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Parkinson's disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons and intraneuronal accumulation of protein aggregates. The exact mechanisms leading to neuronal death in PD are not fully understood, but several different molecular pathways are involved, leading to the concept that molecular subtypes may coexist in the nosological spectrum of PD. To this respect, immune system activation, both in the periphery and inside the central nervous system, was detected as a common trait of several pathogenic pathways of PD. The current working hypothesis implies that immune cells shift towards a proinflammatory phenotype and trigger the production of neurotoxic cytokines, ultimately contributing to neurodegeneration. While it is very important to understand how commonly used antiparkinson drugs interact with such changes, the search for treatments that may directly or indirectly modulate immune function is a great opportunity for disease modification., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background Multiple sclerosis (MS) is an immune-mediated inflammatory disease that attacks myelinated axons in the central nervous system, destroying the myelin and axon to varying degrees and producing significant physical disability. So far, many studies have found that having a high body mass index (BMI) is associated with severe autoimmune and neurodegenerative disease course. However, the impact of BMI on disease-modifying therapy (DMT) response in terms of decreasing relapses and improving overall health remains unknown. Aims and objectives The study aimed to demonstrate the effect of BMI on DMT responsiveness in patients with relapse-remitting MS at a tertiary hospital. Methods and material A single-center retrospective study was conducted at a tertiary care center in Jeddah, Saudi Arabia. The study included 89 individuals with relapsing-remitting MS who had their BMI measured within six months of their first clinical relapse, as well as their clinical response to the DMT (number of relapses on a single DMT after six months of initiation) and MRI changes (development of new T2 lesions or gadolinium-enhancing lesions on single DMT six months after DMT initiation). Results Demographic data revealed a female predominance of 71.9%, and 51.7% of the patients had a normal weight. The most commonly prescribed DMT was Gilenya at 47.2%. A significant relationship was found between BMI and the total number of clinical relapses (p=0.038), with the co-existence of a positive correlation between BMI and the number of relapses after at least six months of initiation of DMT. Additionally, MS patients who had both positive MRI changes and obesity had a significantly higher BMI mean than non-obese. Conclusion Increased BMI appeared to be associated with a lower response to DMT, as overweight patients had a worse course than normal and underweight patients. Pharmacokinetic differences are the most likely factors implicated in medication responsiveness., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Aljehani et al.)

Recent advances in managing Sickle Cell Disease (SCD) significantly improved patient survival and quality of life. Disease-modifying drug therapies such as hydroxyurea, L-glutamine, voxelotor, and crizanlizumab reduce pain crises and severe complications. Allogeneic hematopoietic stem cell transplantation using matched-sibling donors is currently the only standard curative option; however, only a small proportion of patients have such donors. Cord blood and haploidentical transplantation with a modified conditioning regimen have expanded the allogeneic donor pool, making the therapy available to more patients. Gene therapy is a promising cure that is currently undergoing clinical trials and different approaches have demonstrated efficacy. Multidisciplinary expertise is needed in developing the best treatment strategy for patients with SCD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tanhehco, Nathu and Vasovic.)

Osteoarthritis (OA) can be treated using either a pharmacological or non-pharmacological approach, or a combination of both. The purpose of the present study was to investigate the efficacy of crystalline glucosamine sulfate (CGS) in patients with knee OA. This open-label prospective study (with a 12-month follow-up) included 111 patients of both genders suffering from knee OA, who attended the Special Hospital for Rheumatic Diseases in Novi Sad, Serbia during the 2011-2013 period. Patients were divided into the experimental (n=52) and the control (n=59) group. While the former was prescribed CGS 1500 mg/day, the latter was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) according to the standard protocol. The efficacy of both treatment modes was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne index, along with the radiological findings which involved knee joint space width (JSW) measurements. One year following the initial assessment, all patients reported pain intensity reduction; however, those in the CGS group experienced significantly lower pain intensity when compared with controls. At the end of the study, no reduction in the progression of joint structure damage (p>0.5) was noted in either group. Thus, while CGS demonstrated symptomatic efficacy, it failed to delay the progression of knee OA.

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS) that causes significant disability. Immunosuppressive and immunomodulatory drugs have been designed for years to treat MS, as it was considered the most appropriate way to balance the effects of the patients' immune reaction. However, basic and clinical research has recently offered new data that help to better understand the nature of this complex disease, allowing changing the treatment approach. As a consequence, the first disease-modifying drug with a suggested neuroprotective and antioxidative mechanism of action has been recently approved, broadening and improving the therapeutic landscape to fight against MS. In this review, we focused our attention on promising neuroprotective or neuroregenerative drugs that are currently approved or in clinical trials. These neuroprotective therapies provide new valid alternatives that significantly could impact on disease progression and neurodegenerative changes in MS. [ABSTRACT FROM AUTHOR]

Inflammation is among the major determinants of bone loss in chronic disease and aging. Bone metabolism is radically affected by inflammation with consequent bone loss and increased fracture risk. Various cytokines and mediators are involved in the pathogenesis of bone loss in inflammatory conditions. The present review has the aim of discussing the main pathways involved in the pathogenesis of bone loss in inflammatory diseases, focusing in particular on the Wnt system and its regulators. Literature review of studies published between inception to 2021 on osteoporosis and inflammation was conducted. I will discuss the epidemiology of osteoporosis and fractures in common inflammatory diseases. The molecular basis of bone loss related to inflammation will be discussed as well. Finally, the effects of various anti-inflammatory medications on bone metabolism will be reviewed. [ABSTRACT FROM AUTHOR]

Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology. [ABSTRACT FROM AUTHOR]

"Alzheimer's disease (AD) accounts for approximately 70 percent of dementia cases and is characterized by the need for specialized, high cost, long-term care. It is estimated that by the year 2050, AD will affect 13.5 million individuals within the US alone, a prevalence rate representing 10% of that predicted at the global level. As such, AD stands as one of the most important health challenges of the 21st century. While initially viewed as a distinct clinicopathological entity -- with the attendant implications of synonymity between AD pathology and the clinical symptoms of AD -- advances in the neurobiology of AD have led to a revised conceptualization of AD in which the underlying pathophysiology is thought to precede the clinical diagnosis of AD by up to a decade. This has led to a growing consensus that the predementia phase of AD may represent a therapeutic window of opportunity -- a period during which disease modifying drugs may prove effective -- and has resulted in: 1) an increasing shift toward the use of biomarkers -- measures that allow for in vivo detection of AD pathophysiology; and 2) the concept of early disease modifying interventions as a strategy to prevent or delay dementia onset. Collectively, these elements have found expression in the recent revisions to the diagnostic criteria for AD, namely those advanced by the National Institute of Aging and Alzheimer's Association workgroups. While these developments signal progress in the fight against AD, they likewise bring to the fore ethical implications that merit careful consideration. These are the potential impact of a diagnosis of AD in its predementia stages and the implications of the new criteria on practicing physicians, those working in memory clinics, and society as a whole." [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a neurological disease with diverse treatment options, but one of the main tools of maintaining a relatively acceptable life quality is the pharmacological approach through disease modifying therapies. The objective of this paper is to give a brief presentation of the main feasible drug options, a higher attention being offered to glatiramer acetate. [ABSTRACT FROM AUTHOR]

Osteoarthritis is one of the most common forms of musculoskeletal disease and the most prominent type of arthritis encountered in all countries. Although great efforts have been made to investigate cartilage biology and osteoarthritis pathology, the treatment has lagged behind that of other arthritides, as there is a lack of effective disease-modifying therapies. Numerous approaches for dealing with cartilage degradation have been tried, but enjoyed very little success to develop approved OA treatments with not only symptomatic improvement but also structure-modifying effect. In this review we discuss the most recent findings regarding the regulation of cartilage biology and pathology and highlight their potential therapeutic values. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate potential predictors of response to conventional DMARDs in RA. Methods: Study design – 6-month follow-up prospective study. Participants: RA patients with active disease. Intervention and follow-up: Introduction of one DMARD. Response to treatment evaluated at 6 months (ACR20 criteria). Analysis: Potential predictors of response, patients’ demographics, disease activity, percentages of PBMC subsets expressing P-gp, serum IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α levels, were evaluated using univariate and multivariate logistic regression analysis. ROC curve analyses were performed in order to obtain thresholds allowing the prediction of response. Results: Forty-two patients (mean age=57±13 years, mean disease duration=5.4±7.2 years) were included. MTX was given to 30. The response to therapy was predicted by the baseline serum level of TNF-α (mean=30.2 pg/ml±18 in non-responders vs. 11.9 pg/ml±11.2 in responders). The threshold, which predicted with the best accuracy the response to treatment, was 20.1 pg/ml (sensitivity, specificity, positive and negative predictive values of 75, 78.9, 83.3, and 69.2%, respectively; AUC=80.3%, 95% CI=62.8–97.7%). Similar results were obtained in the subgroups of patients treated with MTX and patients with early RA of less than 3 years duration. Conclusion: In the present work, the serum concentration of TNF-α was related to further response to DMARDs. Other works are needed for confirmation and to assess whether such biomarker could be used to predict the response to DMARDs at the individual level. [ABSTRACT FROM AUTHOR]

Objective: The study objective is to compare the annual total medical and indirect costs of newly treated and untreated employees with multiple sclerosis (MS). Research design and methods: A retrospective database analysis of employer medical, drug, and disability claims database (Ingenix Employer database, 1999–2005; 17 large US companies) was conducted for employees 18–64 years of age with ≥1 MS diagnosis after January 1, 2002. Employees with ≥1 MS disease-modifying drug (DMD) claim comprised the newly treated group; employees with MS but no DMD at any time comprised the untreated, comparison group. Index date was the day after the most recent claim (treated, DMD claim; untreated, MS claim) meeting the following requirements: continuous health coverage for 3 months before (baseline period) and 12 months after the index date (study period) and actively employed during baseline. Main outcome measures: Total medical costs and indirect (work loss) costs over the 1-year study period (2006 $US) were compared for DMD-treated and untreated MS employees, adjusting for baseline characteristics, including comorbidities. Results: During the baseline, MS employees who became treated (n = 258) were younger (40.9 vs. 44.4 years, p < 0.0001) and had a higher proportion of women (72 vs. 62%, p = 0.007) than the untreated group of MS employees who never received DMD treatment (n = 322). The 3-month baseline MS-related medical costs were higher among treated MS employees ($2520 vs. $1012, p < 0.0001). There was a nonsignificant trend toward higher baseline non-MS-related medical costs in untreated versus treated MS employees. Risk-adjusted total annual medical costs ($4393 vs. $6187, p < 0.0001) and indirect costs ($2252 vs. $3053, p < 0.0001) were significantly lower for treated MS employees than for untreated MS employees. Conclusions: Initiation of MS disease-modifying drugs was associated with substantial significant medical and indirect savings for employees with MS. Study findings should be considered in the context of the study limitations (e.g., analytic focus on employees with at least 12-month follow-up; lack of clinical detail on MS severity). [ABSTRACT FROM AUTHOR]

• Lymphopenia is a common side effect of treatment with dimethyl fumarate. • Basal absolute lymphocyte count best predicts the development of lymphopenia. • Lymphopenia is not associated with NEDA-3 status. Lymphopenia is a common side effect of treatment with dimethyl fumarate (DMF) in patients with multiple sclerosis (PwMS). Prevalence and predictive factors of this side effect are still uncertain, because literature has provided discrepant results and it is still a matter of debate if lymphopenia is associated with a better treatment outcome. We retrospectively recruited PwMS treated for at least one month with DMF and collected clinical, demographic data and absolute lymphocyte count (ALC) during follow-up. Lymphopenia was graded according to CTCAE. Patients according to the grade in lymphopenia (all grades) and severe lymphopenia (grade II-IV). To evaluate predictors of lymphopenia, we compared characteristics of patients with/without lymphopenia and patients with/without severe lymphopenia. A logistic binary regression was performed to elucidate any predictive factor of lymphopenia and severe lymphopenia. Area under the curve (AUC) was calculated to evaluate sensibility and specificity of predictors. We analyzed treatment outcome with NEDA-3 status at 1- and 2-years. 98 of 105 patients treated with DMF were included. 46.9% developed lymphopenia, 27.6% severe lymphopenia. Lymphopenia was associated with basal ALC (p <0.001, AUC=0.786), treatment duration (p = 0.01, AUC=0.685),% of reduction at third month (p = 0.001, AUC=0.616) Severe lymphopenia was associated with basal ALC (p = 0.003, AUC=0.750).NEDA-3 status at 1-year (n = 66) and at 2-year (n = 44) did not differ in patients with/without lymphopenia (p = 0.059; p = 0.583) or with/without severe lymphopenia (p = 1.02; p = 0.169). Lymphopenia is a common side effect of DMF and basal ALC predicts its development. Lymphopenia is not associated with the achievement of NEDA-3 status. [ABSTRACT FROM AUTHOR]

Abstract: Optic neuritis (ON), a common manifestation of multiple sclerosis (MS), often occurs as the initial manifestation of central nervous system demyelination or develops during the course of this disease. Since the retinal nerve fiber layer (RNFL) is composed only of unmyelinated axons, measuring RNFL thickness represents a viable method of monitoring axonal loss in these patients. Optical coherence tomography (OCT) is a noninvasive, noncontact, accurate, and reproducible technique that quantitates the thickness of the peripapillary RNFL, fovea, and macula. Because of its potential role in defining axonal loss in ON and in assessing longitudinal changes in the RNFL before and after MS treatment, a multidisciplinary expert panel was charged with the following tasks: assess the current capabilities of OCT; review the current data about OCT, ON, and MS; and determine whether OCT could be a primary or secondary outcome measure in future MS clinical trials. The panel concluded that: [1] OCT is valid and reproducible; [2] OCT has yielded some important limited data concerning cross-sectional studies with ON and MS; [3] more studies are required to correlate OCT results with other measures of MS disease activity; [4] after correlation with these other measures and upon agreement of standardized technical and statistical methods, OCT may evolve into a important primary or secondary outcome metric for MS clinical trials and patient care. [Copyright &y& Elsevier]

Six pharmacological agents are currently approved for the treatment of multiple sclerosis (MS). However, all established substances are only partially effective in reducing disease progression or relapse rates. In addition, they have potentially serious side effects. Thus, significant efforts are being made to develop new agents or to optimize current therapies. The latter includes modifications of dose, route of administration or the time point of treatment initiation. In this review, we provide an update on the most important clinical phase II/III trials on approved and novel immunotherapeutic strategies in MS reported during the last two years. Pharmacotherapies include agents that target chemoattraction, cell migration, chemotherapies, and antigen-based therapies. [ABSTRACT FROM AUTHOR]

Introduction: Multiple Sclerosis represents a diagnostic and therapeutic challenge in developing countries since treatment delay is associated to disability while the costs of the approved pharmacological agents have a great economic impact. This Mexican consensus was developed with the aim to analyse the necessary procedures and requirements for the comprehensive care of the disease. Material and methods: A meeting consensus was carried out with the attendance of 21 physicians from seven states of the country, specialists in neurology, neuropediatrics, neuroepidemiology and neuroophthalmology, as well as professionals in areas of administration and teaching. The principal health institutions, both public and private, were represented. Results: The necessary diagnostic and therapeutic procedures were analysed according to scientific evidence; commentaries on availability in the country and guidelines and algorithms for their application were elaborated. Discussion: It is recommended that health institutions provide all the approved medications to allow physicians to choose the adequate treatment, according to the patient's condition. Authorization of ‘generic’ interferons (biosimilars) for sale or institutional use is a matter of concern for Mexican neurologists, since regulatory agencies with international impact (i.e. FDA, EMEA) have not approved these products because there is not evidence on their efficacy and safety, neither represent any economic advantage. The present guidelines constitute a medical proposal to develope Official Mexican Norms for the therapeutic management of multiple sclerosis. [ABSTRACT FROM AUTHOR]

• The risks and benefits of ocrelizumab use in older progressive MS patients are not known. • Age-related factors may contribute to disability, disease progression, and drug tolerability. • Older progressive MS patients on ocrelizumab trend towards decreased disability progression. • Ocrelizumab is generally safe and well tolerated in the older progressive MS subpopulation. Seminal trials evaluating anti-CD20 therapy in progressive MS primarily found benefit in younger, less-disabled patients with more inflammatory disease activity. The risks and benefits of ocrelizumab use in older patients with progressive froms of MS are not known. Retrospective chart review was performed for patients older than 55 with primary or secondary progressive MS at the time of ocrelizumab initiation. Clinical endpoints from 2 years prior to anti-CD20 therapy served as a within-subject control. Data was reviewed for 56 patients older than the age of 55 at the time of ocrelizumab initiation. Of 37 patients with 2-years of follow up on ocrelizumab, 40%(n=15) experienced confirmed disability progression (CDP) while 60% (n=22) remained stable or improved. 24 patients had data available for the within-subject control; for these patients, median age was 67, baseline EDSS 6.3, and disease duration 20.5 years. Prior to anti-CD20 therapy, 58% (n=14) of patients remained stable and 42% (n=10) experienced CDP. After ocrelizumab initiation, 71% (n=17) remained stable and 29% (n=7) experienced CDP. There was no difference between CDP (p=0.54) or change in EDSS (p=0.09) between time periods. Ocrelizumab was well tolerated and no difference in infection rate was seen using the within-subject control. We found no difference in clinical endpoints for patients on ocrelizumab compared to prior to anti-CD20 therapy; however, we could not exclude a modest effect given our sample size. Larger trials are needed to evaluate ocrelizumab use in this understudied MS subpopulation. [ABSTRACT FROM AUTHOR]

Background and purpose Natalizumab discontinuation induces the recurrence of multiple sclerosis disease activity: currently no therapeutic approach has been found able to abolish disease reactivation. Methods The recurrence of disease activity after natalizumab discontinuation was retrospectively evaluated in 79 patients who had been treated with immunomodulating agents, other first-line therapies, fingolimod or not treated. Results No differences have been found in clinical or magnetic resonance imaging recurrence of disease activity amongst the groups. Interestingly, no disease reactivation was observed only in one patient treated for 6 months with monthly pulses of cyclophosphamide. Conclusion Disease modifying treatment or 'no treatment' is unable to abolish disease activity reactivation after natalizumab discontinuation. [ABSTRACT FROM AUTHOR]

The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31 %) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups. [ABSTRACT FROM PUBLISHER]

Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a chronic systemic inflammatory disease that causes significant morbidity and mortality. The combined use of methotrexate and biological agents directed against tumor necrosis factor (TNF) has achieved significant improvement in clinical, radiographic and functional parameters not seen previously and has revolutionized the therapeutic goal of achieving remission in clinical, structural and functional parameters. The next goal should be to achieve remission without the use of biological drugs and later without medication. Although there is evidence about the efficacy and safety of TNF inhibitors, there is none on remission without the use of biological agents or disease modifying drugs. [ABSTRACT FROM AUTHOR]

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• Multiple sclerosis itself does not make pregnancy high risk. • Disease stability is recommended for at least one year prior attempting pregnancy. • Disease activity decreases during the third trimester and increases in postpartum. • Mode of delivery and use of epidural anesthesia are based on obstetrical criteria. • In women with MS, pregnancy should be considered when choosing treatment. Multiple sclerosis (MS) is the most common chronic immune-mediated neurological disorder in young adults, more frequently found in women than in men. Therefore, pregnancy-related issues have become an object of concern for MS professionals and patients. The aim of this work was to review the existing data to develop the first Argentine consensus for family planning and pregnancy in MS patients. A panel of expert neurologists from Argentina engaged in the diagnosis and care of MS patients met both virtually and in person during 2019 to carry out a consensus recommendation for family planning and pregnancy in MS. To achieve consensus, the procedure of the "formal consensus-RAND/UCLA method" was used. Recommendations were established based on published evidence and expert opinion focusing on pre-pregnancy counseling, pregnancy, and postpartum issues. The recommendations of these consensus guidelines are intended to optimize the management and treatment of MS patients during their reproductive age in Argentina. [ABSTRACT FROM AUTHOR]

Dysbiosis, associated with barrier disruption and altered gut-brain communications, has been associated with multiple sclerosis (MS). In this study, we evaluated the gut microbiota in relapsing-remitting patients (RRMS) receiving disease-modifying therapies (DMTs) and correlated these data with diet, cytokines levels, and zonulin concentrations. Stool samples were used for 16S sequencing and real-time PCR. Serum was used for cytokine determination by flow cytometry, and zonulin quantification by ELISA. Pearson's chi-square, Mann-Whitney, and Spearman's correlation were used for statistical analyses. We detected differences in dietary habits, as well as in the gut microbiota in RRMS patients, with predominance of Akkermansia muciniphila and Bacteroides vulgatus and decreased Bifidobacterium . Interleukin-6 concentrations were decreased in treated patients, and we detected an increased intestinal permeability in RRMS patients when compared with controls. We conclude that diet plays an important role in the composition of the gut microbiota, and intestinal dysbiosis, detected in RRMS patients could be involved in increased intestinal permeability and affect the clinical response to DTMs. The future goal is to predict therapeutic responses based on individual microbiome analyses (personalized medicine) and propose dietary interventions and the use of probiotics or other microbiota modulators as adjuvant therapy to enhance the therapeutic efficacy of DMTs.

Multiple sclerosis (MS) is usually diagnosed between twenty and forty years of age, when people often plan to have children. A lot has been said about the effect of pregnancy on the course of MS. The individual factors responsible for the disease modifying effect of pregnancy are not well determined. Having MS neither affects the fertility or the course of pregnancy itself. During pregnancy, many women find that their symptoms stay the same or even improve. Epidural and spinal analgesia appear to be safe and in general are not contraindicated for patients with MS. The management of disease-modifying treatments (DMTs) in pregnancy is a new issue for consideration in the clinical practice. There is limited information available into the safety of DMT use during pregnancy, especially for the most recent ones. In general, discontinuation of DMTs is recommended before conception to minimize risk of fetal harm. Women with very active MS before pregnancy who stop second-line treatments may show an increase in disease activity during pregnancy. Therefore, it might be discussed to maintain patients on DMTs until pregnancy is confirmed, and sometimes throughout pregnancy, to avoid a rebound of disease activity and severe relapses during pregnancy in very active patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: In patients with multiple sclerosis (MS), non-adherence to disease-modifying drug therapy is associated with an increased rate of MS relapses. Early identification of patients at risk of non-adherence would allow provision of timely and individualized support. The aim of the BETAPREDICT study was to investigate potential predictors of adherence in patients with MS in Germany treated with interferon β-1b (IFNβ-1b) using the BETACONNECT® autoinjector. Methods: BETAPREDICT was a national, multi-center, prospective, non-interventional, single-arm, 24-month cohort study of patients with relapsing-remitting MS or clinically isolated syndrome receiving IFNβ-1b via the BETACONNECT® autoinjector (ClinicalTrials.gov: NCT02486640). Injection data were captured by the autoinjector. The primary objective was to determine baseline predictors of compliance, persistence, and adherence to IFNβ-1b treatment after 12- and 24 months using multivariable-adjusted regression. Secondary objectives included evaluation of satisfaction with the autoinjector, injection site pain, vitamin and nutrient supplementation, clinical course, and patient-related outcome measures. Results: Of 165 patients enrolled, 153 were available for analysis (120 with autoinjector data). Seventy-two patients left the study prematurely. Compliance ( N = 120), persistence ( N = 153), and adherence ( N = 120) at 24 months were 89.1, 53.6, and 41.7%, respectively. Compliance at 12- and 24 months was predicted by intake of vitamin D supplements and absence of specific injection site reactions. Positive predictors of persistence included age (at 12- and 24 months) and previous duration of treatment (at 12 months), while intake of vitamins/nutrients other than vitamin D was a negative predictor (at 12 months). Positive predictors of adherence at 24 months were age and being experienced with IFNβ-1b. Higher scores in specific SF-36 subscales were positive predictors of medication-taking behavior at 24 months. Satisfaction with the autoinjector was high at baseline and 24 months (median score: 9 out of 10). Conclusions: Compliance with IFNβ-1b treatment among participants still under observation remained high over a 24-month period, while persistence and adherence continuously declined. Multiple factors affected medication-taking behavior, including patient characteristics, treatment history, injection site reactions, patients' perception of their health and support programs. The importance of these factors may differ among patients according to their individual situation., Competing Interests: WK received speaker honoraria and grant support from Bayer Vital, Grifols, Merck Serono, Novartis, Roche, and Teva. KB-G was an employee at Institut Dr. Schauerte during the analysis phase of the study. TZ received personal compensation from Almirall, Biogen, Bayer, Celgene, Novartis, Roche, Sanofi, and Teva for consulting and speaking services. TZ received additional financial support for research activities from Biogen, Novartis, Roche, Teva, and Sanofi. TN and MS are full-time employees of Bayer Vital GmbH. The authors declare that this study received funding from Bayer Vital GmbH. The funder was involved in the following way: conception, design, coordination and conduct of the study, analysis and interpretation of the data, drafting of the manuscript., (Copyright © 2021 Köhler, Bayer-Gersmann, Neußer, Schürks and Ziemssen.)

Very recent data from cohorts, such as that of the French Observatory of Multiple Sclerosis (OFSEP) and the MSBase cohort, are the subject of new statistical analyses using propensity scores that enable the matching of relapses frequency, EDSS, age, and sex ratio in patient populations for comparisons with each other, which reduces selection biases. The first data from these cohorts revealed a decline in transition to secondary progressive MS with the most effective disease-modifying drugs currently available, especially when these drugs were used early in the disease. However, these studies remain limited regarding the number of patients, the duration of follow-up, the use of imperfect methodologies, and the level of evidence remains low. The Gothenburg cohort in Sweden, which has been followed since the 1950s, found that 14% of benign non-progressive multiple sclerosis (MS) never evolved to secondary progression after more than 45 years of evolution. EDSS 7 was reached after 48 years of disease (median), and 50% evolved to secondary progressive MS after 15 years (consistent with data from the historic London, Ontario cohort). These data demonstrate that most people living with MS evolve without treatment to a significant long-term disability and that this evolution is closely linked to secondary progression (more than the relapse frequency). Benign forms appear as MS that never passes into secondary progressive MS. Recent data demonstrate that the delay until transition to secondary progression (more than 30 years in the MSBase cohort) and the delay in reaching EDSS 6 decreased since the introduction of disease-modifying drugs 20 years ago. However, randomized placebo-controlled trials do not last more than 2 or 3 years, and many biases may be involved in long-term follow-up studies: worsening patients who are lost to follow-up ("informative censoring" bias: only good responders to treatment remain primarily under the same long-term treatment and are followed); changes in the populations in the most recent studies with a lower rate of relapse and lower progression of disability at the beginning of the disease prior to initiating treatments; and environmental changes that remain largely misunderstood and may contribute to a natural evolution towards less severe disease., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Pregnancy influences the course of neuroimmunologic conditions, which include multiple sclerosis (MS), neuromyelitis optica spectrum disorder, and autoimmune encephalitis. The outcomes differ significantly for each disorder, reflecting the impact of hormonal changes, T-cell subsets, and placental factors on disease pathogenesis. In recent years, numerous data have emerged regarding MS activity throughout pregnancy and postpartum. Historically, the misconception that pregnancy worsens MS outcomes led patients to abstain from childbearing. Now, more women with these disorders, empowered by up-to-date information and better baseline disease control, are choosing to conceive. Nevertheless, the management of MS and related disorders in the pregnancy and postpartum period is complicated and requires a nuanced approach. Since standardized treatment guidelines around pregnancy are currently lacking, neurologists, together with obstetricians, must engage patients in a shared decision-making process that weighs the benefits to the mother and risks to the fetus. This chapter outlines the pathophysiology of neuroimmunologic disorders during pregnancy and postpartum, the impact of these diseases on childbearing, including fertility, pregnancy, delivery, and peurperium, as well as existing recommendations for treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)