defective in patients with multiple sclerosis (MS) and this dysfunction is related to an imbalanced composition of naïve and memory Treg subtypes. Several lines of evidence indicate that these abnormalities might result from a premature decline in thymic-dependent Treg neogenesis. Myeloid dendritic cells (mDCs) critically determine Treg differentiation in the thymus, and thymic stromal lymphopoietin receptor (TSLPR) expressed on mDCs is a key component of the signaling pathways involved in this process. TSLPR-expression on mDCs was previously shown to be decreased in MS. We hypothesized that functional alterations in mDCs contribute to aberrant Treg neogenesis and, in turn, to altered Treg homeostasis and function in MS., Methods: We recruited blood samples from 20 MS patients and 20 healthy controls to assess TSLPR expression on mDCs ex vivo by flow cytometry and by activating mDCs induced by recombinant TSLP (rhTSLP) in vitro. As previous studies documented normalization of both function and homeostasis of Tregs under immunomodulatory (IM) therapy with interferon-beta (IFN-beta) and glatiramer acetate (GA), we also tested phenotypes and function of mDCs obtained from IM-treated patients (IFN-beta: n=20, GA: n=20)., Results: We found that TSLP-induced mDC activation and effector function in vitro was reduced in MS and correlated with TSLPR-expression levels on mDCs. IM treatment prompted upregulation of TSLPR on mDCs and an increase in TSLP-induced activation of mDCs together with a normalization of Treg homeostasis., Conclusion: The decreased TSLP-induced activation of MS-derived mDCs in vitro, together with the reduced density of TSLPR on the cell surface of mDCs corroborates the hypothesis of mDCs being critically involved in impairing Treg development in MS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Natalizumab (NAT) was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis. Its considerable and sustained efficacy has been demonstrated in two phase III studies. However, there are several reasons why its use is limited in clinical practice. The main argument for stopping use of the drug is the risk of the rare but serious progressive multifocal leukencephalopathy. Other reasons are neutralizing antibodies and pregnancy. There is compelling evidence from some clinical trials and many case series that disease activity returns upon suspension or cessation of NAT. Several therapeutic strategies that have been tested to prevent or reduce the recurrence of disease activity will be reviewed in this article. Considering these data, it is evident that the decision to stop NAT treatment has different implications and consequences. A subsequent therapy after cessation of NAT is needed to reduce the risk of disease recurrence.

Multiple sclerosis (MS) is a typical CD4 T cell-mediated autoimmune disease of the central nervous system (CNS) that leads to inflammation, demyelination, axonal damage, glial scarring and a broad range of neurological deficits. While disease-modifying drugs with a good safety profile and moderate efficacy have been available for 20 years now, a growing number of substances with superior therapeutic efficacy have recently been introduced or are in late stage clinical testing. Daclizumab, a humanized neutralizing monoclonal antibody against the α-chain of the Interleukin-2 receptor (IL-2Rα, CD25), which had originally been developed and approved to prevent rejection after allograft renal transplantation, belongs to the latter group. Clinical efficacy and safety of daclizumab in MS has so far been tested in several smaller phase II trials and recently two large phase II trials (combined 912 patients), and has shown efficacy regarding reduction of clinical disease activity as well as CNS inflammation. A phase III clinical trial is ongoing till March 2014 (DECIDE study, comparison with interferon (IFN) β-1a in RRMS). Furthermore, the existing safety data from clinical experience in kidney transplantation and in MS appears favorable. Apart from the promising clinical data mechanistic studies along the trials have provided interesting novel insights not only about the mechanisms of daclizumab treatment, but in general about the biology of IL-2 and IL-2 receptor interactions in the human immune system. Besides blockade of recently activated CD25(+) T cells daclizumab appears to act through additional mechanisms including the expansion of immune regulatory CD56(bright) natural killer (NK) cells, the blockade of cross-presentation of IL-2 by dendritic cells (DC) to T cells, and the reduction of lymphoid tissue inducer cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Evolving data have shown that the toll like receptors (TLRs) family of innate immune receptors has an important role in driving the activation and inhibition of pathogenic pathways involved in multiple sclerosis (MS). While developing clinical trials targeting MS by TLRs modulators are of considerable interest, several of them have failed. Herein, the various consequences of TLRs pathways activation and the potential of targeting these receptors for therapeutic purposes are described. In particular, different aspects of TLR based therapies are discussed, in order to develop more efficacious and safe therapies targeting inflammatory and autoimmune diseases, especially MS.

Multiple sclerosis (MS) is primarily an autoimmune disease of the central nervous system, but also encompasses prominent neurodegenerative aspects. A significant proportion of MS patients will develop neurological disability over time and up until recently treatment options have been limited. However, MS treatment is now at a stage of rapid progress, with several new drugs that have reached the market or will be launched in the near future. This provides new opportunities for individualized treatment, but also creates new challenges regarding monitoring of disease activity, long-term safety issues and efficacy, not least in patients with progressive disease., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Objective: Natalizumab (NTZ) is an effective immunomodulator therapy (IMT) employed for multiple sclerosis (MS) therapy. This study aimed to investigate the efficacy and safety of NTZ treatment in MS patients. Materials and Methods: Patients with clinically definite MS who received NTZ treatment were included in the study, and their data were derived from the iMed database. Patient demographics such as age, sex, and disease duration were assessed. The results pertaining to the annual number of attacks, expanded disability status scale (EDSS) results, magnetic resonance data, and no evidence of disease activity-3 (NEDA-3) were obtained. Results: This study included 153 patients (108 female and 43 male). The patients' ages ranged from 21.63 to 67.60 years, with a mean age of 44.50 years. Prior to undergoing NTZ treatment, 54.3% of the patients had received at least two other IMTs. The mean annual number of assaults was 1.19, and the number of attacks in the year prior to treatment ranged from 0 to 6. The mean number of attacks in the first year following treatment was 0.07, 0.13 in the second year, and 0.09 in the third year. The baseline EDSS values of the patients varied between 0 and 5.5, and the mean baseline EDSS value was 3.08. During the initial year of treatment, the patient's mean EDSS value was 2.58, the second year was 2.32, and the third year was 2.34. Recurrence with increased severity of disease activity or rebound development was observed in 14.6% of the patients whose NTZ treatment was terminated for any reason. The NEDA-3 value decreased from 82.8% (n=145) in the first year to 77.3% (n=132) in the second year and 79.0% (n=81) in the third year. Conclusion: Patients received NTZ for three years on average. 14.6% of the patients exhibit a recurrence or rebound of disease activity. Anti-John Cunningham virus antibody was detected in 5% of patients during the course of treatment. Approximately 80% of patient achieved NEDA-3 while receiving NTZ over the three-year period. [ABSTRACT FROM AUTHOR]

Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.

Demyelinating diseases of the central nervous system and multiple sclerosis in particular are a pressing issue for medical community and society as a whole. Deve- lopment and implementation of highly effective specific therapy significantly slow the disease progression and help maintain patients' quality of life and social participation. We analyzed pathogenic mechanisms of multiple sclerosis and other B cell-mediated diseases and reviewed therapeutic options for main disease stages.

Background: Neurological disability associated with multiple sclerosis and immunosuppressive or immunomodulatory therapy which is administered for it may increase the risk of SARS-CoV-2 infection and its morbidity/mortality.In this study, we evaluated the severity of SARS-CoV-2 infection in patients with multiple sclerosis based on their demographic and disease data.Methods: A total of 1361 multiple sclerosis patients from Fars province were interviewed by phone from April 3 to June 20, 2020. Basic demographic data, information about their disease and any symptoms or laboratory results relevant to COVID-19 were gathered.Results: Among the studied patients, 68 ones (5%) were COVID-19 suspected cases and 8 ones (0.58%) were in the confirmed group. Five cases in the confirmed group needed hospitalization. Two patients died while both of them were taking rituximab. The frequency rate of suspected cases with RRMS was 57 (87.7%), followed by 5 (7.7%) PPMS and 2 (3.1%) CIS. In the confirmed group, 25% used corticosteroid drug and 50% were on rituximab; moreover, 62.5% of the confirmed cases had a high disability level and needed assistance to walk. In whole, 36.8% of the suspected and 25% of the confirmed cases were on IFN-β1; eventually, all of them recovered well from COVID-19 infection.Conclusion: In the present study, the rate of developing COVID-19 in multiple sclerosis patients was similar to the general population and most of patients with multiple sclerosis recovered from COVID-19 without referral to a medical specialist.

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p

Multiple sclerosis (MS) is a chronic demyelinating disease of young employable people. Demyelination develops as a result of the autoimmune mechanisms of the damage to nerve fibers, while the neurodegenerative changes in the brain matter begin from the first days of the disease. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. Usually, there are remitting, secondary progressive, and primary progressive MS. The «gold standard» of treatment after the diagnosis of MS is first-line drugs disease-modifying therapies (DMT) of the first line -glatiramer acetate and в—interferons. These drugs have been used for more than 20 years and have proven their effectiveness, safety and good tolerability in long-term continuous observational clinical studies. It is important to note that therapy should be started as early as possible, from the moment of diagnosis, since in most patients, even with a stable clinical picture and no symptoms, the disease progresses. Over time, this can lead to persistent, irreversible neurological deficits and disability. The use of active immune -modulating drugs requires constant monitoring of the patient’s condition by qualified neurologists. This article presents the results of clinical trials of Timexon® (glatiramer acetate) and Teberif ® (interferon beta- 1а) in patients with remitting multiple sclerosis and discusses the issues of prescribing first-line drugs, switching from one therapy to another within the first-line, monitoring the effectiveness and safety of treatment.

This paper reviews currently available data on the novel coronavirus and clinical features of COVID-19, followed by a detailed section on possible modifications of immunomodulatory therapy in multiple sclerosis patients with COVID-19, based on what we know so far. There are discussed: (i) The COVID-19 disease (Epidemiological background SARS-CoV-1 coronavirus; Autoimmune response to COVID-19; Asymptomatic course; SARS-CoV-2 test; COVID-19 symptoms), (ii) Treatment of COVID-19 (Experimental plasma treatment; Antiviral therapy; Antimalarial treatment scheme; Biological treatment; Corticosteroid treatment; Symptomatic treatment; Vaccine preparation) and (iii) Multiple sclerosis and SARS-CoV-2 infection (Epidemiological recommendation).

Multiple sclerosis (MS) ranks first for prevalence among diseases affecting the CNS white matter with 2.5 million cases estimated globally. InRussia, the number of cases is about 200 thousand. MS in most cases has a wavy course (periods of exacerbations and remissions), over time the progression of disease worses the quality of life of patients. The “gold standard” at the beginning of MS is first-line drugs disease-modifying therapies (DMT). If they are ineffective, it is necessary to strengthen the effect on the immune processes and the patient is prescribed second-line drugs (escalation of therapy). There is a method of induction therapy, when high activity of MS is recommended to start with drugs that have a strong immunosuppressive effect with a possible subsequent transition to soft supportive treatment. In patients with frequent exacerbations and signs of radiological activity of the disease, according to magnetic resonance imaging (MRI) of the brain and spinal cord, monoclonal antibody preparations are effectively used. Except of escalation and induction, it is also used the method of immune system reconstruction, which leads to a decrease in autoagression in MS. This article discusses a clinical case of using a drug of monoclonal antibodies that selectively bind to CD 52 on the surface of lymphocytes. The issues of efficacy and safety of alemtuzumab therapy in patients with MS are considered.

Background: Neurological disability associated with multiple sclerosis and immunosuppressive or immunomodulatory therapy which is administered for it may increase the risk of SARS-CoV-2 infection and its morbidity/mortality. In this study, we evaluated the severity of SARS-CoV-2 infection in patients with multiple sclerosis based on their demographic and disease data. Methods: A total of 1361 multiple sclerosis patients from Fars province were interviewed by phone from April 3 to June 20, 2020. Basic demographic data, information about their disease and any symptoms or laboratory results relevant to COVID-19 were gathered. Results: Among the studied patients, 68 ones (5%) were COVID-19 suspected cases and 8 ones (0.58%) were in the confirmed group. Five cases in the confirmed group needed hospitalization. Two patients died while both of them were taking rituximab. The frequency rate of suspected cases with RRMS was 57 (87.7%), followed by 5 (7.7%) PPMS and 2 (3.1%) CIS. In the confirmed group, 25% used corticosteroid drug and 50% were on rituximab; moreover, 62.5% of the confirmed cases had a high disability level and needed assistance to walk. In whole, 36.8% of the suspected and 25% of the confirmed cases were on IFN-β1; eventually, all of them recovered well from COVID-19 infection. Conclusion: In the present study, the rate of developing COVID-19 in multiple sclerosis patients was similar to the general population and most of patients with multiple sclerosis recovered from COVID-19 without referral to a medical specialist. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Interferon beta (IFNβ) is a well‐established first‐line therapy for relapsing–remitting multiple sclerosis (RRMS) patients and remains the most widely prescribed agent. Atypical hemolytic uremic syndrome (aHUS) represents a rare but severe adverse effect (AE) that could occur even after many years from the beginning of IFNβ therapy. Eculizumab is currently approved for treatment of aHUS and recently for neuromyelitis optica spectrum disorder (NMOSD) with aquaporin‐4 antibodies (AQP4‐IgG). In this article, we report the case of the latest onset of IFNβ‐related aHUS experienced by an MS patient and we briefly review the literature on this topic. Methods We performed a systematic review of the literature using PubMed, and we performed a retrospective analysis of RRMS patients that received IFNβ‐1a in our center and developed thrombotic microangiopathy (TMA). From this search, we identified only one patient. Results In the published literature, we identified 24 MS patients who received IFNβ as disease‐modifying treatment (DMT) and then developed thrombotic microangiopathy with kidney injury. The aHUS has been diagnosed in 6, all received IFNβ‐1a and the latest onset was after 15 years. We report a case of a 39‐year‐old man affected by RRMS who assumed IFNβ‐1a since 1999. In July 2018, he developed an IFNβ‐related aHUS. After the failure of plasma exchange, he underwent eculizumab, with an improvement of glomerular filtration rate and without new signs of MS activity. Conclusion To our knowledge, this case represents the latest onset of IFNβ‐related aHUS in MS patients. Up to now, there are not literary reports about the possibility to reintroduce a DMT as add‐on therapy to eculizumab.

Copyright of Current Neurology / Aktualno?ci Neurologiczne is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper reviews currently available data on the novel coronavirus and clinical features of COVID-19, followed by a detailed section on possible modifications of immunomodulatory therapy in multiple sclerosis patients with COVID-19, based on what we know so far. There are discussed: (i) The COVID-19 disease (Epidemiological background SARS-CoV-1 coronavirus; Autoimmune response to COVID-19; Asymptomatic course; SARS-CoV-2 test; COVID-19 symptoms), (ii) Treatment of COVID-19 (Experimental plasma treatment; Antiviral therapy; Antimalarial treatment scheme; Biological treatment; Corticosteroid treatment; Symptomatic treatment; Vaccine preparation) and (iii) Multiple sclerosis and SARSCoV- 2 infection (Epidemiological recommendation). [ABSTRACT FROM AUTHOR]

Copyright of Current Neurology / Aktualno?ci Neurologiczne is the property of Medical Communications Sp. z o.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

V Limmroth,1 J Reischl,2 B Mann,3 X Morosov,2 A Kokoschka,2 I Weller,2 T Schreiner2 1Clinic for Neurology and Palliative Medicine, Municipal Hospital Köln-Merheim, Cologne, 2Bayer Vital GmbH, Leverkusen, 3IFAK Institute GmbH & Co. KG, Taunusstein, Germany Purpose: Autoinjectors are well-established in supporting multiple sclerosis (MS) therapy. This market survey was aimed at investigating patients’ rating of three devices for subcutaneous interferon beta formulations: the electronic autoinjectors Betaconnect® and RebiSmart™ as well as the mechanical ExtaviPro™ device. Patients and methods: Organization and conduction of structured face-to-face interviews in five German cities were managed through an independent external market research company. After questionnaire validation (n=15), 85 participants currently either using the Betaconnect (n=39), the RebiSmart (n=36) or the ExtaviPro injector (n=10) were asked 22 questions in the same order. First, patients named their current device in use, watched the corresponding instruction video, and were queried about their device. Second, patients were asked about their opinion of an ideal autoinjector. Third, instruction videos for the two non-used devices were presented and participants could dummy-inject into a pillow. Last, patients evaluated device features and indicated their preferred autoinjector. Results: Before having been presented the two other autoinjectors not in use, evaluation of patients’ satisfaction with their own device revealed that 82% of the Betaconnect users, 67% of the RebiSmart and 60% of the ExtaviPro users were highly satisfied. All patients desired some improvement of their own device particularly concerning optimization of size and handling. Subsequent to testing and watching instruction videos of all devices, the Betaconnect received the best rating regarding different functions. Finally, participants indicated their preferred autoinjector, provided their own medication was suitable for all three devices: 56.5% of the participants (n=48/85) chose the Betaconnect, 36.5% the RebiSmart (n=31/85), and 5% the ExtaviPro device (n=4/85); 2% did not answer (n=2/85). Conclusion: In this survey, the Betaconnect device was the preferred autoinjector and may currently best meet patients’ needs. As it was closest to participants’ opinion of an ideal device, the Betaconnect might contribute to treatment adherence. Our results need to be confirmed in further studies. Keywords: adherence, multiple sclerosis, immunomodulatory therapy, electronic autoinjector, market survey

Multiple sclerosis (SM) is an incurable, advancing, demyelinating illness with inflammatory background. It constitutes the most frequent cause of disability among young people, between 20 and 40 years of age. Despite the identification of multiple factors causing the disease, its pathomechanism has not been yet completely discovered. For this reason, finding an effective cure for multiple sclerosis continues to present a challenge (for modern scientists). The currently available treatment for SM aims to halt its progress and to minimalize complications related to the disease. The goal of the work was to provide an overview of the therapies currently available to those suffering from SM. Selecting an appropriate form of treatment and medication as well as preparing the patient and continuation of monitoring during the therapy constitute important elements of conducting an effective SM therapy. (JNNN 2015;4(3):130–137)

Clinically effective immunomodulatory therapies have been developed for relapsing-remitting multiple sclerosis (RRMS), but they have generally not translated to a corresponding slowing of disability accumulation in progressive forms of multiple sclerosis (MS). Since disability is multifaceted, progressive patients are heterogeneous, and the drivers of disease progression are still unclear, it has been difficult to identify the most informative outcome measures for progressive trials. Historically, secondary outcome measures have focused on inflammatory measures, which contributed to the recent identification of immunomodulatory therapies benefiting younger patients with more inflammatory progressive MS. Meanwhile, agents capable of treating late-stage disease have remained elusive. Consequently, measures of neurodegeneration are becoming common. Here, we review completed clinical trials testing immunomodulatory therapies in primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS) and discuss the features contributing to trial design variability in relation to trial outcomes, and how efforts toward better patient stratification and inclusion of reliable progression markers could improve outcomes. [ABSTRACT FROM AUTHOR]

So far little has been known about antioxidant properties of immunomodulatory drugs. The aim of the study was to evaluate the antioxidant status in serum of relapsing-remitting multiple sclerosis (RRMS) patients treated with II-line immunomodulatory therapy compared to de novo diagnosed patients, subjects treated with interferon (IFN) beta and healthy controls. We analyzed the relationships depending on the gender, age, disease duration, the Expanded Disability Status Scale, the annualised relapse rate, and MRI lesions in patients treated with II-line. One hundred and twenty one RRMS patients were enrolled in the prospective study. Patients were divided into the following groups: de novo, IFN, fingolimod (FG), natalizumab (NT), and the control. The total antioxidant capacity, sulfhydryl groups (SH groups, PSH groups), ceruloplasmin, and superoxide dismutase (SOD) activity were determined in serum. NT and FG groups presented with lower SOD activity compared to controls. The levels of antioxidants in NT- and FG-treated patients were not different from the IFN group. Antioxidant parameters increased with disease duration in the FG group. FG and NT could have an effect on the antioxidant system in multiple sclerosis (MS) patients. The results of this study propose a novel aspect of antioxidative properties of II-line immunomodulatory therapy in MS. [ABSTRACT FROM AUTHOR]

Background: Poor adherence to the disease-modifying therapies (DMTs) for multiple sclerosis (MS) may attenuate clinical benefit. A better understanding of characteristics associated with non-adherence could improve outcomes. Objective: To evaluate characteristics associated with non-adherence to injectable DMTs. Methods: Consecutive patients from four Canadian MS Clinics were assessed at three time points over two years. Clinical and demographic information included self-reported DMT use, missed doses in the previous 30 days, health behaviors, and comorbidities. Non-adherence was defined as <80% of expected doses taken. We employed generalized estimating equations to examine characteristics associated with non-adherence at all time points with findings reported as adjusted odds ratios (OR). Results: In all, 485 participants reported use of an injectable DMT, of whom 107 (22.1%) were non-adherent over the study period. Non-adherence was associated with a lower Expanded Disability Status Scale score (0-2.5 vs 3.0-5.5, OR: 1.80; 95% confidence interval (CI): 1.06-3.04), disease duration (≥5 vs <5 years, OR: 2.23; 95% CI: 1.10-4.52), alcohol dependence (OR: 2.14; 95% CI: 1.23-3.75), and self-reported cognitive difficulties, measured by the Health Utilities Index-3 (OR: 1.55; 95% CI: 1.08-2.22). Conclusions: Nearly one-quarter of participants were non-adherent during the study. Alcohol dependence, perceived cognitive difficulties, longer disease duration, and mild disability status were associated with non-adherence. These characteristics may help healthcare professionals identify patients at greatest risk of poor adherence. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Glatiramer acetate (GA) has been shown to reduce the number of relapses and improve outcomes in relapsing-remitting multiple sclerosis (RRMS) patients. The aim of this study is to investigate the efficacy and side effects of GA in RRMS patients treated with it. METHODS: We retrospectively reviewed all the records of RRMS patients treated with GA in our hospital from January 1990 to December 2010. We evaluated 114 records but 71 patients (48 women, 23 men) were included in the study due to incompleteness in the other records. Demographic characteristics, time from first symptom to diagnosis, time from diagnosis to treatment, number of relapses and Expanded Disability Status Scale (EDSS) scores before and after the treatment, treatment duration, side effects, the other agents used in MS treatment during the disease duration and the presence of oligoclonal bands were recorded. RESULTS: The mean age of the patients and mean GA treatment duration were 41,85±9,05 years and 28,73 months, respectively. The mean number of relapses before and after the treatment were 2.30±1.16 and 0,52±1.24 respectively. The number of relapses reduced in 64 (90,14%), unchanged in 4 (5,63%) and increased in 3 (4,23%) patients after GA treatment. The mean EDSS scores before and after the treatment were 2,56±1,46 and 2,04±1,68 respectively. Before GA treatment, 63,4% of all patients had EDSS scores three or more. After the treatment 50,6% of all patients had EDSS scores three or more. GA was the first choice immunomodulatory treatment in 71,8% and the second choice in 28,2% of the patients. The treatment discontinued in 8 (11,3%) patients and the reason was the severe side effect in only one patient (1,4%). CONCLUSION: Glatiramer acetate decreased the number of relapses and EDSS score with tolerable side effects.

The efficacies of immunosuppressive (IMS) and immunomodulatory (IMM) drugs for multiple sclerosis (MS) have been reported in several studies. These agents can reduce relapse rates and lesions observed by magnetic resonance imaging studies. However, the effect of these medications in disability progression over 4 years is rarely examined. OBJECTIVE: To study the disabilities associated with MS patients after a long time period and to analyze the therapeutic influence of different types of treatments in patient disease progression. METHOD: This is an open, uncontrolled, non-randomized, retrospective study of the disease progression using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) in 155 cases of MS, which were 76% female with a mean age of onset of 30.21±9.70. The follow-up period was 115.39±88.08 months (median 92, 3 to 447 months). These cases were submitted to the following 277 different therapeutic procedures: 62 without IMS or IMM therapy (SYT) (just corticosteroids), 53 with azathioprine (AZA), 53 interferon-β (IFNβ)-1b 250 µg (BET), 55 IFNβ-1a 22 µg (R22), 19 IFNβ-1a 30 µg (AVO), 15 IFNβ-1a 44 µg (R44), 15 glatiramer acetate (COP) 20 mg, and 5 cases with mitoxantrone (MIT). RESULTS: The median EDSS group was 2.00 (0 to 5.5, mean 1.89±1.52) at the onset of each treatment and 2.50 (0 to 9, mean 3.06±2.18) at the end. The median initial MSSS was 3.34 (0.25 to 9.50, mean 3.94±2.91) and the final medial was 3.90 (0.05 to 9.88, mean 4.02±2.78). The EDSS between initial and final score for the whole group had statistically significant progression, as well as for the sub-groups SYT, AZA, BET and R22. No statistically significance difference was found in the MSSS between initial and final scores in the whole group or treatment sub-groups. The variation between the initial and final EDSS and MSSS among the types of treatments found no statistical significance for any group. CONCLUSION: In this study series, no statistical difference was found in the long-term progression of disability among the IMS and IMM treated cases, nor in the cases treated only with corticosteroids.A eficácia das medicações imunossupressivas (IMS) e imunomoduladoras (IMM) na esclerose múltipla (MS) tem sido relatada em diversos estudos. Essas medicações podem reduzir o número de surtos e de lesões observadas nos estudos de ressonância magnética. Entretanto, o efeito dessas medicações na progressão da incapacidade em período acima de quatro anos é raramente estudado. OBJETIVO: Estudar a incapacidade associada à MS em longo prazo e analisar os benefícios dos diferentes tipos de tratamento na progressão da doença. MÉTODO: Estudo aberto e retrospectivo da progressão da incapacidade utilizando a escala expandida do grau de incapacidade (EDSS) e o escore da gravidade da esclerose múltipla (MSSS) em 155 casos de MS, sendo 76% do sexo feminino, idade média no início da doença 30,21±9,70 anos e período médio de seguimento 115,39±77,08, mediana 92 (3 a 447) meses. Os casos foram submetidos a 277 tipos diferentes de tratamentos: 62 casos não usaram IMS ou IMM, somente corticosteróides (SYT); 53 com azatioprina (AZA); 53 com interferon-β (IFNβ)-1b 250 µg (BET); 55 com IFNβ-1a 22 µg (R22); 19 com IFNβ-1a 30 µg (AVO); 15 com IFNβ-1a 44 µg (R44); 15 com acetato de glatiramer (COP) 20 mg, e 5 casos com mitoxantrone (MIT). RESULTADOS: A mediana do EDSS do grupo foi 2,0 (0 a 5,5, média total do grupo foi 1,89±1,52) no início de cada tratamento e 2,50 (0 a 9, média de 3,06±2,18) no fim. A mediana inicial da MSSS foi 3,34 (0,25 a 9,50, média 3,94±2,91) e a final 3,90 (0,05 a 9,88, média 4,02±2,78). O EDSS entre o início e o fim do tratamento do grupo mostrou progressão estatisticamente significante e também para os subgrupos SYT, AZA, BET e R22. Não foi encontrada diferença estatística no MSSS entre o início e fim do tratamento no grupo total ou nos subgrupos. Não foi encontrada diferença estatisticamente significante entre a variação inicial e final do EDSS e MSSS entre os diversos subgrupos de tratamento. CONCLUSÃO: Nesta série, não foi encontrada diferença estatística na progressão da incapacidade em longo prazo entre os IMS e IMM, bem como nos casos tratados unicamente com corticosteróides.

The human polyomavirus JC PyV lytic infection of oligodendrocytes in the human brain results in the demyelinating disease progressive multifocal leukoencephalopathy, PML. JCV is a common virus infection in the population that leads to PML in patients with underlying diseases and therapies that cause immune deficiencies or modulate immune system functions. Patients may have high levels of antibody to JCV that does not protect them from PML nor clear the infection once PML is established. Cell mediated immunity plays a more effective role in clearing initial or reactivated JCV infection before PML occurs. However patients with underlying diseases and therapies for treatment are at high risk for PML. MS patients on natalizumab are one of the categories with the highest incidence of PML. Natalizumab is a humanized monoclonal antibody targeting α4 integrins that prevents inflammatory cells from entering the brain and it has been used as a treatment for MS. A number of studies have investigated the occurrence of PML in these patients and their cell mediated immune profile that might gain insight into the mechanism that ties natalizumab with a high risk of developing PML. It seems that cells of the immune system participate in the pathogenesis of PML as well as clearance of JCV infection.

Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoimmune, genetic, and environmental factors play important roles in its development, making it a multifactorial disease. The disease in children almost always presents in the relapsing-remittent form. The therapy involves treatment of relapses, and immunomodulatory and symptomatic treatment. The treatment of children with MS has to be multidisciplinary and include pediatric neurologists, ophthalmologists, psychologists, physiotherapists, and if necessary, pediatric psychiatrists and pharmacologists. The basis of MS therapy should rely on drugs that are able to modify the course of the disease, i.e. immunomodulatory drugs. These drugs can be subdivided into two general categories: first-line immunomodulatory therapy (interferon beta-1a, interferon beta-1b, glatiramer acetate) and second-line immunomodulatory therapy (natalizumab, mitoxantrone, fingolimod, teriflunomide, azathioprine, rituximab, dimethyl fumarate, daclizumab). Treatment of relapses involves the use of high intravenous doses of corticosteroids, administration of intravenous immunoglobulins, and plasmapheresis. We summarize here the current available information related to the etiology and treatment options in MS. Early administration of immunomodulatory therapy is beneficial in adults, while more studies are needed to prove their effectiveness in pediatric populations. Therefore, pediatric MS still represents a great challenge for both, the early and correct diagnosis, as well as its treatment. [ABSTRACT FROM AUTHOR]

Background The common symptoms of multiple sclerosis are fatigue, depression, cognitive dysfunction, pain and sexual dysfunction, which influence the health-related quality of life of the patients. Objective We aimed to determine the correlations between the health-related quality of life, the level of disability, fatigue and depression in glatiramer acetate-treated patients with multiple sclerosis in Hungary. Methods The Hungarian versions of the Multiple Sclerosis Quality of Life-54, Fatigue Impact Scale and Beck Depression Inventory questionnaires were completed by 428 relapsing-remitting multiple sclerosis patients treated with glatiramer acetate from 19 Hungarian centers. Results The prevalence of fatigue was found to be 62.4%. The prevalence of depression was lower (13.4%) than that described in previous studies (36–54%) among patients with multiple sclerosis. Significant differences in the health-related quality of life were found between fatigued and non-fatigued patients. The level of disability, fatigue, depression and the duration of the disease correlated significantly with the quality of life. However, linear regression analysis indicated that the quality of life was predicted by the level of disability, depression, social and cognitive fatigue, but not by physical fatigue. Conclusions Decreasing the disease activity in multiple sclerosis with immunomodulatory therapy, together with improvements of the diagnostics and treatment of the accompanying depression and fatigue are of high priority to improve the health-related quality of life of patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-β administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-β treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or -non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-β in naïve MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-β treatment are more likely to be non-responders to this therapy. [ABSTRACT FROM AUTHOR]

Since 1993 the Federal Drug Administration approved the use of immunomodulatory therapy in multiple sclerosis (MS), modifying the natural course of disease, as demonstrate our experience in treatment of MS patients at the MS Treatment Center (CATEM). OBJECTIVE: To evaluate patient behavior using immunomodulatory therapy for a period of five years treatment. METHOD: We selected 390 patients in CATEM with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. RESULTS: At initial treatment 292 (61.5%) patients presented RRMS, 98 (20.6%) SPMS with relapses, 27 SPMS (5.6%) and 58 (12.1%) primary progressive MS (PPMS). In RRMS 182 (62.5%) used the interferon beta 1a SC, 15 (5.2%) interferon beta 1a IM, 85 (29%) interferon beta 1b and 10 (3.3%) glatiramer acetate. In SPMS 63 (64.3%) used interferon beta 1a SC, 4 (4.1%) interferon beta 1a IM and 31 (31.4%) interferon beta 1b. We observed that in this period 195 (50%) migrated between drugs, 35 (9%) gave up therapy and 160 (41%) continued the initial therapy. CONCLUSION: Stopping the immunomodulatory therapy emerges as a problem in the second year of treatment and it can be a subset of interferon non responsive or development of neutralizing antibodies.

A clinically isolated syndrome (CIS) is a term which describes the first clinical onset of a potential multiple sclerosis (MS). It ought to be defined as an MS stage rather than a separate disease entity; however, with respect to the diagnostic work-up, differential diagnoses to be considered, prognostic factors for the development of a clinically confirmed MS and initiation of an immunomodulatory therapy, there are some important considerations supported by recent studies. These considerations as well as the current guidelines are critically discussed in this review article. Additionally, recommendations are given regarding the management of radiologically isolated syndrome (RIS) an imaging-based diagnosis of a potential preclinical stage of MS. [ABSTRACT FROM AUTHOR]

Background and purpose Isolated optic neuritis ( ON) is frequently the initial symptom of multiple sclerosis ( MS). The aim of our study was to investigate the risk of conversion to MS in children following isolated ON and to evaluate the performance of current diagnostic methods such as cranial magnetic resonance imaging ( cMRI), visual evoked potentials ( VEPs) and oligoclonal bands in spinal fluid ( OCB) as predictive factors for MS development. Methods Medical records of 159 patients presenting with acute ON between 2000 and 2010 at the Department of Pediatrics, University of Erlangen, were screened; 34 patients with isolated ON were identified. Progression to MS was defined according to the revised Mc Donald criteria 2005. Age, sex, VEPs, ON type, cMRI, OCB and visual recovery were assessed as predictors of progression to MS using simple logistic regressions. A multiple logistic regression model included variables found to be significant in univariate analyses. Results Abnormal cMRI was associated with an increase in the odds of MS development (odds ratio 20.57; 95% CI 2.16-196.10, P < 0.001), as was positive OCB (odds ratio 12.0; 95% CI 1.29-111.32, P = 0.001). However, only cMRI remained statistically significant in multiple regressions. Conclusions Multiple sclerosis-like cMRI lesions and OCB are suitable for assessing the risk of progression to MS following isolated ON, as children with both cMRI abnormalities and positive OCB at onset of ON are at high risk of developing MS. [ABSTRACT FROM AUTHOR]

Adherence to an immunomodulatory therapy still needs to be improved in MS patients. We analyzed the data of 396 MS patients of 40 German MS outpatient centers who had stopped an ongoing immunomodulatory treatment. Items analyzed were among others adherence data, reasons for the interruption and willingness to start a new therapy. It became obvious that 74.6 % of the patients made the decision to withdraw from therapy on their own. The most commonly mentioned reasons for the withdrawal were proven or putative lack of efficacy (51.4 %), side effects (58.1 %), and complaints of fatigue and depression. There was no difference concerning sex, duration of the treatment and medication taken. The expectations correlated with the empathy of the treating physician and the setting with MS nurses taking care of the patient. A total of 199 patients (51.8 % of the females, 48.9 % of the males) wanted to restart another IMT. Reasons for not wanting to restart were lack of conviction that a therapy may influence the disease (29.4 %), fear of injection (18.7 %), fear of bringing the disease to mind regularly (17.9 %) and doubt about the diagnosis (11.2 %). The results suggest that adherence is most effectively promoted by cultivating an appropriate and individual therapeutic setting for each MS patient on a medical, organizational and last but not least psychological level. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system. Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects. Intramuscular IFN-β 1a and subcutaneous IFN-β 1b are currently available in Japan, but large-scale studies evaluating the prevalence and clinical implications of NAbs against these IFN-β preparations in MS patients have only been performed in Caucasian populations. NAbs positivity has been reported to be associated with HLA-DRB1 alleles, suggesting that the positivity might differ among populations with distinct genetic backgrounds. Clinical information and sera were collected from 229 consecutive MS patients treated with IFN-β in 4 centers in Japan. Sera were tested for NAbs using a luciferase reporter gene assay. In total, 5.2% of IFN-β-1a-treated patients (4/77) and 30.3% of IFN-β-1b-treated patients (46/152) were positive for Nabs. The frequency of NAbs was highest in patients treated for 13 to 24 months. Clinical relapse and contrast-enhancing lesions in the magnetic resonance imaging increased together with NAbs titers in this group. In conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in Caucasian populations and is associated with an increase in disease activity. Therefore, routine NAbs testing is recommended also in Asian populations to ensure the early identification of patients who would benefit from a change in therapy. [ABSTRACT FROM AUTHOR]