Oxidative Modification of Blood Serum Proteins in Multiple Sclerosis after Interferon Beta and Melatonin Treatment

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Monika Adamczyk-Sowa

2017-01-01

Full Text Available Multiple sclerosis (MS is a disease involving oxidative stress (OS. This study was aimed at examination of the effect of melatonin supplementation on OS parameters, especially oxidative protein modifications of blood serum proteins, in MS patients. The study included 11 control subjects, 14 de novo diagnosed MS patients with the relapsing-remitting form of MS (RRMS, 36 patients with RRMS receiving interferon beta-1b (250 μg every other day, and 25 RRMS patients receiving interferon beta-1b plus melatonin (5 mg daily. The levels of N′-formylkynurenine, kynurenine, dityrosine, carbonyl groups, advanced glycation products (AGEs, advanced oxidation protein products (AOPP, and malondialdehyde were elevated in nontreated RRSM patients. N′-Formylkynurenine, kynurenine, AGEs, and carbonyl contents were decreased only in the group treated with interferon beta plus melatonin, while dityrosine and AOPP contents were decreased both in the group of patients treated with interferon beta and in the group treated with interferon beta-1b plus melatonin. These results demonstrate that melatonin ameliorates OS in MS patients supporting the view that combined administration of interferon beta-1b and melatonin can be more effective in reducing OS in MS patients than interferon beta-1b alone.

EХPERIENCE IN INTERFERON β-1A USE FOR TREATMENT OF MULTIPLE SCLEROSIS IN CHILDREN

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L. M. Kuzenkova

2013-01-01

Full Text Available Aim: to evaluate the impact of subcutaneous interferon β-1a on matrix metalloproteinases 3, 8, 9 (MMP, cytokines (tumor necrosis factor α — TNF α, and transforming growth factor β1 — TGF β1 levels in serum of children with relapsing-remitting multiple sclerosis. Patients and methods: the results of treatment of 32 patients with relapsing-remitting multiple sclerosis aged 12–18 years (22 girls and 10 boys were analyzed. Treatment efficacy was assessed by the number of relapsing-remitting multiple sclerosis exacerbations during 12 months, MRI data, MMP and cytokines dynamics in serum. Results: statistical evidence acquired for MMPs, their tissue inhibitor and cytokines levels decrease (p < 0,005 in patients receiving therapy with subcutaneous INF β-1a. Conclusions: subcutaneous interferon β-1а is highly efficient in treatment of relapsing-remitting multiple sclerosis in children and adolescents.

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

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Mahe J

2013-08-01

Full Text Available Julien Mahe,1 Aurélie Meurette,2 Anne Moreau,3 Caroline Vercel,2 Pascale Jolliet1,4 1Clinical Pharmacology Department, Institute of Biology, University Hospital, Nantes, France; 2Clinical Nephrology and Immunology Department, University Hospital, Nantes, France; 3Laboratory of Pathology, University Hospital, Nantes, France; 4EA 4275 Biostatistics, Pharmacoepidemiology and Subjective Measures in Health Sciences, University of Nantes, Nantes, France Abstract: Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. Keywords: thrombotic microangiopathy, interferon beta, hemolytic-uremic syndrome, antiangiogenic activity

Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis

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Polman, Chris H; Bertolotto, Antonio; Deisenhammer, Florian

2010-01-01

in MS and NAbs to interferon-beta therapy convened in Amsterdam, Netherlands, under the auspices of the Neutralizing Antibodies on Interferon beta in Multiple Sclerosis consortium, a European-based project of the 6th Framework Programme of the European Commission, to review and discuss data on NAbs......The identification of factors that can affect the efficacy of immunomodulatory drugs in relapsing-remitting multiple sclerosis (MS) is important. For the available interferon-beta products, neutralising antibodies (NAb) have been shown to affect treatment efficacy. In June, 2009, a panel of experts...... and their practical consequences for the treatment of patients with MS on interferon beta. The panel believed that information about NAbs and other markers of biological activity of interferons (ie, myxovirus resistance protein A [MxA]) can be integrated with clinical and imaging indicators to guide individual...

Efficacy of immunomodulatory therapy with interferon-β or glatiramer acetate on multiple sclerosis-associated uveitis.

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Velazquez-Villoria, D; Macia-Badia, C; Segura-García, A; Pastor Idoate, S; Arcos-Algaba, G; Velez-Escola, L; García-Arumí, J

2017-06-01

To analyse the role of interferon-β or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-β or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-β or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. Interferon β or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation

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Sellebjerg, F.; Krakauer, M.; Hesse, D.

2009-01-01

Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)-beta. NAbs impair the effect of treatment. The biological effect of IFN-beta can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other...

Treatment Satisfaction in Multiple Sclerosis

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Glanz, Bonnie I.; Musallam, Alexander; Rintell, David J.; Chitnis, Tanuja; Weiner, Howard L.; Healy, Brian C.

2014-01-01

Background: Disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) are associated with inconvenient methods of administration, significant side effects, and low adherence rates. This study was undertaken to compare treatment satisfaction in MS patients treated with interferon beta-1a intramuscular (IFNβ-1a IM), interferon beta-1a subcutaneous (IFNβ-1a SC), glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations between treatment satisfaction ra...

Early stage and long term treatment of multiple sclerosis with interferon-β

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Angela Applebee

2009-05-01

Full Text Available Angela Applebee, Hillel PanitchDepartment of Neurology, University of Vermont College of Medicine, and Neurology Service, Fletcher Allen Health Care, Burlington, VT, USAAbstract: Multiple sclerosis (MS affects young adults during the most productive years of their lives, and until recently many neurologists were limited to treating symptoms and attacks without any ability to alter the disease course. The 1990s ushered in an era of possibility with the approval of three interferon-beta (IFNβ therapies for the treatment of MS. Though the mechanism of action of these agents is not completely understood, it is clear they reduce magnetic resonance imaging (MRI activity as well as improve clinical outcomes. The principal randomized, blinded, multicenter trials of IFNβ all point to the need for early treatment soon after the diagnosis of MS is made. Efficacy has also been shown in patients treated after a first demyelinating event. Data on IFNβ in the treatment of secondary progressive MS (SPMS is not impressive, although it shows some benefit in SPMS patients who continue to experience MRI activity and clinical relapses, signifying a continued inflammatory component to their disease. There has been no proven efficacy of IFNβ in the treatment of primary progressive MS (PPMS. The IFNβ therapies are generally well tolerated with a favorable side effect profile. Despite benefits in MRI and clinical measures such as relapse rates and Expanded Disability Status Scale progression, patients continue to exhibit clinical progression and radiological atrophy, pointing to confounding factors and perhaps multiple etiologies of a disease that is not yet fully understood. In addition, the subject of neutralizing antibodies has recently assumed importance. The significance of these on treatment efficacy is uncertain, and until a universally accepted reliable assay is adopted, the decision to change treatment continues to rely on the clinical interpretation of

Interferon-beta in multiple sclerosis. Can we control its costs?

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Tolley, K H; Whynes, D K

1997-03-01

The recent licensing of interferon-beta for use in patients with multiple sclerosis has caused concern, in view of the equivocal evidence of efficacy, pressure of public expectation towards its use and the high expected cost if widespread use were to be sanctioned. Whether such alarm is justified remains a moot point. Owing to the limited range of circumstances of proven efficacy and the lack of cost-effectiveness data, it remains unclear whether sanctioned usage will proliferate to the anticipated extent. Unit costs may well fall in the future owing to competition in the pharmaceutical market. Interferon-beta is simply one example of a growing trend in actively promoted high-cost preparations over which rationing decisions will have to be reached.

Chromosomal radiosensitivity in patients with multiple sclerosis

International Nuclear Information System (INIS)

Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domínguez, Inmaculada

2013-01-01

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Chromosomal radiosensitivity in patients with multiple sclerosis

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Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: idomin@us.es [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)

2013-09-15

Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

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Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria

2003-01-01

Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

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Marta Sofia Mendes Oliveira

2015-09-01

Full Text Available Autoimmune hepatitis is a chronic liver inflammation resulting from deregulation of immune tolerance mechanisms. Multiple sclerosis is also an inflammatory disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Here we present a case of an 18 year old female with multiple sclerosis was treated with glatiramer acetate and with interferon beta 1a at our hospital. Seven months after initiating treatment, liver dysfunction occurred. Clinical and laboratory findings were suggestive of drug-induced hepatitis, which led to discontinuation of treatment with interferon. Facing a new episode of acute hepatitis one year later, she was subjected to a liver biopsy, and the analysis of autoantibodies was positive for smooth muscle antibodies. Given the diagnosis of autoimmune hepatitis she started therapy with prednisolone and azathioprine, with good clinical and analytical response. Besides, the demyelinating lesions of multiple sclerosis became lower. In conclusion, there are only a few cases that describe the association of autoimmune hepatitis with multiple sclerosis, and there is a chance both diseases have the same autoimmune inflammatory origin.

Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

DEFF Research Database (Denmark)

Kappos, Ludwig; Freedman, Mark S; Polman, Chris H

2009-01-01

with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon...... index (FAMS-TOI) at 5 years. Analysis of the primary endpoints was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00185211. FINDINGS: 235 (80%) patients from the early treatment and 123 (70%) from the delayed treatment group completed the 5-year study. Early treatment...

Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis

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Damiano Paolicelli

2009-07-01

Full Text Available Damiano Paolicelli, Vita Direnzo, Maria TrojanoDepartment of Neurological and Psychiatric Sciences, University of Bari, Bari, ItalyAbstract: Multiple sclerosis (MS is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. Since the 1990s the results of several clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions as assessed by magnetic resonance imaging. Long-term data suggest a persistent efficacy of IFNβ-1b on disease activity and a positive effect in slowing disability worsening. Furthermore a reduction of relapse rate and a slight positive effect on the progression were demonstrated when IFNβ-1b was administered to still-active secondary progressive MS. IFNβ-1b therapy is well tolerated and relatively free of long-term side effects. In spite of the emergence of new agents for the treatment of MS, IFNβ-1b still remains a first-line therapy with a fundamental role in all stages of the disease.Keywords: interferon beta-1b, relapsing-remitting multiple sclerosis, clinically isolated syndromes, efficacy, safety, neutralizing antibodies

Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial

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Sorensen, Per Soelberg; Lycke, Jan; Erälinna, Juha-Pekka

2011-01-01

Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy.......Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy....

Gene expression analysis of interferon-beta treatment in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, F.; Datta, P.; Larsen, J.

2008-01-01

by treatment with IFN-beta. We use DNA microarrays to study gene expression in 10 multiple sclerosis (MS) patients who began de novo treatment with IFN-beta. After the first injection of IFN-beta, the expression of 74 out of 3428 genes changed at least two-fold and statistically significantly (after Bonferroni......Treatment with interferon-beta (IFN-beta) induces the expression of hundreds of genes in blood mononuclear cells, and the expression of several genes has been proposed as a marker of the effect of treatment with IFN-beta. However, to date no molecules have been identified that are stably induced...

Occurrence of Psoriatic Arthritis during Interferon Beta 1a Treatment for Multiple Sclerosis

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Éric Toussirot

2014-01-01

Full Text Available Interferon beta (IFN-β is the first line therapy of relapsing-remitting multiple sclerosis. IFN-β is a cytokine that can contribute to the development of systemic autoimmune disease including psoriasis. The development or the exacerbation of psoriasis during IFN-β treatment has been previously observed. We report the occurrence of arthritis and dactylitis in a multiple sclerosis patient with preexisting psoriasis diagnosed as a psoriatic arthritis. The IL-23/Th17 pathway is involved in psoriasis and psoriatic arthritis and it has been suggested that IFN-β therapy in patients with Th17-mediated disease may be detrimental. Together with previous similar reports, our case suggests that IFN-β should certainly be used with caution in patients with concomitant systemic autoimmune disease with IL-23/Th17 involvement.

Reversible Pulmonary Arterial Hypertension Associated with Interferon-Beta Treatment for Multiple Sclerosis

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E Gibbons

2015-01-01

Full Text Available Interferon (IFN therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH, and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.

Gender effects on treatment response to interferon-beta in multiple sclerosis

DEFF Research Database (Denmark)

Magyari, M; Koch-Henriksen, N; Laursen, B

2014-01-01

BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

DEFF Research Database (Denmark)

Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

2016-01-01

OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment...... were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays...

Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.

Science.gov (United States)

Shirani, Afsaneh; Zhao, Yinshan; Karim, Mohammad Ehsanul; Evans, Charity; Kingwell, Elaine; van der Kop, Mia L; Oger, Joel; Gustafson, Paul; Petkau, John; Tremlett, Helen

2012-07-18

Interferon beta is widely prescribed to treat multiple sclerosis (MS); however, its relationship with disability progression has yet to be established. To investigate the association between interferon beta exposure and disability progression in patients with relapsing-remitting MS. Retrospective cohort study based on prospectively collected data (1985-2008) from British Columbia, Canada. Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (n = 959) cohorts. The main outcome measure was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 m; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability). A multivariable Cox regression model with interferon beta treatment included as a time-varying covariate was used to assess the hazard of disease progression associated with interferon beta treatment. Analyses also included propensity score adjustment to address confounding by indication. The median active follow-up times (first to last EDSS measurement) were as follows: for the interferon beta-treated cohort, 5.1 years (interquartile range [IQR], 3.0-7.0 years); for the contemporary control cohort, 4.0 years (IQR, 2.1-6.4 years); and for the historical control cohort, 10.8 years (IQR, 6.3-14.7 years). The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8%, 5.3%, and 23.1% in the 3 cohorts, respectively. After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort (hazard ratio, 1.30; 95% CI, 0.92-1.83; P = .14) or the historical control cohort (hazard ratio, 0

Cardiac arrhythmia with premature ventricular contractures induced by interferon beta in a patient with multiple sclerosis

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Igor Sobol

2015-03-01

Full Text Available Multiple sclerosis (MS is an immune-mediated inflammatory and neurodegenerative disease of the central nervous system. Interferon (IFN beta is an active ingredient of five out of twelve disease modifying treatments approved for MS. We report a case of IFN-beta-induced cardiac arrhythmia with premature ventricular contractures in a patient recently diagnosed with MS.

Immune activation in multiple sclerosis and interferon-beta therapy

DEFF Research Database (Denmark)

Krakauer, Martin

2007-01-01

The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

Clinical practice of analysis of anti-drug antibodies against interferon beta and natalizumab in multiple sclerosis patients in Europe

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Link, Jenny; Ramanujam, Ryan; Auer, Michael

2017-01-01

Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta...... positive test. Shorter times were observed for IFNβ-1b-Extavia s.c. (0.99 and 0.94 years) and natalizumab (0.25 and 0.23 years), which were introduced on the market when ADA testing was already available, as compared to IFNβ-1a i.m. (1.41 and 2.27 years), IFNβ-1b-Betaferon s.c. (2.51 and 1.96 years...

Higher Serum Uric Acid Levels in Multiple Sclerosis Patients After Longterm Interferon Beta Treatment

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Toncev Gordana

2017-10-01

Full Text Available Interferon beta is a safe and efficacious treatment for relapsing multiple sclerosis (MS. However, there is some evidence that uric acid, a scavenger of peroxynitrite, is involved in MS pathology and that increasing serum uric acid levels might have beneficial therapeutic effects. The aim of this study is to investigate serum uric acid levels in MS patients before and after long-term interferon beta treatment. Blood samples from 101 MS patients (53 receiving interferon beta 1a treatment and 48 receiving interferon beta 1b treatment; 28 male and 73 female; mean age at treatment onset 32,4±7,3 years; mean duration of disease at treatment onset 5,1±3,2 years; mean EDSS 2±1,3 before and after interferon beta treatment (mean treatment duration 3±2 years were analysed. Serum uric acid levels were measured using a quantitative enzymatic assay (Elitech Diagnostic, Sees, France. MS patients had significantly increased serum uric acid levels after treatment compared with those at the beginning of treatment (272,31±78,21 μmol/l vs. 210,17±53,65 μmol/l; p=0,019, Wilcoxon Mann-Whitney U-test. We did not find significant differences in serum uric acid levels between the interferon beta 1a and interferon beta 1b groups (p=0.98. These results indicate that one of the beneficial effects of interferon beta in MS might be based on the elevation of serum uric acid levels as a natural scavenger of peroxynitrite.

[Current therapy of multiple sclerosis].

Science.gov (United States)

Antonio García Merino, J

2014-12-01

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Multiple sclerosis

Science.gov (United States)

... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

[Biological treatment of multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, P.S.; Sellebjerg, F.

2008-01-01

In 1996 interferon (IFN)beta was the first biopharmaceutical product to be approved for the treatment of relapsing-remitting multiple sclerosis (MS). In 2006 the more potent monoclonal antibody natalizumab was approved. Presently, a number of monoclonal antibodies are being studied, including ale...

Diagnosis and treatment of latent tuberculosis in patients with multiple sclerosis, expert consensus. On behalf of the Colombian Association of Neurology, Committee of Multiple Sclerosis.

Science.gov (United States)

Navas, Carlos; Torres-Duque, Carlos A; Munoz-Ceron, Joe; Álvarez, Carlos; García, Juan R; Zarco, Luis; Vélez, Lázaro A; Awad, Carlos; Castro, Carlos Alberto

2018-01-01

Multiple sclerosis is an inflammatory and neurodegenerative demyelinating disease. Current treatment of multiple sclerosis focuses on the use of immunomodulatory, immunosuppressant, and selective immunosuppressant agents. Some of these medications may result in high risk of opportunistic infections including tuberculosis. The purpose of this study was to obtain consensus from a panel of neurologists, pulmonologists, infectious disease specialists, and epidemiology experts regarding the diagnosis, treatment, and monitoring of latent tuberculosis in patients with multiple sclerosis. A panel of experts in multiple sclerosis and tuberculosis was established. The methodological process was performed in three phases: definition of questions, answer using Delphi methodology, and the discussion of questions not agreed. Tuberculosis screening is suggested when multiple sclerosis drugs are prescribed. The recommended tests for latent tuberculosis are tuberculin and interferon gamma release test. When an anti-tuberculosis treatment is indicated, monitoring should be performed to determine liver enzyme values with consideration of age as well as comorbid conditions such as a history of alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver disease. Latent tuberculosis should be considered in patients with multiple sclerosis who are going to be treated with immunomodulatory and immunosuppressant medications. Transaminase level monitoring is required on a periodic basis depending on clinical and laboratory characteristics. In addition to the liver impairment, other side effects should be considered when Isoniazid is prescribed.

The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

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Mithu Storoni

2015-01-01

Full Text Available Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis

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Sørensen, P S; Sellebjerg, F; Lycke, J

2016-01-01

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. METHODS: This was a double......-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying...... were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence...

Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

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Iain Hargreaves

2018-02-01

Full Text Available Objectives: Evidence of mitochondrial respiratory chain (MRC dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS. However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05 in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3. Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3 was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s of action of β-interferon.

Patient subgroup analyses of the treatment effect of subcutaneous interferon beta-1a on development of multiple sclerosis in the randomized controlled REFLEX study

NARCIS (Netherlands)

Freedman, M.S.; De Stefano, N.; Barkhof, F.; Polman, C.H.; Comi, G.; Uitdehaag, B.M.J.; Casset-Semanaz, F.; Hennessy, B.; Lehr, L.; Stubinski, B.; Jack, D.L.; Kappos, L.

2014-01-01

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to

Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe

2012-01-01

the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells...

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

Science.gov (United States)

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

Systematic review of depression in patients with multiple sclerosis and its relationship to interferonβ treatment.

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Alba Palé, Leila; León Caballero, Jordi; Samsó Buxareu, Berta; Salgado Serrano, Purificación; Pérez Solà, Víctor

2017-10-01

Multiple sclerosis is a chronic disease considered the major cause of neurological disability in young adults worldwide. While depression is considered a determinant factor of impaired quality of life and poorer prognosis among patients with multiple sclerosis, it is very often dismissed and undertreated by physicians. Depression has been related to treatment with some immunomodulatory drugs, such as IFNβ. Data from patients who committed suicide during the pivotal study of interferon used as a disease modifying treatment in multiple sclerosis support this association. Moreover, there is plenty of evidence of neuropsychiatric toxicity caused by the use of IFNα as a treatment for other medical conditions. Although this link still remains relatively unknown, the presence of warnings regarding the possible relationship between depression and IFNβ led to restriction in medical indications in these patients. The purpose of this paper is to try to understand the reasons for an increased prevalence in depression in multiple sclerosis and to examine the impact that IFNβ treatment has on their mood. We performed a literature search on MEDLINE and Google Scholar databases applying PRISMA guidelines for systematic reviews. Studies were included if the participants were diagnosed with MS and prescribed IFNβ as the main treatment. We excluded non-english and full-text non available papers, as well as the articles where mental health was assessed exclusively as a feature of quality of life. The sample includes articles from 1980 to 2014, although filtration by year of publication was not applied and contains data from IFNβ-1a and IFNβ-1b. The Cochrane Collaboration Tool assessing risk of bias was used to determine the quality of the studies. Ten studies met full criteria for inclusion and final data extraction. The articles have heterogeneity regarding the samples, the methodology used and the expression of the results. Only three studies support the evidence of a

Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

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Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

2004-01-01

Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

Erupção acneiforme aguda induzida por interferon beta-1b durante tratamento para esclerose múltipla Acute acneiform eruption induced by interferon beta-1b during treatment for multiple sclerosis

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Dário Júnior de Freitas Rosa

2011-04-01

Full Text Available Esclerose múltipla é uma doença inflamatória desmielinizante, com presumida origem autoimune, que afeta o sistema nervoso central. A principal modalidade terapêutica é baseada no uso de imunomoduladores, como o interferon beta, que são geralmente bem tolerados. As manifestações cutâneas secundárias ao interferon beta-1b são representadas, na maioria das vezes, por reações no local de sua aplicação subcutânea. Descrevemos o caso de uma paciente do sexo feminino que desenvolveu um quadro de erupção acneiforme pelo interferon beta-1b.Multiple sclerosis is an inflammatory demyelinating disease of presumed autoimmune origin that affects the central nervous system. The main form of therapy is based on the use of immunomodulators such as interferon beta, which are usually well tolerated. Skin manifestations resulting from treatment with interferon beta-1b consist principally of reactions at the site of subcutaneous application of the drug. The present case report describes a female patient who developed an acneiform eruption resulting from treatment with interferon beta-1b.

CD26 + CD4 + T cell counts and attack risk in interferon-treated multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, F; Ross, C; Koch-Henriksen, Nils

2005-01-01

in patients with CD26 + CD4 + T cell counts above median, and this risk was independent of the risk conferred by neutralizing anti-IFN-beta antibodies. CD26 + CD4 + T cell counts may identify patients with MS at increased risk of attack during treatment with IFN-beta....... and CCR5 on T cells is altered in patients with active MS. We studied the expression of these molecules by flow cytometry in patients followed for six months during immunomodulatory treatment. In interferon (IFN)-beta-treated patients, we found that the hazard ratio for developing an attack was 28...

The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis

DEFF Research Database (Denmark)

Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

2008-01-01

Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein...... (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p...

Injectable interferon beta-1b for the treatment of relapsing forms of multiple sclerosis

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Slobodan M Jankovic

2010-03-01

Full Text Available Slobodan M JankovicPharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, SerbiaAbstract: Multiple sclerosis (MS is chronic inflammatory and demyelinating disease with either a progressive (10%–15% or relapsing-remitting (85%–90% course. The pathological hallmarks of MS are lesions of both white and grey matter in the central nervous system. The onset of the disease is usually around 30 years of age. The patients experience an acute focal neurologic dysfunction which is not characteristic, followed by partial or complete recovery. Acute episodes of neurologic dysfunction with diverse signs and symptoms will then recur throughout the life of a patient, with periods of partial or complete remission and clinical stability in between. Currently, there are several therapeutic options for MS with disease-modifying properties. Immunomodulatory therapy with interferon beta-1b (IFN-β1b or -1a, glatiramer and natalizumab shows similar efficacy; in a resistant or intolerant patient, the most recently approved therapeutic option is mitoxantrone. IFN-β1b in patients with MS binds to specific receptors on surface of immune cells, changing the expression of several genes and leading to a decrease in quantity of cell-associated adhesion molecules, inhibition of major histocompatibility complex class II expression and reduction in inflammatory cells migration into the central nervous system. After 2 years of treatment, IFN-β1b reduces the risk of development of clinically defined MS from 45% (with placebo to 28% (with IFN-β1b. It also reduces relapses for 34% (1.31 exacerbations annually with placebo and 0.9 with higher dose of IFN-β1b and makes 31% more patients relapse-free. In secondary-progressive disease annual rate of progression is 3% lower with IFN-β1b. In recommended doses IFN-β1b causes the following frequent adverse effects: injection site reactions (redness, discoloration, inflammation, pain, necrosis and non

Removal of valproic acid by plasmapheresis in a patient treated for multiple sclerosis

NARCIS (Netherlands)

Bastiaans, D.E.T.; Uden, I.W.M. van; Ruiterkamp, R.A.; Jong, B.A. de

2013-01-01

We present a case of a patient with multiple sclerosis who was treated with plasmapheresis and valproic acid. We used therapeutic drug monitoring to determine whether plasma concentrations of valproic acid were kept within the therapeutic window and to determine the amount of valproic acid that was

Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy

DEFF Research Database (Denmark)

Coles, Alasdair J; Twyman, Cary L; Arnold, Douglas L

2012-01-01

The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment....

NORdic trial of oral Methylprednisolone as add-on therapy to Interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial

DEFF Research Database (Denmark)

Sorensen, Per Soelberg; Mellgren, Svein Ivar; Svenningsson, Anders

2009-01-01

BACKGROUND: Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective, and new more effective and safe strategies are needed. Our aim was to assess the efficacy of oral methylprednisolone as an add-on therapy to subcutaneous interferon beta-1a to reduce...... was 0.22 for methylprednisolone compared with 0.59 for placebo (62% reduction, 95% CI 39-77%; pSleep disturbance and neurological and psychiatric symptoms were the most frequent adverse events recorded in the methylprednisolone group. Bone mineral density had not changed after 96 weeks......, these findings need to be corroborated in larger cohorts....

Treating fatigue in multiple sclerosis : Aerobic training

NARCIS (Netherlands)

Heine, M

2016-01-01

Multiple sclerosis (MS) is considered a chronic and debilitating autoimmune-mediated inflammatory and neurodegenerative disorder of the central nervous system. It is the number one neurological condition in young adults, affecting approximately 17.000 people in the Netherlands. Patients with MS

Improvement of fatigue in multiple sclerosis by physical exercise is associated to modulation of systemic interferon response.

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Mulero, Patricia; Almansa, Raquel; Neri, María José; Bermejo-Martin, Jesús Francisco; Archanco, Miguel; Arenillas, Juan Francisco; Téllez, Nieves

2015-03-15

Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the beneficial effect of exercise on this symptom are not clarified. Our aim was to evaluate gene expression profiles in MS patients who improved their fatigue status after an exercise program and to compare them with healthy controls (HC). Gene expression in whole blood was profiled at baseline in 7 HC and also in 7 fatigued-MS patients. Patients underwent an exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed. MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with HC that disappeared at the end of the program. Our results provide a biological basis for the observed benefit of exercise in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

[Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

Science.gov (United States)

Voltz, R; Goebels, N; Jarius, S; Hohlfeld, R

2002-05-06

The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

NARCIS (Netherlands)

Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

2014-01-01

Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

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Stanley Cohan MD, PhD

2015-03-01

Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

Pharmacogenomics of IFN-beta in multiple sclerosis: towards a personalized medicine approach

NARCIS (Netherlands)

Vosslamber, Saskia; van Baarsen, Lisa G. M.; Verweij, Cornelis L.

2009-01-01

Multiple sclerosis (MS) is an inflammatory disease of the CNS. The clinical presentation of MS is heterogeneous. Interferons (IFNs) were the first agents to show clinical efficacy in the treatment of MS and prolonged treatment is still the best available therapy. Although IFN treatment ameliorates

Critical review: assessment of interferon-β immunogenicity in multiple sclerosis

DEFF Research Database (Denmark)

Bendtzen, Klaus

2010-01-01

This review discusses type I interferon (IFN) immunogenicity with focus on methods of detection of anti-IFN antibodies in patients treated with human recombinant IFN-β. Pitfalls involved in the clinical use of various types of assays for binding antibodies and neutralizing antibodies against IFN-...... for individualized or personalized medicine, ie, optimizing therapies according to individual needs rather than using standardized trial-and-error regimens to all patients, is highlighted....

Critical review: assessment of interferon-ß immunogenicity in multiple sclerosis

DEFF Research Database (Denmark)

Bendtzen, Klaus

2010-01-01

This review discusses type I interferon (IFN) immunogenicity with focus on methods of detection of anti-IFN antibodies in patients treated with human recombinant IFN-ß. Pitfalls involved in the clinical use of various types of assays for binding antibodies and neutralizing antibodies against IFN-...... for individualized or personalized medicine, ie, optimizing therapies according to individual needs rather than using standardized trial-and-error regimens to all patients, is highlighted....

Multiple Sclerosis-related Uveitis: Does MS Treatment Affect Uveitis Course?

Science.gov (United States)

Jouve, Léa; Benrabah, Rabah; Héron, Emmanuel; Bodaghi, Bahram; Le Hoang, Phuc; Touitou, Valérie

2017-06-01

Few data are available regarding the optimal treatment of multiple sclerosis (MS)-related uveitis. The aim of this study was to describe clinical features of MS-associated uveitis and determine how MS treatment affects the course of uveitis. Retrospective, multicenter study. Patients were divided into two groups according to the use (group 2) or not (group 1) of immunomodulatory drugs. Characteristics of uveitis and treatment were reviewed. A total of 68 eyes from 36 patients (17 in group 1 and 19 in group 2) were included. All patients were treated with topical and/or systemic steroids for uveitis. Uveitis occurred 1-17 years prior to neurologic symptoms in 78% of patients. Uveitis was more severe in group 2 (puveitis (p = 0.06). MS-related uveitis has often a favorable evolution. Patients on interferon-beta have more severe and chronic uveitis. As far as we are concerned, interferon-beta given on the sole indication of uveitis is not recommended. If steroid-sparing agent is required for intraocular inflammation, immunosuppressive drugs should be considered.

Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

Science.gov (United States)

Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

2009-06-09

Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

Science.gov (United States)

English, Clayton; Aloi, Joseph J

2015-04-01

Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

Multiple Sclerosis: Immunopathology and Treatment Update

Science.gov (United States)

Dargahi, Narges; Katsara, Maria; Tselios, Theodore; Androutsou, Maria-Eleni; Matsoukas, John

2017-01-01

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. PMID:28686222

QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

Science.gov (United States)

Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

2016-04-01

Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p treatment in important QoL parameters beyond standard measures of relapse and disease severity.

Patient perceptions of multiple sclerosis and its treatment

Directory of Open Access Journals (Sweden)

de Seze J, Borgel F, Brudon F

2012-04-01

Full Text Available Jérôme de Seze1, Florent Borgel2, Frédérique Brudon31Department of Neurology CHRU de Strasbourg, Strasbourg, 2Medical Center, Grenoble, 3Clinique du Tonkin, Villeurbanne, FranceBackground: In order to improve the treatment outcome in multiple sclerosis, it is important to document the factors that influence adherence to therapy. The purpose of this study was to determine patient perceptions and awareness of multiple sclerosis and its treatment, treatment adherence, and impact on quality of life and daily living.Methods: This was a cross-sectional observational study performed in France. Each participating neurologist included the first three patients with relapsing-remitting multiple sclerosis who consulted after the start of the study. Data on clinical features were collected from a physician questionnaire and on disease and treatment perception and on quality of life from a patient autoquestionnaire.Results: A total of 175 neurologists entered 202 patients in the study. The mean duration of disease was 8.0 ± 7.0 years, and immunomodulatory treatment had been administered for a mean duration of 3.0 ± 2.0 years. A total of 166 patients (82.2% were treated with interferon-ß preparations and 36 patients (17.8% with glatiramer acetate. Eighty-five patients (42.1% reported missing their injections from time to time and 36 patients (17.8% reported “drug holidays”. The most frequently given reason for nonadherence was forgetfulness (38.7% of cases. Eighty-six patients (42.6% and 70 patients (34.7% claimed to be well informed about their disease and treatment, respectively. Adherence was significantly higher in well informed patients (P = 0.035. The majority of patients (176 patients, 87.1% intended continuing their current treatment and 49.5% considered that their current treatment might reduce relapses. The most frequently reported side effect was muscle pain (124 patients, 61.4%.Conclusion: Patient understanding of treatment for disease

INTERFERON BETA IN TREATMENT OF DISSEMINATED SCLEROSIS IN ADOLESCENTS — INFLUENCE ON NEUROPSYCHOLOGICAL STATUS AND PAROXYSMAL STATES

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A.N. Platonova

2010-01-01

Full Text Available Disseminated sclerosis is chronic progressive disease of central nervous system, which is characterized by demyelination, degeneration of nerve fibers and polymorphous clinical symptoms. According to literature data, 2–10% of patients have onset of a disease in childhood and adolescence. Frequent clinical symptoms of disseminated sclerosis, especially in adolescents, are paroxysmal states and neuropsychological disorders. Drugs containing interferon beta which are used for immunomodulating treatment, can increase the rate of paroxysmal neuropsychological disorders in patients with disseminated sclerosis. Present study with participation of 78 adolescents analyzed frequency and spectrum of neuropsychological disorders and paroxysmal states in patients 12–17 years old and relation of revealed disorders with a treatment with interferon beta.Key words: adolescents, disseminated sclerosis, interferon beta, treatment, depression, paroxysmal states, anxiety, neuropsychological testing.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:34-39

Interferon-alpha in the treatment of multiple myeloma

DEFF Research Database (Denmark)

Khoo, T.L.; Joshua, D.; Gibson, J.

2011-01-01

Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the hematological malignancy multiple myeloma. Interferon has been used......-induction agent with other chemotherapy regimens, and as maintenance therapy after conventional chemotherapy or complete remission after autologous or allogeneic transplantation. Interferon as a single induction agent or co-induction agent with other chemotherapy agents appears only to have minimal benefit...... in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

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Cefaro Luca

2009-10-01

Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

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Melendez-Torres, G J; Auguste, Peter; Armoiry, Xavier; Maheswaran, Hendramoorthy; Court, Rachel; Madan, Jason; Kan, Alan; Lin, Stephanie; Counsell, Carl; Patterson, Jacoby; Rodrigues, Jeremy; Ciccarelli, Olga; Fraser, Hannah; Clarke, Aileen

2017-09-01

At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. In total, 6420 publications were identified, of which 63 relating to 35 randomised

Cell-based therapeutic strategies for multiple sclerosis.

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Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis.

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Anne Waschbisch

Full Text Available The expression of selected microRNAs (miRNAs known to be involved in the regulation of immune responses was analyzed in 74 patients with relapsing remitting multiple sclerosis (RRMS and 32 healthy controls. Four miRNAs (miR-326, miR-155, miR-146a, miR-142-3p were aberrantly expressed in peripheral blood mononuclear cells from RRMS patients compared to controls. Although expression of these selected miRNAs did not differ between treatment-naïve (n = 36 and interferon-beta treated RRMS patients (n = 18, expression of miR-146a and miR-142-3p was significantly lower in glatiramer acetate (GA treated RRMS patients (n = 20 suggesting that GA, at least in part, restores the expression of deregulated miRNAs in MS.

SAFETY OF INTERFERON BETA 1A FOR A SUBCUTANEOUS ADMINISTRATION IN CHILDREN AND ADOLESCENTS WITH DISSEMINATED SCLEROSIS

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O.V. Bykova

2008-01-01

Full Text Available The onset of disseminated sclerosis occurs in childhood and juvenile age in 10% of patients. nevertheless, all immunomodulatory drugs for a treatment of this disease intended for adult population of patients, and there's an age limitation to the administration of these medications. There's only one interferon beta in group of «changing the clinical course of disseminated sclerosis medications», that was annotated to the administration in patients from 16 years. It's interferon betab1a (Rebif for subcutaneous administration in 22 ?g and 44 ?g dosage. This drug was well known as an effective and safe medication for a long term administration for a long time in adult neurological practice. But doctors have to use interferon betab1a «off label» yet in patients younger 16 years in Russia and in other countries, comparing risk of changing the regimen of age limitation and risk of deprivation of un derbaged patient of years of qualitative life.Key words: children, disseminated sclerosis, interferon beta 1a, treatment.

Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.

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Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana

Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Adherence to interferon β-1b treatment in patients with multiple sclerosis in Spain.

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Oscar Fernández

Full Text Available Adherence to interferon β-1b (INFβ-1b therapy is essential to maximize the beneficial effects of treatment in multiple sclerosis (MS. For that reason, the main objectives of this study are to assess adherence to INFβ-1b in patients suffering from MS in Spain, and to identify the factors responsible for adherence in routine clinical practice.This was an observational, retrospective, cross-sectional study including 120 Spanish patients with MS under INFβ-1b treatment. Therapeutic adherence was assessed with Morisky-Green test and with the percentage of doses received. The proportion of adherent patients assessed by Morisky-Green test was 68.3%, being indicative of poor adherence. Nevertheless, the percentage of doses received, which was based on the number of injected medication, was 94.3%. The main reason for missing INFβ-1b injections was forgetting some of the administrations (64%. Therefore, interventions that diminish forgetfulness might have a positive effect in the proportion of adherent patients and in the percentage of doses received. In addition, age and comorbidities had a significant effect in the number of doses injected per month, and should be considered in the management of adherence in MS patients.Among all the available methods for assessing adherence, the overall consumption of the intended dose has to be considered when addressing adherence.

Factors affecting bone mineral density in multiple sclerosis patients

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Ayatollahi, Azin; Mohajeri-Tehrani, Mohammad Reza

2013-01-01

Background Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD). Methods 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years) participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA). The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS). The patient's quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29). Results Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI) of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs) pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001), but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL), disease duration and BMD of both site. Conclusion As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients’ treatment protocols

Natalizumab for the treatment of relapsing multiple sclerosis

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Richard A Rudick

2008-06-01

Full Text Available Richard A Rudick1, Michael A Panzara21Cleveland Clinic Foundation, Cleveland, OH, USA; 2Biogen Idec, Inc., Cambridge, MA, USAAbstract: Natalizumab is an α4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS, based on demonstrated efficacy in the pivotal AFFIRM study (N = 942. Natalizumab monotherapy reduced risk of disability progression by 42%–54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was also associated with significant reductions in number of T2-hyperintense, gadolinium-enhancing, and T1-hypointense lesions and in volume of T2-hyperintense lesions (all p < 0.001 on magnetic resonance imaging. Furthermore, natalizumab-treated patients in AFFIRM experienced significant improvements from baseline in the physical and mental components of the Short Form-36 (p ≤ 0.01 and a 35% reduction in risk of clinically significant vision loss (p = 0.008 vs placebo. Natalizumab was well tolerated in phase 3 studies. Common adverse events were generally mild and included headache, fatigue, urinary tract infections, and arthralgia. Serious adverse events were similar between treatment groups. The incidence of serious hypersensitivity reactions associated with natalizumab was <1%. Progressive multifocal leukoencephalopathy was a rare complication of treatment, observed in 2 patients with MS who received natalizumab plus interferon β-1a. The robust clinical benefits of natalizumab, including benefits on patient-reported quality of life, make it an important addition to disease-modifying therapies available to patients with relapsing MS.Keywords: multiple sclerosis, natalizumab, α4-integrin antagonist

Multiple sclerosis

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Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

2008-01-01

Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

Understanding and meeting injection device needs in multiple sclerosis: a survey of patient attitudes and practices

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Russell S

2011-03-01

Full Text Available Elisabetta Verdun di Cantogno1, Susan Russell2, Tom Snow21Global Clinical Development Unit, Merck Serono S.A. – Geneva, Switzerland; 2Global Marketing, Merck Serono S.A. – Geneva, SwitzerlandBackground: All established disease-modifying drugs for multiple sclerosis require parenteral administration, which can cause difficulties for some patients, sometimes leading to suboptimal adherence. A new electronic autoinjection device has been designed to address these issues.Methods: Patients with relapsing multiple sclerosis currently receiving subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, or glatiramer acetate completed an online questionnaire (July 4–25, 2008 that surveyed current injection practices, experiences with current injection methods, and impressions and appeal of the new device.Results: In total, 422 patients completed the survey, of whom 44% used autoinjectors, 43% prefilled syringes, and 13% syringes and vials; overall, 66% currently self-injected. Physical and psychological barriers to self-injection included difficulty with injections, needle phobia, and concerns over correct injection technique. Only 40% of respondents were “very satisfied” with their current injection method. The new electronic autoinjector was rated as “very appealing” by 65% of patients. The benefits of the new device included the ability to customize injection settings and to review dosing history.Conclusion: New technologies may help patients overcome physical and psychological barriers to self-injection. The combination of a reliable and flexible autoinjection device with dose-monitoring technology may improve communication between health care professionals and patients, and improve treatment adherence.Keywords: adherence, autoinjection, subcutaneous interferon beta-1a, multiple sclerosis 

Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis

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Bachelet, Delphine; Hässler, Signe; Mbogning, Cyprien

2016-01-01

Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in S...

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

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Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

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Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of glatiramer acetate in the early treatment of multiple sclerosis

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David W Brandes

2010-06-01

Full Text Available David W BrandesHope MS Center, Knoxville, TN, USA; ULCA, Los Angeles, CA, USAAbstract: The treatment of the underlying disease process causing multiple sclerosis has continued to evolve since the initial approval of interferon-beta-1b in 1993. Current emphasis is on early treatment, including treatment after a single clinical attack (clinically isolated syndrome. The assessment of which disease modifying medication to use as initial therapy has continued to remain a combination of science and the art of medicine. Equally important are the assessment of treatment failure and the subsequent choice of medication change. This article will present scientific information, as well as information about clinical decision making, about these choices, with emphasis on the changing role of glatiramer acetate in this process.Keywords: glatiramer acetate, early treatment, multiple sclerosis

Interferon-beta for relapsing-remitting multiple sclerosis: a systematic review

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Dian HE

2014-09-01

Full Text Available Objective To assess the efficacy and safety of interferon-beta (IFN-β as monotherapy versus placebo for patients with relapsing-remitting multiple sclerosis (RRMS.  Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL, PubMed, EMBASE, CINAHL, LILACS, PEDRO, China Biology Medicine Disc (CBMDisc, as well as clinical trial registries and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP, retrieval deadline: June 2014. Furthermore, we checked reference lists of published reviews and retrieved articles, and communicated personally with investigators and biotechnology companies participating in trials of IFN-β in an effort to identify further studies or unpublished data. Two review authors independently screened studies, extracted data and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Manager software (Version 5.3.3 and the impacts of limitations in study design or execution (risk of bias, inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the quality of the body of evidence were assessed.  Results A total of 576 articles were retrieved. After screening of titles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for further assessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS (high-dose IFN-β group: N = 1076; placebo group: N = 1053. All studies were randomized, double-blind, controlled, parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo as monotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk of attrition bias. Moreover, the intention to treat (ITT principle was not used in data analysis. Data from only 919 patients (43.17% were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated

Subcutaneous interferon β-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study.

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Krupp, Lauren B; Pohl, Daniela; Ghezzi, Angelo; Boyko, Alexey; Tenembaum, Silvia; Chen, Liang; Aycardi, Ernesto; Banwell, Brenda

2016-04-15

To further understand management of pediatric patients with multiple sclerosis (MS), we examined disease features, clinical practice patterns, and response to treatment in the United States (US) and seven other countries ('rest of World'; ROW). Anonymized data, recorded as part of routine clinical practice, were obtained from medical records (1997-2009) of study participants (who received subcutaneous interferon β-1a before age 18 years) from the US and ROW. Samples were stratified by age (preadolescents [managed differently, compared with ROW patients. Future prospective studies are needed to confirm these observations and ascertain their clinical significance. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

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Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

2011-01-01

On the basis of various clinical and MRI measurements, the phase 3 Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) study in patients with relapsing-remitting multiple sclerosis (RRMS) showed that short-course oral treatment with cladribine at cumulative doses of 3·5 and 5·25 mg...

The Danish Multiple Sclerosis Treatment Register

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Magyari M

2016-10-01

Full Text Available Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion: The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. Keywords: multiple sclerosis, epidemiology, immunomodulatory treatment, neutralizing antibodies, observational studies, registry research, disease modifying therapy

A "candidate-interactome" aggregate analysis of genome-wide association data in multiple sclerosis

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Mechelli, Rosella; Umeton, Renato; Policano, Claudia

2013-01-01

of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge......, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate...... immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated...

Neuromyelitis optica-like pathology is dependent on type I interferon response

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Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin

2013-01-01

Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in ...

Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study.

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Sørensen, P S; Sellebjerg, F; Lycke, J; Färkkilä, M; Créange, A; Lund, C G; Schluep, M; Frederiksen, J L; Stenager, E; Pfleger, C; Garde, E; Kinnunen, E; Marhardt, K

2016-05-01

Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy. This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy. © 2016 EAN.

Therapeutic use of sport climbing for patients with multiple sclerosis

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Ana Ožura

2009-05-01

Full Text Available Sport climbing is a form of exercise that requires complex and variable movement. Because of the use of the so-called "top-rope system", this is a safe activity appropriate for individuals with physical disabilities. Therefore, climbing might prove to be an effective form of therapy for patients with multiple sclerosis. Multiple sclerosis is a chronic neurological disease that may include motor and cognitive deficits as well as affective disturbances. The illness is characterized by multifocal areas of brain damage (plaques, as consequence of autoimmune inflammation. Sport climbing might be a potentially useful activity for treating spasticity, improving a person's self image and certain aspects of cognition, such as attention and executive functions, as well as for managing emotional disturbances. All of the above are areas where patients with multiple sclerosis might be in need of assistance. The article also describes the experience of a patient with multiple sclerosis who was enrolled in our climbing program. Future research is needed to evaluate the effect of climbing therapy for patients with multiple sclerosis.

Vascular comorbidities in multiple sclerosis

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Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

2016-01-01

To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

Rehabilitation and multiple sclerosis

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Dalgas, Ulrik

2011-01-01

In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis.

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Ramos González, E J; Ramirez Jirano, L J; García Martínez, D Z; Ortiz, G G; Jave Suárez, L F; Leal Cortes, C A; Bitzer Quintero, O K

2018-03-08

Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA). EAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-β, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded. All immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-β and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1β and IL-12p70 concentrations. However, IFN-β and MLT did decrease CSF TNF-α concentrations. Further studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab

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Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

2016-01-01

Background Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity.  Objective To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in ...

HOW DOES FINGOLIMOD (GILENYA® FIT IN THE TREATMENT ALGORITHM FOR HIGHLY ACTIVE RELAPSING-REMITTING MULTIPLE SCLEROSIS?

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Franz eFazekas

2013-05-01

Full Text Available Multiple sclerosis (MS is a neurological disorder characterised by inflammatory demyelination and neurodegeneration in the central nervous system (CNS. Until recently, disease modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya® is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS for adult patients with high disease activity despite basic treatment (beta-interferon and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from 10 Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

Orthognathic Surgery in a Patient with Multiple Sclerosis.

Science.gov (United States)

Al-Bazie, Saleh A

2015-06-01

The aim of this paper was to report a case of orthognathic surgery successfully done in a patient with multiple sclerosis. Multiple sclerosis (MS) is a chronic, progressive inflammatory disorder of the central nervous system affecting young adults, characterized by lymphocytic infiltration of the brain and spinal cord leading to demyelination and focal axonal damage. Clinically, MS patients present with reversible neurological dysfunction in the early stages, which progresses to irreversible neurological disability and deficit. Oral manifestations of MS include facial numbness or pain, neuralgias, facial paralysis, dysarthria and dysphagia. While dental treatment is not contraindicated in MS patients, it is, however, limited to preventive and supportive dental care. A 23-year-old Saudi male patient with a diagnosis of MS since 2008 reported to the oral and maxillo-facial surgery (OMFS) department for correction of dentofacial deformity. The patient was under follow-up with the neurology department and was being treated with interferon beta-1a. Following consent from the neurologist and the patient, a Lefort 1 segmental osteotomy was done under general anesthesia. The patient was stable throughout the surgical procedure and during the postoperative period. The patient was discharged upon complete surgical recovery and no acute exacerbations of MS were reported during the perioperative period. Based on our observations, orthognathic and maxillofacial surgical procedures can be safely carried out in patients with MS, provided a strict perioperative prophylactic regimen for stress reduction and prevention of acute attacks of MS is adhered to. Due to the stressful nature of dental treatment and oral and maxillofacial surgical procedures, acute exacerbations of MS are very much likely. Hence, it is imperative that dental and oral surgical practitioners are aware of the manifestations of MS and are able to manage such patients with suitable treatment modifications.

Fatigue and Multiple Sclerosis

Science.gov (United States)

... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

Variants of Interferon Regulatory Factor 5 are Associated with Neither Neuromyelitis Optica Nor Multiple Sclerosis in the Southeastern Han Chinese Population

Institute of Scientific and Technical Information of China (English)

Qi-Bing Liu; Lei Wu; Gui-Xian Zhao; Ping-Ping Cai; Zhen-Xin Li; Zhi-Ying Wu

2015-01-01

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are demyelinating disorders of the central nervous system.Interferon regulatory factor 5 (IRF5) is a common susceptibility gene to different autoimmune disorders.However,the association of IRF5 variants with NMO and MS patients has not been well studied.Therefore,we aimed to evaluate whether IRF5 variants were associated with NMO and MS in the Southeastern Han Chinese population.Methods:Four single nucleotide polymorphisms (SNPs) were selected and genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry in 111 NMO patients,145 MS patients and 300 controls from Southeastern China.Results:None of these 4 SNPs was associated with NMO or MS patients.Conclusions:Our preliminary study indicates that genetic variants in IRF5 may affect neither NMO nor MS in the Southeastern Han Chinese population.Further studies with a large sample size and diverse ancestry populations are needed to clarify this issue.

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, Egon; Stenager, E N; Knudsen, Lone

1994-01-01

In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

Increased rate of treatment with antidepressants in patients with multiple sclerosis

DEFF Research Database (Denmark)

Kessing, Lars Vedel; Harhoff, Mette; Andersen, Per Kragh

2008-01-01

The prevalence of depression and anxiety is increased in patients with multiple sclerosis, but it has not been investigated whether these conditions are treated in clinical practice. The objective of this study was to investigate whether the rate of treatment with antidepressants is increased...... in patients with multiple sclerosis compared with patients with other chronic illnesses and compared with the general population. By linkage of nationwide case registers, all patients were identified, who had received a main diagnosis of multiple sclerosis or osteoarthritis at first admission or during...... outpatient contact in the period 1995-2000 in Denmark. Rates of subsequent purchase of antidepressants for these patients were calculated. In total, 417 patients with a main diagnosis of multiple sclerosis and 12 127 patients with a main diagnosis of osteoarthritis, at first discharge from hospital...

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

Science.gov (United States)

Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael

2018-02-13

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Hematopoietic stem cell transplantation in multiple sclerosis

DEFF Research Database (Denmark)

Rogojan, C; Frederiksen, J L

2009-01-01

Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

Interferon alpha association with neuromyelitis optica

DEFF Research Database (Denmark)

Asgari, Nasrin; Voss, Anne; Steenstrup, Troels

2013-01-01

Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population...

Multiple sclerosis and organic solvents

DEFF Research Database (Denmark)

Mortensen, J T; Brønnum-Hansen, Henrik; Rasmussen, K

1998-01-01

We investigated a possible causal relation between exposure to organic solvents in Danish workers (housepainters, typographers/printers, carpenters/cabinetmakers) and onset of multiple sclerosis. Data on men included in the Danish Multiple Sclerosis Register (3,241 men) were linked with data from......, and butchers. Over a follow-up period of 20 years, we observed no increase in the incidence of multiple sclerosis among men presumed to be exposed to organic solvents. It was not possible to obtain data on potential confounders, and the study design has some potential for selection bias. Nevertheless......, the study does not support existing hypotheses regarding an association between occupational exposure to organic solvents and multiple sclerosis....

Does vagotomy protect against multiple sclerosis?

Science.gov (United States)

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

The Danish multiple sclerosis treatment register

DEFF Research Database (Denmark)

Magyari, Melinda; Koch-Henriksen, Nils; Sørensen, Per Soelberg

2016-01-01

Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR) serves as a clinical quality register, enabling the health authorities to monitor the quality of the diseasemodifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR...... includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main...... variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start...

Multiple sclerosis: Pregnancy and women's health issues.

Science.gov (United States)

Mendibe Bilbao, M; Boyero Durán, S; Bárcena Llona, J; Rodriguez-Antigüedad, A

2016-08-18

The course of multiple sclerosis (MS) is influenced by sex, pregnancy and hormonal factors. To analyse the influence of the above factors in order to clarify the aetiopathogenic mechanisms involved in the disease. We conducted a comprehensive review of scientific publications in the PubMed database using a keyword search for 'multiple sclerosis', 'MS', 'EAE', 'pregnancy', 'hormonal factors', 'treatment', and related terms. We reviewed the advances presented at the meeting held by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in March 2013 in London, as well as recommendations by international experts. We provide recommendations for counselling and treating women with MS prior to and during pregnancy and after delivery. Current findings on the effects of treatment on the mother, fetus, and newborn are also presented. We issue recommendations for future research in order to address knowledge gaps and clarify any inconsistencies in currently available data. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of neuromuscular electrostimulation in the treatment of dysphagia in patients with multiple sclerosis

NARCIS (Netherlands)

Bogaardt, Hans; van Dam, Danielle; Wever, Nienke M.; Bruggeman, Caroline E.; Koops, Johan; Fokkens, Wytske J.

2009-01-01

OBJECTIVES: We explored the possible effects of neuromuscular electrostimulation on the swallowing function of patients with multiple sclerosis and swallowing problems. METHODS: Twenty-five patients (average age, 53.1 years; SD, 9.8 years) with multiple sclerosis and swallowing problems were treated

Extracorporeal shock wave therapy for injection site panniculitis in multiple sclerosis patients.

Science.gov (United States)

Stieger, Marco; Schmid, Jean-Paul; Yawalkar, Nikhil; Hunziker, Thomas

2015-01-01

Painful cutaneous injection site reactions may hamper treatment with interferon β (IFN-β) and glatiramer acetate (GA) in multiple sclerosis (MS) patients. To maintain therapy adherence, efficient therapeutic modalities for these subcutaneous inflammatory lesions are urgently needed. We tested the application of local extracorporeal shock wave therapy (ESWT). We applied 5 sessions of ESWT to 8 patients suffering from MS who had developed painful panniculitis at the injection sites of either IFN-β or GA. Clinical outcomes, i.e. pain reduction and regression of induration, were assessed 3 and 6 months after completion of the ESWT using a visual analogue score. All patients showed both significant pain reduction and reduction of the skin induration in the treated lesions, while in untreated control lesions there was no improvement. ESWT proved to be a non-invasive, safe and efficient physical treatment modality for injection-induced painful cutaneous side effects of disease-modifying drugs in MS. © 2014 S. Karger AG, Basel.

Multiple sclerosis

International Nuclear Information System (INIS)

Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

1986-01-01

Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

DEFF Research Database (Denmark)

Møller, M; Søndergaard, Helle B; Koch-Henriksen, N

2014-01-01

OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We...... impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031). CONCLUSIONS: CCR5 Δ32 is not associated with lower disease...

Treatment of Cognitive Impairment in Multiple Sclerosis

Science.gov (United States)

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Clinical Manifestations of Multiple Sclerosis in Taiwanese Children

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2006-11-01

Full Text Available Twenty-one patients with multiple sclerosis (MS and onset before 18 years were treated over the past 22 years and their records retrospectively analyzed at the National Taiwan University Hospital, Taipei, and Min-Sheng General Hospital, Taoyuan, Taiwan.

Multiple Sclerosis After Infectious Mononucleosis

DEFF Research Database (Denmark)

Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

2007-01-01

BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish...... Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...

Treatment of Cognitive Impairment in Multiple Sclerosis

OpenAIRE

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the co...

Teriflunomide for multiple sclerosis in real-world setting

DEFF Research Database (Denmark)

Elkjær, Maria Louise; Molnar, T; Illes, Z

2017-01-01

OBJECTIVES: Teriflunomide 14 mg is a once-daily oral disease-modifying treatment for relapsing-remitting multiple sclerosis. We examined adverse event (AE) profile and efficacy in real life. MATERIALS AND METHODS: In this observational cohort study, we retrospectively examined 1521 blood samples...... and data of 102 patients followed for up to 28 months. RESULTS: The number of female patients starting teriflunomide peaked in the fifth decade, 10 years later compared to male patients (Ptreatment...... with interferon-beta. Expanded disability status scale improved in 11% of patients (18.2±3.6 months follow-up) and remained constant in 67.5% (15±5.3 months follow-up). Of ten relapses, three occurred within 6 months after starting treatment. Seventeen patients (16.5%) discontinued teriflunomide: 53% because...

Multiple Sclerosis and Vitamin D

Science.gov (United States)

... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT ... caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided ...

ExtaviJect® 30G device for subcutaneous self-injection of interferon beta-1b for multiple sclerosis: a prospective European study

Directory of Open Access Journals (Sweden)

Boeru G

2013-11-01

Full Text Available Gabriel Boeru,1 Ivan Milanov,2 Francesca De Robertis,3 Wojciech Kozubski,4 Michael Lang,5 Sònia Rojas-Farreras,6 Mark Tomlinson7 1Military Hospital, Bucharest, Romania; 2University Hospital Saint Naum, Sofia, Bulgaria; 3Department of Neurology, Vito Fazzi Hospital of Lecce, Lecce, Italy; 4Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland; 5NeuroPoint Patient Academy and Neurological Practice, Ulm, Germany; 6IMS Health, Barcelona, Spain; 7Novartis Pharma AG, Basel, Switzerland Background: The ExtaviJect® 30G autoinjector was developed to facilitate parenteral self-administration of interferon beta-1b (Extavia®, a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9 and EuroQol-5 Dimension (EQ-5D instruments, respectively. Results: Of 582 patients enrolled, 568 (98% received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93% attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97% patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%–98% of patients and 59%–98% of nurses were in agreement. There were nine serious adverse events (four disease-related reported among the 227 (39

[Future challenges in multiple sclerosis].

Science.gov (United States)

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Managing the oral side-effects of medications used to treat multiple sclerosis.

Science.gov (United States)

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

Therapeutic compliance of first line disease-modifying therapies in patients with multiple sclerosis. COMPLIANCE Study.

Science.gov (United States)

Saiz, A; Mora, S; Blanco, J

2015-05-01

Non-adherence to disease-modifying therapies (DMTs) in multiple sclerosis may be associated with reduced efficacy. We assessed compliance, the reasons for non-compliance, treatment satisfaction, and quality of life (QoL) of patients treated with first-line therapies. A cross-sectional, multicenter study was conducted that included relapsing multiple sclerosis patients. Compliance in the past month was assessed using Morisky-Green test. Seasonal compliance and reasons for non-compliance were assessed by an ad-hoc questionnaire. Treatment satisfaction and QoL were evaluated by means of TSQM and PRIMUS questionnaires. A total of 220 patients were evaluated (91% relapsing-remitting); the mean age was 39.1 years, 70% were female, and the average time under treatment was 5.4 years. Subcutaneous interferon (IFN) β-1b was used in 23% of the patients, intramuscular IFN β-1a in 21%, subcutaneous IFN β-1a in 37%, and with glatiramer acetate in 19%. The overall compliance was 75%, with no significant differences related to the therapy, and 81% did not report any seasonal variation. Compliant patients had significantly lower disability scores and time of diagnosis, and greater satisfaction with treatment and its effectiveness. Discomfort and flu-like symptoms were the most frequent reasons for non-compliance. The satisfaction and QoL were associated with less disability and number of therapeutic switches. The rate of compliance, satisfaction and QoL in multiple sclerosis patients under DMTs is high, especially for those newly diagnosed, less disabled, and with fewer therapeutic switches. Discomfort and flu-like symptoms associated with injected therapies significantly affect adherence. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

Science.gov (United States)

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

MicroRNA Expression Changes during Interferon-Beta Treatment in the Peripheral Blood of Multiple Sclerosis Patients

Directory of Open Access Journals (Sweden)

Georg Füllen

2013-08-01

Full Text Available MicroRNAs (miRNAs are small non-coding RNA molecules acting as post-transcriptional regulators of gene expression. They are involved in many biological processes, and their dysregulation is implicated in various diseases, including multiple sclerosis (MS. Interferon-beta (IFN-beta is widely used as a first-line immunomodulatory treatment of MS patients. Here, we present the first longitudinal study on the miRNA expression changes in response to IFN-beta therapy. Peripheral blood mononuclear cells (PBMC were obtained before treatment initiation as well as after two days, four days, and one month, from patients with clinically isolated syndrome (CIS and patients with relapsing-remitting MS (RRMS. We measured the expression of 651 mature miRNAs and about 19,000 mRNAs in parallel using real-time PCR arrays and Affymetrix microarrays. We observed that the up-regulation of IFN-beta-responsive genes is accompanied by a down-regulation of several miRNAs, including members of the mir-29 family. These differentially expressed miRNAs were found to be associated with apoptotic processes and IFN feedback loops. A network of miRNA-mRNA target interactions was constructed by integrating the information from different databases. Our results suggest that miRNA-mediated regulation plays an important role in the mechanisms of action of IFN-beta, not only in the treatment of MS but also in normal immune responses. miRNA expression levels in the blood may serve as a biomarker of the biological effects of IFN-beta therapy that may predict individual disease activity and progression.

Advances in the treatment of relapsing–remitting multiple sclerosis – critical appraisal of fingolimod

Directory of Open Access Journals (Sweden)

Gasperini C

2013-03-01

Full Text Available Claudio Gasperini,1 Serena Ruggieri,2 Chiara Rosa Mancinelli,2 Carlo Pozzilli2 1Department of Neurosciences, S Camillo Forlanini Hospital, Rome, Italy; 2Department of Neurology and Psychiatry, Sapienza – University of Rome, Rome, Italy Abstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs for MS in Europe, and two second-line treatments. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side effects. Despite disease-modifying drugs being well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Therefore, the development of new therapeutic strategies is warranted. Several oral compounds are in late stages of development for treating MS. Fingolimod is an oral sphingosine-1-phosphate receptor modulator that has demonstrated superior efficacy compared with placebo and interferon β-1a in phase III studies. It has already been approved in the treatment of MS. This review focuses on advances in current and novel oral treatment approaches in MS. We summarily review the oral compounds in this study, focusing on the recent development, approval, and the clinical experience with fingolimod. Keywords: multiple sclerosis, oral compounds, fingolimod, sphingosine-1-phosphate, patient satisfaction, adherence

Demyelination versus remyelination in progressive multiple sclerosis

DEFF Research Database (Denmark)

Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

2010-01-01

The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

A Case of Multiple Sclerosis and Celiac Disease

Directory of Open Access Journals (Sweden)

H. Z. Batur-Caglayan

2013-01-01

Full Text Available Objectives. Multiple sclerosis (MS is an inflammatory autoimmune disorder of the central nervous system (CNS. Since a correlation between gluten intake and incidence of MS had been reported, the relationship of antigliadin antibodies and MS was debated. Case Report. We report the case of a 45-year-old female MS patient who is under interferon treatment. After seven years of monitoring, during her routine gastroenterological assessment, she was diagnosed with celiac disease. Conclusion. Beside the neurological manifestations that have been demonstrated in about 10% of celiac disease (CD patients, white-matter abnormalities in brain MRI are uncommon and controversial. But in the literature, MS seems to be associated with CD as in our patient. We suggest that MS patients with gastroenterological complaints should undergo an assessment for CD.

Literature systematic review on the ophthalmological side effects of interferons

Directory of Open Access Journals (Sweden)

Yara Dadalti Fragoso

2011-08-01

Full Text Available Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.

T-cell homeostasis in chronic HCV-infected patients treated with interferon and ribavirin or an interferon-free regimen

DEFF Research Database (Denmark)

Hartling, Hans Jakob; Birch, Carsten; Gaardbo, Julie C

2015-01-01

Direct-acting antiviral has replaced pegylated interferon-α and ribavirin-based treatment in the treatment of chronic hepatitis C virus (HCV) infection. While interferon-α is immune modulating and causes lymphopenia, interferon-free regimens seem to be well-tolerated. This study aimed to compare T......-cell homeostasis before, during, and after HCV treatment with or without interferon-α in patients with chronic HCV infection. A total of 20 patients with chronic HCV infection were treated with pegylated interferon-α and ribavirin, and six patients were treated with an interferon-free regimen. All patients were...... compared to prior treatment values. Finally, a proportion of CD8+ effector memory was lower while proportion of apoptotic T cells was higher after sustained virologic response compared to prior treatment. Despite lymphopenia during interferon, alterations in T-cell homeostasis during treatment were...

Multiple Sclerosis

Science.gov (United States)

Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

Specificity, cross-talk and adaptation in Interferon signaling

Science.gov (United States)

Zilman, Anton

Innate immune system is the first line of defense of higher organisms against pathogens. It coordinates the behavior of millions of cells of multiple types, achieved through numerous signaling molecules. This talk focuses on the signaling specificity of a major class of signaling molecules - Type I Interferons - which are also used therapeutically in the treatment of a number of diseases, such as Hepatitis C, multiple sclerosis and some cancers. Puzzlingly, different Interferons act through the same cell surface receptor but have different effects on the target cells. They also exhibit a strange pattern of temporal cross-talk resulting in a serious clinical problem - loss of response to Interferon therapy. We combined mathematical modeling with quantitative experiments to develop a quantitative model of specificity and adaptation in the Interferon signaling pathway. The model resolves several outstanding experimental puzzles and directly affects the clinical use of Type I Interferons in treatment of viral hepatitis and other diseases.

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

LENUS (Irish Health Repository)

Saidha, S

2012-01-31

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

LENUS (Irish Health Repository)

Saidha, S

2010-05-01

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

Multiple Sclerosis: Can It Cause Seizures?

Science.gov (United States)

... multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic seizures are more common in ... controlled with anti-seizure medication. With B Mark Keegan, M.D. Lund C, et al. Multiple sclerosis ...

Suicide among Danes with multiple sclerosis

DEFF Research Database (Denmark)

Brønnum-Hansen, H; Stenager, E; Nylev Stenager, E

2005-01-01

OBJECTIVE: To compare the suicide risk among Danish citizens with multiple sclerosis with that of the general population, and to evaluate changes over 45 years. METHODS: The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry. It comprised all 10...... taken their own lives, whereas the expected number of suicides was 54.2 (29.1 men, 25.1 women). Thus the suicide risk among persons with multiple sclerosis was more than twice that of the general population (SMR = 2.12). The increased risk was particularly high during the first year after diagnosis (SMR...... = 3.15). CONCLUSIONS: The risk of suicide in multiple sclerosis was almost twice as high as expected more than 20 years after diagnosis. The excess suicide risk has not declined since 1953....

SUMMIT (Serially Unified Multicenter Multiple Sclerosis Investigation): creating a repository of deeply phenotyped contemporary multiple sclerosis cohorts.

Science.gov (United States)

Bove, Riley; Chitnis, Tanuja; Cree, Bruce Ac; Tintoré, Mar; Naegelin, Yvonne; Uitdehaag, Bernard Mj; Kappos, Ludwig; Khoury, Samia J; Montalban, Xavier; Hauser, Stephen L; Weiner, Howard L

2017-08-01

There is a pressing need for robust longitudinal cohort studies in the modern treatment era of multiple sclerosis. Build a multiple sclerosis (MS) cohort repository to capture the variability of disability accumulation, as well as provide the depth of characterization (clinical, radiologic, genetic, biospecimens) required to adequately model and ultimately predict a patient's course. Serially Unified Multicenter Multiple Sclerosis Investigation (SUMMIT) is an international multi-center, prospectively enrolled cohort with over a decade of comprehensive follow-up on more than 1000 patients from two large North American academic MS Centers (Brigham and Women's Hospital (Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB; BWH)) and University of California, San Francisco (Expression/genomics, Proteomics, Imaging, and Clinical (EPIC))). It is bringing online more than 2500 patients from additional international MS Centers (Basel (Universitätsspital Basel (UHB)), VU University Medical Center MS Center Amsterdam (MSCA), Multiple Sclerosis Center of Catalonia-Vall d'Hebron Hospital (Barcelona clinically isolated syndrome (CIS) cohort), and American University of Beirut Medical Center (AUBMC-Multiple Sclerosis Interdisciplinary Research (AMIR)). We provide evidence for harmonization of two of the initial cohorts in terms of the characterization of demographics, disease, and treatment-related variables; demonstrate several proof-of-principle analyses examining genetic and radiologic predictors of disease progression; and discuss the steps involved in expanding SUMMIT into a repository accessible to the broader scientific community.

Survey of diagnostic and treatment practices for multiple sclerosis in Europe

DEFF Research Database (Denmark)

Fernández, O; Delvecchio, M; Edan, G

2017-01-01

BACKGROUND AND PURPOSE: Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice...... syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. RESULTS: Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat...... a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. CONCLUSIONS...

Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

NARCIS (Netherlands)

van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

2010-01-01

A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

Laboratory diagnosis of multiple sclerosis

International Nuclear Information System (INIS)

Sand, T.; Stovner, L.J.; Rinck, P.A.; Nilsen, G.; Romslo, I.

1991-01-01

In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically ''possible'' or ''probable''multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. The authors recommend that the magnetic resonance imaging is established as a first-hand investigation in evaluation of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine. 23 refs., 2 figs., 2 tabs

Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

Science.gov (United States)

Røsjø, Egil; Myhr, Kjell-Morten; Løken-Amsrud, Kristin Ingeleiv; Bakke, Søren Jacob; Beiske, Antonie G; Bjerve, Kristian S; Hovdal, Harald; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Benth, Jūratė Saltytė; Torkildsen, Øivind; Wergeland, Stig; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Holmøy, Trygve

2014-06-15

To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-β1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-β1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-β1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-β1a treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

Science.gov (United States)

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

Fingolimod Prescribed for the Treatment of Multiple Sclerosis in Patients Younger Than Age 18 Years.

Science.gov (United States)

Fragoso, Yara Dadalti; Alves-Leon, Soniza Vieira; Barreira, Amilton Antunes; Callegaro, Dagoberto; Brito Ferreira, Maria Lucia; Finkelsztejn, Alessandro; Gomes, Sidney; Magno Goncalves, Marcus Vinicius; Moraes Machado, Maria Iris; Marques, Vanessa Daccach; Cunha Matta, Andre Palma; Papais-Alvarenga, Regina Maria; Apostolos Pereira, Samira Luisa; Tauil, Carlos Bernardo

2015-08-01

There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuromyelitis optica-like pathology is dependent on type I interferon response.

Science.gov (United States)

Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin; Owens, Trevor

2013-09-01

Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in the formation of neuromyelitis optica lesions. Immunoglobulin G from a neuromyelitis optica patient was injected intracerebrally with human complement to type I interferon receptor deficient and wildtype mice. Loss of aquaporin-4 and glial fibrillary acidic protein was reduced in type I interferon receptor deficient mice brain. Our findings suggest that type I interferon signaling contributes to neuromyelitis optica pathogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

[Monoclonal antibodies for the treatment of multiple sclerosis].

Science.gov (United States)

Sánchez-Seco, Victoria Galán; Casanova Peño, Ignacio; Arroyo González, Rafael

2014-12-01

Until the mid 1990s, with the appearance of interferon beta and glatiramer acetate, there was no treatment for multiple sclerosis (MS). However, due to their moderate therapeutic potential in some patients, a broad search was continued to find new and more effective treatment strategies, largely concentrated on monoclonal antibodies (MOAB). Natalizumab, the first MOAB for the treatment of MS, was approved at the end of 2004, representing a major advance in the field of neuroimmunology. Today, there is broad experience with natalizumab and other MOAB (alemtuzumab, daclizumab, rituximab, ocrelizumab, ofatumumab and anti-lingo-1) that are pending commercialization or are under phase II or III of development with promising results. The present review analyzes the efficacy and safety results of all these drugs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

PEGylated interferon beta-1a in the treatment of multiple sclerosis – an update

Directory of Open Access Journals (Sweden)

Reuss R

2013-05-01

Full Text Available Reinhard ReussDepartment of Neurology, BKH Bayreuth, Bayreuth, GermanyAbstract: Current standard immunomodulatory therapy with interferons (IFNs for relapsing–remitting multiple sclerosis (MS exhibits proven, but limited, efficacy and increased side effects due to the need of frequent application of the drug. Therefore, there is a need for more effective and tolerable drugs. Due to their small size, optimization of therapy with IFNs in MS by PEGylation is feasible. PEGylation of an IFN means that at least one molecule of polyethylene glycol (PEG is covalently added. This modification is a standard procedure to increase the stability, solubility, half-life, and efficacy of a drug, and is applied in several drugs and diseases. Currently, a therapy regimen applying PEG-IFN beta-1a in MS is being developed to achieve an optimized relationship between therapy-related side effects and pharmacokinetic/pharmacodynamic efficacy. Phase I studies demonstrated that subcutaneous PEG-IFN beta-1a at a dose of 125 µg every 2 or 4 weeks might be at least as efficient and safe as the current standard therapy with IFN beta-1a. A global Phase III clinical study is investigating the efficacy of PEG-IFN beta-1a in terms of reduction of the relapse rate in relapsing–remitting MS patients. The latest primary safety and efficacy analysis after 1 year has revealed a favorable risk–benefit profile with no significant difference between dosing regimens. Compared to placebo, the annualized relapse rate was reduced by about one-third and new or newly enlarging T2 brain lesions were reduced by about one-third when dosing every 4 weeks or by two-thirds when dosing every 2 weeks. This presents a significant effect of the dosing interval, favoring administration every 2 weeks. Chronic administration of PEGylated proteins mostly at toxic concentrations causes vacuolation of renal epithelium in animals, which – along with the issue of occurrence of anti-PEG antibodies �

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

Directory of Open Access Journals (Sweden)

Julie Chevalier

Full Text Available The paper aimed to estimate the incremental cost-effectiveness ratio (ICER at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015.The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results.From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY of 0.281, corresponding to an ICER of €13,110/QALY.Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

Science.gov (United States)

Chevalier, Julie; Chamoux, Catherine; Hammès, Florence; Chicoye, Annie

2016-01-01

The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

Epidemiological study of multiple sclerosis in La Rioja.

Science.gov (United States)

Bártulos Iglesias, M; Marzo Sola, M E; Estrella Ruiz, L A; Bravo Anguiano, Y

2015-01-01

Multiple sclerosis is a demyelinating disease that causes severe disability in younger patients. Many epidemiology studies have confirmed a variable prevalence. The objective of this study was to analyse the prevalence of this disease in La Rioja (Spain), using such variables as age and sex; type of progression, initial form of the disease, EDSS and number of relapses; disease-modifying treatment and reasons for treatment withdrawal; personal and family history of cancer; and incidence and mortality. Analysis of patients in La Rioja diagnosed with MS (according to Poser criteria or the 2005 McDonald criteria) during a 10-year period (2001-2011). Data were collected from hospital records, multiple sclerosis associations, and personal records kept by neurologists. The MS prevalence rate in La Rioja is 65 patients/100 000 inhabitants with an incidence rate of 3.5 cases/100 000 residents per year. Relapsing-remitting MS is present in 67.6% of the patient total. Mean age of onset is 20-29 years (range, 12 to 70). Most EDSS scores were mostly ≤ 2. Untreated MS cases account for 47.6% of the total and the most commonly used therapy is interferon. We detected 4 haematological tumours and 7 families with multiple members affected by MS. Prevalence and incidence are similar to those found in other regions Spain. The average age at onset age for primary progressive MS is slightly higher than in other papers (40-49 years). In families with multiple patients, MS may be more aggressive. Disability in these patients remains very severe. We require more epidemiology studies with a variety of data gathering methods to support findings for prevalence obtained in different provinces. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

The Effect of Levothyroxine on Serum Levels of Interleukin 10 and Interferon-gamma in Rat Model of Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Cobra Payghani

2017-01-01

Full Text Available Background: There is an increase in inflammatory and a reduction in anti-inflammatory cytokines in multiple sclerosis (MS. Considering the role of thyroid hormones in the development and regulation of both neural and immune systems, the aim of this study was to evaluate the effects of levothyroxine on serum concentrations of interleukin-10 (IL-10 and interferon gamma (IFN-γ in animal models of MS. Materials and Methods: To induce demyelination in male Wistar rats, lysolecithin was injected into the optic chiasm. Then levothyroxine was injected intraperitoneally (20, 50, and 100 μg/kg for 21 days. Serum levels of cytokines were measured by enzyme-linked immunosorbent assay at 7, 14, and 21 days after that. Results: The results showed that injection of lysolecithin to the optic chiasm only increased serum concentrations of IL-10 compared to the sham group (P < 0.05 at 7th day, but this increase was prevented by all doses of levothyroxine. IFN-γ was decreased significantly (P < 0.001 21 days after. Comparing to the sham group at all sampling time and with respect to the MS group at the days 7 and 21, levothyroxine decreased serum concentrations of IFN-γ significantly. Conclusion: The results showed that thyroid hormones probably could produce protective effects against induced demyelination through affecting immune responses.

Safety concerns and risk management of multiple sclerosis therapies

DEFF Research Database (Denmark)

Soelberg Sorensen, P.

2017-01-01

Currently, more than ten drugs have been approved for treatment of relapsing-remitting multiple sclerosis (MS). Newer treatments may be more effective, but have less favorable safety record. Interferon-β preparations and glatiramer acetate treatment require frequent subcutaneous or intramuscular...... disease activity can choose between dimethyl fumarate and teriflunomide or the “old injectable.” Patients with very active MS may choose a more effective drug as the initial treatment. In case of side effects on one drug, switch to another drug can be tried. Suboptimal effect of the first drug indicates...... escalation to a highly efficacious drug. A favorable benefit-risk balance can be maintained by appropriate patient selection and appropriate risk management on therapy. New treatments will within the coming 1-2 years change our current treatment algorithm for relapsing-remitting MS....

Pregnancy and the Use of Disease-Modifying Therapies in Patients with Multiple Sclerosis: Benefits versus Risks

Directory of Open Access Journals (Sweden)

Raed Alroughani

2016-01-01

Full Text Available The burden of multiple sclerosis (MS in women of childbearing potential is increasing, with peak incidence around the age of 30 years, increasing incidence and prevalence, and growing female : male ratio. Guidelines recommend early use of disease-modifying therapies (DMTs, which are contraindicated or recommended with considerable caution, during pregnancy/breastfeeding. Many physicians are reluctant to prescribe them for a woman who is/is planning to be pregnant. Interferons are not absolutely contraindicated during pregnancy, since interferon-β appears to lack serious adverse effects in pregnancy, despite a warning in its labelling concerning risk of spontaneous abortion. Glatiramer acetate, natalizumab, and alemtuzumab also may not induce adverse pregnancy outcomes, although natalizumab may induce haematologic abnormalities in newborns. An accelerated elimination procedure is needed for teriflunomide if pregnancy occurs on treatment or if pregnancy is planned. Current evidence supports the contraindication for fingolimod during pregnancy; data on other DMTs remains limited. Increased relapse rates following withdrawal of some DMTs in pregnancy are concerning and require further research. The postpartum period brings increased risk of disease reactivation that needs to be carefully addressed through effective communication between treating physicians and mothers intending to breastfeed. We address the potential for use of the first- and second-line DMTs in pregnancy and lactation.

Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

Directory of Open Access Journals (Sweden)

Necla Keskin

2013-08-01

Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

Multiple sclerosis in Latter Day Saints (Mormons).

Science.gov (United States)

Hawkes, C H; Ramkumar, N; Baker, R; Lyon, J L

2007-04-01

Compliant members of the Church of Jesus Christ of Latter Day Saints (LDS, Mormons) have a low incidence of heart and lung disease that may relate to their healthy life style. We wished to determine whether multiple sclerosis (MS) was less frequent in this religious body. To ascertain this, diagnostic and treatment coding records were accessed from the Deseret Mutual Benefit Administrators (DMBA) for the 6 year period 1997-2002. DMBA is a medical insurance company that provides medical insurance to all employees of LDS Church in the US. This information was combined with prescribing records for disease modifying treatment, principally beta-interferon and Copaxone which are medications specific to MS. Using various search strategies we derived an approximate MS prevalence of 45-64/100,000. Comparison with MS rates from Utah and other states of comparable latitude suggest that strict LDS have an MS prevalence that is lower than expected and may reflect their healthy life style.

Gait Characteristics in Adolescents With Multiple Sclerosis.

Science.gov (United States)

Kalron, Alon; Frid, Lior; Menascu, Shay

2017-03-01

Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1991-01-01

In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Jensen, K

1990-01-01

An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

Multiple sclerosis - etiology and diagnostic potential.

Science.gov (United States)

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Multiple sclerosis - etiology and diagnostic potential

Directory of Open Access Journals (Sweden)

Joanna Kamińska

2017-06-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Product related factors influencing the immunogenicity of interferon beta-1b

NARCIS (Netherlands)

Haji Abdolvahab, M.

2016-01-01

Therapeutic interferon beta is the first line treatment of relapsing remitting Multiple Sclerosis. However, despite their success in improving patient wellbeing, all IFNβ products encounter a significant problem: immunogenicity. In some patients, IFNβ products induce the formation of antidrug

Understanding and meeting injection device needs in multiple sclerosis: a survey of patient attitudes and practices

Science.gov (United States)

Verdun di Cantogno, Elisabetta; Russell, Susan; Snow, Tom

2011-01-01

Background: All established disease-modifying drugs for multiple sclerosis require parenteral administration, which can cause difficulties for some patients, sometimes leading to suboptimal adherence. A new electronic autoinjection device has been designed to address these issues. Methods: Patients with relapsing multiple sclerosis currently receiving subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, or glatiramer acetate completed an online questionnaire (July 4–25, 2008) that surveyed current injection practices, experiences with current injection methods, and impressions and appeal of the new device. Results: In total, 422 patients completed the survey, of whom 44% used autoinjectors, 43% prefilled syringes, and 13% syringes and vials; overall, 66% currently self-injected. Physical and psychological barriers to self-injection included difficulty with injections, needle phobia, and concerns over correct injection technique. Only 40% of respondents were “very satisfied” with their current injection method. The new electronic autoinjector was rated as “very appealing” by 65% of patients. The benefits of the new device included the ability to customize injection settings and to review dosing history. Conclusion: New technologies may help patients overcome physical and psychological barriers to self-injection. The combination of a reliable and flexible autoinjection device with dose-monitoring technology may improve communication between health care professionals and patients, and improve treatment adherence. PMID:21573048

Activation of endogenous neural stem cells for multiple sclerosis therapy

NARCIS (Netherlands)

Michailidou, I.; de Vries, H.E.; Hol, E.M.; van Strien, M.E.

2015-01-01

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Jensen, K

1988-01-01

Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

Primary progressive multiple sclerosis in the Polish population

Directory of Open Access Journals (Sweden)

Waldemar Brola

2017-03-01

Full Text Available Objectives: The aim of the study was the epidemiological analysis and evaluation of selected clinical and sociodemographic factors in Polish patients with primary progressive multiple sclerosis. Methods: The study included patients from 7 provinces in central and eastern Poland registered in the Registry of Patients with Multiple Sclerosis on 31 December 2016. The incidence of various forms of the disease was compared, and clinical, demographic and social disparities between relapsing-remitting and primary progressive multiple sclerosis were analysed. Results: Of 3,199 registered patients, 2,188 persons (66.2% had the relapsing-remitting form of multiple sclerosis, 774 (24.2% had the secondary progressive type and 307 (9.6% suffered from primary progressive disease. The first symptoms of primary progressive multiple sclerosis appeared almost 10 years later than in patients with the relapsing-remitting type (39.2 ± 11.4 vs. 29.8 ± 9.8. The period from the first symptoms to diagnosis was more than twice as long in patients with primary progressive multiple sclerosis (5.8 ± 3.4 as in those with relapsing-remitting disease (2.4 ± 1.6. The average degree of disability in the Expanded Disability Status Scale was similar and amounted to 3.2 ± 2.1 for relapsing-remitting and 3.6 ± 2.4 for primary progressive multiple sclerosis. The relapsing-remitting form was observed more often in women (2.4:1, and the primary progressive form appeared with equal frequency in both sexes (1:1. Disease-modifying treatment was received by 34% of patients with relapsing-remitting and in only 1.9% of patients with primary progressive multiple sclerosis. Conclusions: The primary progressive form affects approximately 10% of Polish patients with multiple sclerosis. The first symptoms appear at about 40 years of age with equal frequency in both sexes, and its diagnosis takes more than twice as much time as in the case of relapsing-remitting multiple

Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

International Nuclear Information System (INIS)

Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

2010-01-01

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

Emotional Disorders in People with Multiple Sclerosis

Science.gov (United States)

... Evidence-based Guideline for PATIENTS and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the ...

Multiple Sclerosis.

Science.gov (United States)

Plummer, Nancy; Michael, Nancy, Ed.

This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

Multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E; Knudsen, L; Jensen, K

1994-01-01

In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis

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Prais Wes A

2008-10-01

Full Text Available Abstract Background To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G], sharper (5-bevel needle than the 27G/3-bevel needle used previously to inject interferon (IFN beta-1a, 44 or 22 mcg subcutaneously (sc three times weekly (tiw, was developed for use in multiple sclerosis (MS. Methods Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE needle shield (a sleeve that houses the tip of the needle in a secure location is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales; and patient satisfaction (surveys of patients with MS. Results In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS and Verbal VAS (VB-VAS; mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p Conclusion Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw.

Multiple sclerosis research

International Nuclear Information System (INIS)

Battaglia, M.A.

1990-01-01

This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

Directory of Open Access Journals (Sweden)

Gajofatto A

2015-12-01

Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

Progression of regional grey matter atrophy in multiple sclerosis.

Science.gov (United States)

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple

Progression of regional grey matter atrophy in multiple sclerosis

Science.gov (United States)

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse

Nuclear magnetic resonance relaxation in multiple sclerosis

DEFF Research Database (Denmark)

Larsson, H B; Barker, G J; MacKay, A

1998-01-01

OBJECTIVES: The theory of relaxation processes and their measurements are described. An overview is presented of the literature on relaxation time measurements in the normal and the developing brain, in experimental diseases in animals, and in patients with multiple sclerosis. RESULTS...... AND CONCLUSION: Relaxation time measurements provide insight into development of multiple sclerosis plaques, especially the occurrence of oedema, demyelination, and gliosis. There is also evidence that normal appearing white matter in patients with multiple sclerosis is affected. What is now needed are fast...

Sodium intake and multiple sclerosis activity and progression in BENEFIT

DEFF Research Database (Denmark)

Fitzgerald, Kathryn C; Munger, Kassandra L; Hartung, Hans-Peter

2017-01-01

OBJECTIVE: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. METHODS: BENEFIT was a randomized clinical trial comparing early versus...... delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether...... in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. INTERPRETATION: Our results, based on multiple assessments of urine sodium excretion over 5...

Registers of multiple sclerosis in Denmark

DEFF Research Database (Denmark)

Koch-Henriksen, N; Magyari, M; Laursen, B

2015-01-01

between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have......There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS....

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

Science.gov (United States)

Bernstock, Joshua D.; Pluchino, Stefano

2015-01-01

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis. PMID:25802011

Patient assessment of an electronic device for subcutaneous self-injection of interferon ß-1a for multiple sclerosis: an observational study in the UK and Ireland

Directory of Open Access Journals (Sweden)

D'Arcy C

2012-01-01

Full Text Available Caroline D’Arcy1, Del Thomas2, Dee Stoneman3, Laura Parkes31West London Neuroscience Centre, Charing Cross Hospital, London, UK; 2Wye Valley NHS Trust, Hereford, UK; 3Merck Serono Ltd, Feltham, Middlesex, UKBackground: Injectable disease-modifying drugs (DMDs reduce the number of relapses and delay disability progression in patients with relapsing–remitting multiple sclerosis (RRMS. Regular self-injection can be stressful and impeded by MS symptoms. Auto-injection devices can simplify self-injection, overcome injection-related issues, and increase treatment satisfaction. This study investigated patient responses to an electronic auto-injection device.Methods: Patients with RRMS (n = 63, aged 18–65 years, naïve to subcutaneous (sc interferon (IFN ß-1a therapy, were recruited to a Phase IV, observational, open-label, multicenter study (NCT01195870. Patients self-injected sc IFN ß-1a using the RebiSmart™ (Merck Serono S.A. – Geneva, Switzerland electronic auto-injector for 12 weeks, including an initial titration period if recommended by the prescribing physician. In week 12, patients completed a questionnaire comprising of a visual analog scale (VAS to rate how much they liked using the device, a four-point response question on ease of use (‘very difficult’, ‘difficult’, ‘easy’, or ‘very easy’, and a list of ten device functions to rank, based upon their experiences.Results: Six patients (9.5% discontinued the study: one switched to manual injection; two discontinued all treatment; three changed therapy. In total, 59 out of 63 patients (93.7% completed the VAS; 54 out of 59 (91.5%; 95% confidence interval: 81.3%–97.2% ‘liked’ using the electronic auto-injector (score ≥6, whereas 57 out of 59 (96.6% rated the device overall as ‘easy’ or ‘very easy’ to use. Device features rated as most useful were the hidden needle (mean [standard deviation] score: 3.3 [3.01]; n = 56, confirmation sound (3.9 [2.45], and

Reproduction and the risk of multiple sclerosis

DEFF Research Database (Denmark)

Magyari, Melinda; Koch-Henriksen, Nils Iørgen; Pfleger, Claudia Christina

2013-01-01

The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men.......The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men....

Multiple sclerosis: New insights and trends

Directory of Open Access Journals (Sweden)

Khaled Mohamed Mohamed Koriem

2016-05-01

Full Text Available Multiple sclerosis (MS is the most famous autoimmune disease attacking the central nervous system. It attacks people from age 20–50 years old and the females' attacks double than males' attacks. MS is an autoimmune disease affecting principally the central nervous system that cause nerve sheath demyelination followed by axon damage and paralysis. MS symptoms include muscle weakness, weak reflexes, muscle spasm, difficult in move, miss-coordination and unbalance with others. There are many factors may be responsible for MS: microbial, viral, smoking, stress, environmental toxins, contaminated diet, and gout. MS is wide spread in the populations in North Europe and this related to lack of vitamin D due to decrease of sunlight exposure. MS biomarkers include nitric oxide, interleukin-6, nitric oxide synthase, fetuin-A and osteopontin. MS is not a genetic disease where MS occurs when human leukocyte antigen system related genes are changed in chromosome 6. The physiology of MS is monitored by activation of immune-inflammatory, oxidative, and nitrosative stress pathways. MS is including two main steps: (1 myelin sheath destruction and formation of lesions and, (2 inflammation. Four types of MS can be distinguished: relapsing-remitting, primary progressive, secondary progressive and progressive relapsing. Nine treatments have been accepted for relapsing-remitting MS type: interferon β-1a, interferon β-1b, mitoxantrone, natalizumab, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab, however, the only treatment used is mitoxantrone for progressive MS but many of MS treatments side effects are recorded. Complementary treatments also used in MS treatments such as: vitamin D, Yoga, medicinal plants, oxygen therapy, acupuncture and reflexology.

The management of multiple sclerosis in children: a European view

DEFF Research Database (Denmark)

Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce...... in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.......About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity...

Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Burcu Altunrende

2017-12-01

Full Text Available Multiple sclerosis (MS is a chronic autoimmune disease of the central nervous system and is characterized by inflammation, demyelination, and axonal loss. Fingolimod is the first oral drug for the treatment of MS approved by the United States Food and Drug Administration, European Union countries, and various other countries. The compound exerts its effect via interaction with lysophospholipid receptors known as sphingosine-1 phosphate receptors. Although fingolimod has a very convenient daily oral dosing, it may cause development of bradycardia at the first dose, macular edema, infection, all of which require attention. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rates and is beneficial in brain magnetic resonance imaging measures when compared with both placebo and intramuscular interferon β-1a. This review describes the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of the management of MS

Impact of natalizumab on ambulatory improvement in secondary progressive and disabled relapsing-remitting multiple sclerosis.

Directory of Open Access Journals (Sweden)

Diego Cadavid

Full Text Available There is an unmet need for disease-modifying therapies to improve ambulatory function in disabled subjects with multiple sclerosis.Assess the effects of natalizumab on ambulatory function in disabled subjects with relapsing-remitting multiple sclerosis (RRMS or secondary progressive multiple sclerosis (SPMS.We retrospectively reviewed ambulatory function as measured by timed 25-foot walk (T25FW in clinical trial subjects with an Expanded Disability Status Scale score ≥3.5, including RRMS subjects from the phase 3 AFFIRM and SENTINEL trials, relapsing SPMS subjects from the phase 2 MS231 study, and nonrelapsing SPMS subjects from the phase 1b DELIVER study. For comparison, SPMS subjects from the intramuscular interferon beta-1a (IM IFNβ-1a IMPACT study were also analyzed. Improvement in ambulation was measured using T25FW responder status; response was defined as faster walking times over shorter (6-9-month or longer (24-30-month treatment periods relative to subjects' best predose walking times.There were two to four times more T25FW responders among disabled MS subjects in the natalizumab arms than in the placebo or IM IFNβ-1a arms. Responders walked 25 feet an average of 24%-45% faster than nonresponders.Natalizumab improves ambulatory function in disabled RRMS subjects and may have efficacy in disabled SPMS subjects. Confirmation of the latter finding in a prospective SPMS study is warranted.

Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

International Nuclear Information System (INIS)

Mameli, Giuseppe; Astone, Vito; Khalili, Kamel; Serra, Caterina; Sawaya, Bassel E.; Dolei, Antonina

2007-01-01

Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFα, interferon-γ, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-β is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFα had the ability to activate the ERVWE1 promoter through an NF-κB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFα enhances the binding of the p65 subunit of NF-κB, to its cognate site within the promoter. The effect of TNFα is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFα-mediated induction of syncytin-1 in multiple sclerosis

A randomized crossover study of bee sting therapy for multiple sclerosis

NARCIS (Netherlands)

Wesselius, T; Heersema, DJ; Mostert, JP; Heerings, M; Admiraal-Behloul, F; Talebian, A; van Buchem, MA; De Keyser, J

2005-01-01

Background: Bee sting therapy is increasingly used to treat patients with multiple sclerosis (MS) in the belief that it can stabilize or ameliorate the disease. However, there are no clinical studies to justify its use. Methods: In a randomized, crossover study, we assigned 26 patients with

Can aerobic exercise alleviate flu-like symptoms following interferon beta-1a injections in patients with multiple sclerosis?

DEFF Research Database (Denmark)

Langeskov-Christensen, Martin; Kjølhede, Tue; Stenager, Egon

2016-01-01

IFNß-1a injections in persons with multiple sclerosis (PwMS). OBJECTIVE: To test the hypothesis that aerobic exercise can alleviate FLS following IFNß-1a injections in PwMS, and secondarily to examine whether or not fluctuations in circulating cytokines provide a mechanism that can explain a potential...

Demyelination of subcortical nuclei in multiple sclerosis

Science.gov (United States)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

Science.gov (United States)

Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

2017-12-01

To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Multiple sclerosis influences on the augmentation of serum Klotho concentration

DEFF Research Database (Denmark)

Ahmadi, Mona; Aleagha, Mohammad Sajad Emami; Harirchian, Mohammad Hossein

2016-01-01

We have already shown that the concentration of secreted form of Klotho decreases in the cerebrospinal fluid of patients with relapsing–remitting multiple sclerosis (RRMS). The current study aimed at assessing possible changes in the serum Klotho concentration of MS patients. Participants involved...... 15 new cases of RRMS patients in the relapse phase, 15 RRMS patients who had been suffering from the disease for more than three years and were under regular treatments (interferon beta-1a) and, finally, 15 non-MS patients who constituted the control group. Beside thorough neurological examinations...... to be higher in MS patients when compared to control group. This finding might be attributed to treatment of MS patients with immunomodulatory drugs or a compensatory response to enhance CNS regeneration and/or vitamin D biosynthesis. Further studies are required to elucidate the role of Klotho in MS...

Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis

DEFF Research Database (Denmark)

Krakauer, Martin; Sorensen, P; Khademi, M

2008-01-01

BACKGROUND: Interferon (IFN)-beta therapy in multiple sclerosis (MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell (MNC...... of any Th1 or Th2 cytokines. The largest changes in cytokine mRNA levels occurred early (~9-12 h) after an IFN-beta injection. CONCLUSION: We found no evidence of a Th1- or Th2-mRNA-promoting effect of IFN-beta therapy. The therapeutic effect of IFN-beta is more likely attributable to the induction...

Demyelination of subcortical nuclei in multiple sclerosis

International Nuclear Information System (INIS)

Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

2016-01-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

Retinal layer segmentation in multiple sclerosis

DEFF Research Database (Denmark)

Petzold, Axel; Balcer, Laura J; Calabresi, Peter A

2017-01-01

BACKGROUND: Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal...... layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. METHODS: In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people...... with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified...

Serum total antioxidant capacity in patients with multiple sclerosis

Directory of Open Access Journals (Sweden)

Almira Hadžović-Džuvo

2011-02-01

Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system (CNS. It is characterized by loss of myelin, the fatty tissue that surrounds and protects nerve fibres allowing them to conduct electrical impulses. Recent data indicate that oxidative stress (OS plays a major role in the pathogenesis of multiple sclerosis (MS. The aim of this study was to estimate level of serum total antioxidative capacity in patients with multiple sclerosis. Our cross-sectional study included 33 patients with MS and 24 age and sex matched control subjects. All our patients had a Poser criteria for definite diagnostic categories of multiple sclerosis. Serum total antioxidant capacity (TAC was measured by quantitative colorimetric determination, using Total antioxidant Capacity-QuantiCromAntioxidant Assay Kit (BioAssay systems, USA; DTAC-100. Mean serum TAC in multiple sclerosis group of patients was 119.2 mM Trolox equivalents and was significantly lower (p<0.001 compared to the control group of subjects (167.1 mM Trolox equivalents. Our results showed that oxidative stress plays an important role in pathogenesis of multiple sclerosis. This finding, also, suggests the importance of antioxidants in diet and therapy of MS patients.

Symptomatic Epstein-Barr virus infection and multiple sclerosis.

OpenAIRE

Martyn, C N; Cruddas, M; Compston, D A

1993-01-01

In a case-control study of 214 patients with multiple sclerosis, recall of infectious mononucleosis in subjects seropositive for Epstein-Barr viral capsid antigen was associated with a relative risk of 2.9 (95% CI 1.1 to 7.2). Those who reported having infectious mononucleosis before the age of 18 years had a relative risk of multiple sclerosis of 7.9 (95% CI 1.7 to 37.9). The pathogenesis of multiple sclerosis may involve an age-dependent host response to Epstein-Barr virus infection.

The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

Science.gov (United States)

Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

2015-01-01

Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

Neuraxial anesthesia in patients with multiple sclerosis - a systematic review

Directory of Open Access Journals (Sweden)

Helmar Bornemann-Cimenti

Full Text Available Abstract Background and objectives: Current guidelines for neuraxial analgesia in patients with multiple sclerosis are ambiguous and offer the clinician only a limited basis for decision making. This systematic review examines the number of cases in which multiple sclerosis has been exacerbated after central neuraxial analgesia in order to rationally evaluate the safety of these procedures. Methods: A systematic literature search with the keywords "anesthesia or analgesia" and "epidural, peridural, caudal, spinal, subarachnoid or intrathecal" in combination with "multiple sclerosis" was performed in the databases PubMed and Embase, looking for clinical data on the effect of central neuraxial analgesia on the course of multiple sclerosis. Results and conclusions: Over a period of 65 years, our search resulted in 37 reports with a total of 231 patients. In 10 patients multiple sclerosis was worsened and nine multiple sclerosis or neuromyelitis optica was first diagnosed in a timely context with central neuraxial analgesia. None of the cases showed a clear relation between cause and effect. Current clinical evidence does not support the theory that central neuraxial analgesia negatively affects the course of multiple sclerosis.

Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity

DEFF Research Database (Denmark)

Hesse, D.; Sellebjerg, F.; Sorensen, P.S.

2009-01-01

BACKGROUND: In patients with multiple sclerosis (MS), neutralizing antibodies (NAbs) appearing during treatment with interferon (IFN) beta reduce or in high concentrations abolish bioactivity and therapeutic efficacy. In vivo MxA induction by IFNbeta is used as a marker of biologic response....... Lack of MxA in vivo response in patients with multiple sclerosis with NAbs is a reliable marker of a completely blocked biologic response to IFNbeta, with no indication of residual bioactivity Udgivelsesdato: 2009/8/4...

Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

Science.gov (United States)

Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

2017-03-01

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis; Asociacion de LES y esclerosis multiple: esclerosis lupoide.

Energy Technology Data Exchange (ETDEWEB)

Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

2010-07-01

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

Baseline predictors of persistence to first disease-modifying treatment in multiple sclerosis.

Science.gov (United States)

Zettl, U K; Schreiber, H; Bauer-Steinhusen, U; Glaser, T; Hechenbichler, K; Hecker, M

2017-08-01

Patients with multiple sclerosis (MS) require lifelong therapy. However, success of disease-modifying therapies is dependent on patients' persistence and adherence to treatment schedules. In the setting of a large multicenter observational study, we aimed at assessing multiple parameters for their predictive power with respect to discontinuation of therapy. We analyzed 13 parameters to predict discontinuation of interferon beta-1b treatment during a 2-year follow-up period based on data from 395 patients with MS who were treatment-naïve at study onset. Besides clinical characteristics, patient-related psychosocial outcomes were assessed as well. Among patients without clinically relevant fatigue, males showed a higher persistence rate than females (80.3% vs 64.7%). Clinically relevant fatigue scores decreased the persistence rate in men and especially in women (71.4% and 51.2%). Besides gender and fatigue, univariable and multivariable analyses revealed further factors associated with interferon beta-1b therapy discontinuation, namely lower quality of life, depressiveness, and higher relapse rate before therapy initiation, while higher education, living without a partner, and higher age improved persistence. Patients with higher grades of fatigue and depressiveness are at higher risk to prematurely discontinue MS treatment; especially, women suffering from fatigue have an increased discontinuation rate. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sit less and move more: perspectives of adults with multiple sclerosis.

Science.gov (United States)

Aminian, Saeideh; Ezeugwu, Victor E; Motl, Robert W; Manns, Patricia J

2017-12-20

Multiple sclerosis is a chronic neurological disease with the highest prevalence in Canada. Replacing sedentary behavior with light activities may be a feasible approach to manage multiple sclerosis symptoms. This study explored the perspectives of adults with multiple sclerosis about sedentary behavior, physical activity and ways to change behavior. Fifteen adults with multiple sclerosis (age 43 ± 13 years; mean ± standard deviation), recruited through the multiple sclerosis Clinic at the University of Alberta, Edmonton, Canada, participated in semi-structured interviews. Interview audios were transcribed verbatim and coded. NVivo software was used to facilitate the inductive process of thematic analysis. Balancing competing priorities between sitting and moving was the primary theme. Participants were aware of the benefits of physical activity to their overall health, and in the management of fatigue and muscle stiffness. Due to fatigue, they often chose sitting to get their energy back. Further, some barriers included perceived fear of losing balance or embarrassment while walking. Activity monitoring, accountability, educational and individualized programs were suggested strategies to motivate more movement. Adults with multiple sclerosis were open to the idea of replacing sitting with light activities. Motivational and educational programs are required to help them to change sedentary behavior to moving more. IMPLICATIONS FOR REHABILITATION One of the most challenging and common difficulties of multiple sclerosis is walking impairment that worsens because of multiple sclerosis progression, and is a common goal in the rehabilitation of people with multiple sclerosis. The deterioration in walking abilities is related to lower levels of physical activity and more sedentary behavior, such that adults with multiple sclerosis spend 8 to 10.5 h per day sitting. Replacing prolonged sedentary behavior with light physical activities, and incorporating education

The natural history of primary progressive multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Kingwell, Elaine; Rieckmann, Peter; Tremlett, Helen

2009-01-01

Background: Primary progressive multiple sclerosis (PPMS) carries the worst prognosis of the multiple sclerosis (MS) subtypes and is currently untreatable. A previous analysis of the British Columbia MS database challenged the view that disability progression is rapid in PPMS, but identified few

The Practice of Sport in Multiple Sclerosis: Update.

Science.gov (United States)

Donze, Cecile; Massot, Caroline; Hautecoeur, Patrick; Cattoir-Vue, Helene; Guyot, Marc-Alexandre

The practice of sport by multiple sclerosis patients has long been controversial. Recent studies, however, show that both sport and physical activity are essential for these patients. Indeed, they help to cope with the effects of multiple sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction of muscle strength. The beneficial effects of physical activity on these patients have been underlined in several studies, whereas those of practicing sport have been the subject of fewer evaluations and assessments. The aim of this update is to report on the effects of sport on multiple sclerosis patients. The benefits of sport have been demonstrated in several studies. It helps multiple sclerosis patients to increase their balance, resistance to fatigue, mobility and quality of life. Several biases in these studies do not enable us to recommend the practice of some of these sports on a routine basis.

Multiple sclerosis: current immunological aspects

Directory of Open Access Journals (Sweden)

Carlos Cuevas-García

2017-02-01

Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

Long-term impact of interferon beta-1b in patients with CIS

DEFF Research Database (Denmark)

Edan, G; Kappos, L; Montalbán, X

2014-01-01

OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...

Vitamin D Levels Predict Multiple Sclerosis Progression

Science.gov (United States)

... Research Matters NIH Research Matters February 3, 2014 Vitamin D Levels Predict Multiple Sclerosis Progression Among people ... sclerosis (MS), those with higher blood levels of vitamin D had better outcomes during 5 years of ...

Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, Fingolimod will change therapeutic paradigm approach

Directory of Open Access Journals (Sweden)

Gasperini C

2012-07-01

Full Text Available Claudio Gasperini,1 Serena Ruggieri21Department of Neurosciences, S Camillo Forlanini Hospital, 2Department of Neurology and Psychiatry, University of Rome “Sapienza,” Rome, ItalyAbstract: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.Keywords: multiple sclerosis, oral compounds, fingolimod, fty720, sphingosine 1, phosphate, patient satisfaction

[Disease concept, etiology and mechanisms of multiple sclerosis].

Science.gov (United States)

Kira, Jun-Ichi

2014-11-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system(CNS). MS is assumed to be caused by a complex interplay between genes and environments. Autoimmune mechanisms targeting CNS myelin has long been proposed, yet it has not been proved. Th17 cells producing interleukin-17 and Th1 cells producing interferon-gamma are postulated to play major roles in initiating inflammation while regulatory T cell functions are dampened. The forth nationwide survey of MS in Japan revealed that MS prevalence showed four-folds increase over 30 years and the increase was especially prominent in female. Thus, westernized life style and improved sanitation are suspected to increase MS susceptibility. Genome-wide association studies in Western MS patients disclosed more than 100 disease-susceptibility genes, most of which are immune-related genes. It therefore supports immune-mediated mechanisms to be operative. Detailed magnetic resonance imaging studies revealed an early atrophy of the cerebral gray matter where T cell infiltration is pathologically scarce. Therefore, neurodegenerative process also takes place in the early course beside neuroinflammation.

Risks of multiple sclerosis in relatives of patients in Flanders, Belgium

NARCIS (Netherlands)

Carton, H; Vlietinck, R; Debruyne, J; DeKeyser, J; DHooghe, MB; Loos, R; Medaer, R; Truyen, L; Yee, IML; Sadovnick, AD

Objectives - To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. Methods - Lifetime risks were calculated using the maximum likelihood approach. Results - Vital information was obtained on 674 probands with multiple sclerosis in Flanders

The risk of multiple sclerosis in bereaved parents

DEFF Research Database (Denmark)

Li, J; Johansen, C; Brønnum-Hansen, Henrik

2004-01-01

Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited.......Previous studies have suggested that psychological stress may play a role in the risk of multiple sclerosis (MS), but the evidence is very limited....

Incidence of multiple sclerosis in Denmark 1948-1982

DEFF Research Database (Denmark)

Koch-Henriksen, Nils; Brønnum-Hansen, Henrik; Hyllested, K

1992-01-01

The incidence rates of multiple sclerosis (MS) in Denmark were estimated as a result of a continuous nationwide epidemiological survey since 1948 by the Danish Multiple Sclerosis Registry (DMSR). Among cases notified to the DMSR, 6,478 met the diagnostic criteria and had onset of MS from 1948...

Rehabilitation in multiple sclerosis.

Science.gov (United States)

Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

2017-07-01

The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

Science.gov (United States)

Mackenzie, Catherine; Green, Jan

2009-01-01

Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

Non-invasive examination of multiple sclerosis patients

International Nuclear Information System (INIS)

Weerd, A.W. de.

1981-01-01

Multiple sclerosis is characterized by a wide range of symptoms and, in many cases, by a highly erratic course. As a result diagnosis is often a problem. Two non-invasive examinations, Computer Tomography (CT scan) and the Evoked Response test (ER), are the subjects of this study which, according to available literature, both can play a role in the establishment of the diagnosis of multiple sclerosis. Clinical trials have been performed and both methods demonstrated abnormalities of the central nervous system which were not suspected on clinical grounds; as a result both methods of examination can contribute to the early establishment of the diagnosis of multiple sclerosis. In addition the diagnosis can be determined with greater certainty when the findings of the CT-scan and the evoked response test are taken into consideration. (Auth.)

Spinal-cord swelling in acute multiple sclerosis

International Nuclear Information System (INIS)

Kikuchi, Seiji; Tashiro, Kunio; Naganuma, Mutsuo; Hida, Kazutoshi; Iwasaki, Yoshinobu; Abe, Hiroshi; Miyasaka, Kazuo

1986-01-01

Despite the frequent involvement of the spinal cord by multiple sclerosis, reports concerning neuroradiological findings regarding these lesions have been limited; most of them have demonstrated a normal or small spinal cord. Two cases of acute paraparesis showed evidence of spinal-cord swelling on myelography and CT myelography, initially suggesting the diagnosis of an intramedullary tumor. Spinal-cord swelling was demonstrated more clearly on CT myelography than on conventional myelography. The diagnosis of multiple sclerosis was made with the aid of the CSF findings, the clinical course, and the contracting-cord sign. The ''contracting-cord sign'' means the diminution of the spinal-cord diameter in the chronic stage. Since acute multiple sclerosis may produce spinal-cord swelling simulating a tumor, careful investigations are necessary to avoid unwarranted surgical interventions. (author)

The risk of fracture in incident multiple sclerosis patients

DEFF Research Database (Denmark)

Bazelier, Marloes T; Bentzen, Joan; Vestergaard, Peter

2012-01-01

Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling.......Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling....

Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

Directory of Open Access Journals (Sweden)

Mezei Z

2012-10-01

Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

New and emerging immune-targeted drugs for the treatment of multiple sclerosis.

Science.gov (United States)

Palmer, Alan M

2014-07-01

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.

Effects of Acupuncture on Gait of Patients with Multiple Sclerosis.

Science.gov (United States)

Criado, Maria Begoña; Santos, Maria João; Machado, Jorge; Gonçalves, Arminda Manuela; Greten, Henry Johannes

2017-11-01

Multiple sclerosis is considered a complex and heterogeneous disease. Approximately 85% of patients with multiple sclerosis indicate impaired gait as one of the major limitations in their daily life. Acupuncture studies found a reduction of spasticity and improvement of fatigue and imbalance in patients with multiple sclerosis, but there is a lack of studies regarding gait. We designed a study of acupuncture treatment, according to the Heidelberg model of Traditional Chinese Medicine (TCM), to investigate if acupuncture can be a useful therapeutic strategy in patients with gait impairment in multiple sclerosis of relapsing-remitting type. The sample consisted of 20 individuals with diagnosis of multiple sclerosis of relapsing-remitting type. Gait impairment was evaluated by the 25-foot walk test. The results showed differences in time to walk 25 feet following true acupuncture. In contrast, there was no difference in time to walk 25 feet following sham acupuncture. When using true acupuncture, 95% of cases showed an improvement in 25-foot walk test, compared with 45% when sham acupuncture was done. Our study protocol provides evidence that acupuncture treatment can be an attractive option for patients with multiple sclerosis, with gait impairment.

Natalizumab remains detectable in patients with multiple sclerosis long after treatment is stopped

NARCIS (Netherlands)

Rispens, Theo; Vennegoor, Anke; Wolbink, Gert Jan; Polman, Chris H.; Killestein, Joep

2012-01-01

Natalizumab is frequently used as a treatment for multiple sclerosis (MS). The occurrence of progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients indicates that its prominent beneficial effects need to be balanced against the risks. Also, cessation of the drug seems to be

New management algorithms in multiple sclerosis

DEFF Research Database (Denmark)

Sorensen, Per Soelberg

2014-01-01

complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

Science.gov (United States)

... of this page please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, ... something quite different for a person living with multiple sclerosis, such as his girlfriend's brother, Chuy. The more ...

[Current description of multiple sclerosis].

Science.gov (United States)

Río, Jordi; Montalbán, Xavier

2014-12-01

Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Lung volume recruitment in multiple sclerosis.

Directory of Open Access Journals (Sweden)

Nadim Srour

Full Text Available INTRODUCTION: Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC and cough but the time course of this impairment is unknown. Peak cough flow (PCF is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. OBJECTIVES: Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. METHODS: We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. RESULTS: There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9-190.3 and PCF (192 mL/s/y, 95% 72-311 over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001 and PCF (p = 0.042. CONCLUSION: Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis.

Magnetic resonance in multiple sclerosis

International Nuclear Information System (INIS)

Scotti, G.; Caputo, D.; Cazzullo, C.L.

1986-01-01

Magnetic Resonance Imaging was performed in more than 200 patients with clinical suspicion or knowledge of Multiple Sclerosis. One hundred and forty-seven (60 males and 87 females) had MR evidence of multiple sclerosis lesions. The MR signal of demyelinating plaques characteristically has prolonged T1 and T2 relaxation times and the T2-weighted spin-echo sequences are generally superior to the T1-weighted images because the lesions are better visualized as areas of increased signal intensity. MR is also able to detect plaques in the brainstem, cerebellum and within the cervical spinal cord. MR appears to be an important, non-invasive method for the diagnosis of Multiple Sclerosis and has proven to be diagnostically superior to CT, evoked potentials (EP) and CSF examination. In a selected group of 30 patients, with the whole battery of the relevant MS studies, MR was positive in 100%, CT in 33,3%, EP in 56% and CSF examination in 60%. In patients clinically presenting only with signs of spinal cord involvement or optic neuritis or when the clinical presentation is uncertain MR has proven to be a very useful diagnostic tool for diagnosis of MS by demonstrating unsuspected lesions in the cerebral hemispheres. (orig.)

[Multiple sclerosis, loss of functionality and gender].

Science.gov (United States)

Bravo-González, Félix; Álvarez-Roldán, Arturo

2017-12-01

To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Vision and vision-related outcome measures in multiple sclerosis

Science.gov (United States)

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

[Effects of nutritional status on the multiple sclerosis disease: systematic review].

Science.gov (United States)

Ródenas Esteve, Irene; Wanden-Berghe, Carmina; Sanz-Valero, Javier

2018-01-19

To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.

Characteristics and correlates of coping with multiple sclerosis: a systematic review.

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Keramat Kar, Maryam; Whitehead, Lisa; Smith, Catherine M

2017-10-10

The purpose of this systematic review was to examine coping strategies that people with multiple sclerosis use, and to identify factors that influence their coping pattern. This systematic review followed the Joanna Briggs Institute guidelines for synthesizing descriptive quantitative research. The following databases were searched from the inception of databases until December 2016: Ovid (Medline, Embase, CINAHL, and PsycINFO), Science Direct, Web of Science, and Scopus. Manual search was also conducted from the reference lists of retrieved articles. Findings related to the patterns of coping with multiple sclerosis and factors influencing coping with multiple sclerosis were extracted and synthesized. The search of the database yielded 455 articles. After excluding duplicates (n = 341) and studies that did not meet the inclusion criteria (n = 27), 71 studies were included in the full-text review. Following the full-text, a further 21 studies were excluded. Quality appraisal of 50 studies was completed, and 38 studies were included in the review. Synthesis of findings indicated that people with multiple sclerosis use emotional and avoidance coping strategies more than other types of coping, particularly in the early stages of the disease. In comparison to the general population, people with multiple sclerosis were less likely to use active coping strategies and used more avoidance and emotional coping strategies. The pattern of coping with multiple sclerosis was associated with individual, clinical and psychological factors including gender, educational level, clinical course, mood and mental status, attitude, personality traits, and religious beliefs. The findings of this review suggest that considering individual or disease-related factors could help healthcare professionals in identifying those less likely to adapt to multiple sclerosis. This information could also be used to provide client-centered rehabilitation for people living with multiple

Chronic progressive multiple sclerosis

International Nuclear Information System (INIS)

Buffoli, A.; Micheletti, E.; Capra, R.; Mattioli, F.; Marciano', N.

1991-01-01

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

Science.gov (United States)

Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

2015-08-15

Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica. Copyright © 2015 Elsevier B.V. All rights reserved.

MR spectroscopy of cervical spinal cord in patients with multiple sclerosis

International Nuclear Information System (INIS)

Kendi, Ayse Tuba Karaguelle; Kendi, Mustafa; Tan, Funda Uysal; Tellioglu, Serdar; Huvaj, Sinef

2004-01-01

MR spectroscopy (MRS) of the brain in patients with multiple sclerosis has been well studied. However, in vivo MRS of the spinal cord in patients with MR spectroscopy has not been reported to our knowledge. We performed MRS of normal-appearing cervical spinal cords in multiple sclerosis patients and in healthy controls. N-acetyl aspartate was shown to be reduced within the cervical spinal cord of multiple sclerosis patients when compared with healthy controls. This finding supports axonal loss and damage within even normal-appearing spinal cords of multiple sclerosis patients. (orig.)

Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

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Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

2017-07-01

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Increasing occurrence of multiple sclerosis in women correlates to hygiene level

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Wojciech Cendrowski

2014-12-01

Full Text Available Introduction: The increasing incidence of multiple sclerosis, particularly among women in Europe and North America, has a multifactorial aetiology. Method: The aim of the current study was to ascertain the relation between the hygiene level and occurrence of multiple sclerosis in women in Poland. The study was based on a large cohort of 14,200 multiple sclerosis individuals (male – 6,106, female – 8,094 who died in the years 1981–2010 in Poland. The female to male ratio (the F:M ratio in the multiple sclerosis group was calculated using the number of deaths per year. The rate of late mortality in infants (LMI per 1,000 live births yearly was used as a marker of the hygiene level. A correlation analysis was carried out between the rate of LMI and the F:M ratio in the multiple sclerosis cohort in the years 1981–2010. Demographic data were obtained from the Central Statistical Office in Warsaw. Results: The F:M ratio in the multiple sclerosis group evidently increased (range 1.08–1.79 in the years 1981–2010, showing increasing occurrence of multiple sclerosis in women (p < 0.0001. A significant, strong and inverse correlation was found between the marker of the hygiene level (LMI rate and the F:M ratio in the multiple sclerosis group over three decades: linear correlation coefficient by Pearson: r = –0.693, p < 0.0001. By contrast with this result, no correlation was established between the hygiene level marker and proportion of women to men in the general population on account of extremely low variance of the F:M ratio (0.000025. Conclusion: The improvement of the hygiene level showed association with the increasing occurrence of multiple sclerosis in women in the years 1981–2010. The higher the hygiene level was, the greater the occurrence of female multiple sclerosis in Poland.

Treatment of multiple sclerosis with chinese scalp acupuncture.

Science.gov (United States)

Hao, Jason Jishun; Cheng, Wei; Liu, Ming; Li, He; Lü, Xiaolin; Sun, Zhongren

2013-01-01

Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission.

Acute form of multiple sclerosis in a child simulation encephalitis

International Nuclear Information System (INIS)

Niagolova, S.; Karapasheva, V.; Nikolova, M.

2007-01-01

Multiple sclerosis (MS) is considered the most common demyelinating process involving the CNS. Although usually considered an adult disease multiple sclerosis can begin to manifest during childhood. The clinical presentation of the disease in early childhood can range from paraesthesias to dramatic presentations, suggesting diffuse encephalopathy with cerebral oedema, meningismus and impaired consciousness. Multiple sclerosis is usually characterized by a typical relapsing-remitting clinical course. But there are acute, clinically fulminant forms with atypical. neurologic symptoms and death in months. MRI has become increasingly relevant in the diagnosis of multiple sclerosis in the past years. Yet, the specificity is limited. Atypical forms of MS and other diseases of CNS may show similar patterns on MRI. We report a case of 7 years old boy with clinically fulminant Marburg type of multiple sclerosis that ended with death in two months. The patient was a diagnostic problem despite the certain degree of clinical and radiological suspicion. The postmortem diagnosis is based on pathomorphologic changes (gross pathologic and microscopic features) in CNS.The present case is of clinical, radiological and pathomorphologic interest because of its early onset in childhood, unusual clinical course and acute progression. Awareness of the MRI features of multiple sclerosis and MS-variants (subtypes) may help in such atypical presentations in childhood. (authors)

Treatment of acute relapses in multiple sclerosis at home with oral dexamethasone : a pilot study

NARCIS (Netherlands)

De Keyser, J; Zwanikken, C; Zorgdrager, A; Oenema, D

The objective of this study was to investigate the feasibility of treating relapses of multiple sclerosis (MS) at home with oral dexamethasone. Twenty-five out of 28 consecutive patients with MS who presented with a relapse of less than 2 weeks' duration were treated on an open basis with oral

Amyloid PET in pseudotumoral multiple sclerosis.

Science.gov (United States)

Matías-Guiu, Jordi A; Cabrera-Martín, María Nieves; Cortés-Martínez, Ana; Pytel, Vanesa; Moreno-Ramos, Teresa; Oreja-Guevara, Celia; Carreras, José Luis; Matías-Guiu, Jorge

2017-07-01

Pseudotumoral multiple sclerosis is a rare form of demyelinating disease of the central nervous system. Positron emission tomography (PET) using amyloid-tracers has also been suggested as a marker of damage in white matter lesions in multiple sclerosis due to the nonspecific uptake of these tracers in white matter. We present the case of a 59 year-old woman with a pathological-confirmed pseudotumoral multiple sclerosis, who was studied with the amyloid tracer 18 F-florbetaben. The patient had developed word-finding difficulties and right hemianopia twelve years ago. In that time, MRI showed a lesion on the left hemisphere with an infiltrating aspect in frontotemporal lobes. Brain biopsy showed demyelinating areas and inflammation. During the following years, two new clinical relapses occurred. 18 F-florbetaben PET showed lower uptake in the white matter lesion visualized in the CT and MRI images. Decreased tracer uptake was also observed in a larger area of the left hemisphere beyond the lesions observed on MRI or CT. White matter lesion volume on FLAIR was 44.2mL, and tracer uptake change between damaged white matter and normal appearing white matter was - 40.5%. Standardized uptake value was inferior in the pseudotumoral lesion than in the other white matter lesions. We report the findings of amyloid PET in a patient with pseudotumoral multiple sclerosis. This case provides further evidence on the role of amyloid PET in the assessment of white matter and demyelinating diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased Concentrations of Interleukin-33 in the Serum and Cerebrospinal Fluid of Patients with Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Abdollah Jafarzadeh

2016-01-01

Full Text Available Objectives: Interleukin (IL-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid (CSF IL-33 concentrations in patients with multiple sclerosis (MS. Methods: Blood specimens were obtained from 140 patients with MS (46 males and 94 females with various disease patterns and treatment plans and 140 healthy subjects (47 males and 93 females, who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and age-matched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay. Results: The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group (p<0.001 and p<0.050, respectively. The serum IL-33 concentrations were also significantly higher in newly diagnosed (untreated patients and patients treated with methylprednisolone or with interferon-β and methylprednisolone compared to the healthy patient group (p<0.007, p<0.002, and p<0.010, respectively. Moreover, the serum IL-33 concentrations in patients with relapsing-remitting (RRMS, primary progressive (PPMS, and secondary progressive (SPMS forms of the disease were significantly higher than in the healthy control group (p<0.006, p<0.001, and p<0.020, respectively. Conclusions: Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-β plus methylprednisolone has no influence on IL-33 concentrations.

Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study.

Science.gov (United States)

Bertoglio, J C; Baumgartner, M; Palma, R; Ciampi, E; Carcamo, C; Cáceres, D D; Acosta-Jamett, G; Hancke, J L; Burgos, R A

2016-05-23

Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.

Current concepts in multiple sclerosis

International Nuclear Information System (INIS)

Wiethoelter, Horst; Dichgans, Johannes

1991-01-01

This volume contains 9 articles dealing with the use of nuclear magnetic resonance imaging and positron emitted tomography in the diagnosis and staging of multiple sclerosis. (H.W.). refs.; figs.; tabs

Epidemiological and biochemical aspects of progression in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus Werner

2008-01-01

Patients with a progressive form of multiple sclerosis have the worst prognosis. They can expect that their symptoms will steadily worsen, and there is currently no treatment that has a proven effect on progressive multiple sclerosis. The underlying pathophysiology of the progressive forms of

Seizures in multiple sclerosis

NARCIS (Netherlands)

Koch, Marcus; Uyttenboogaart, Maarten; Polman, Susan; De Keyser, Jacques

Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

2017-01-01

on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

Suicide and multiple sclerosis

DEFF Research Database (Denmark)

Stenager, E N; Stenager, Egon; Koch-Henriksen, N

1992-01-01

In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...... with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age......, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males...

Multiple sclerosis: general features and pharmacologic approach

International Nuclear Information System (INIS)

Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

2009-01-01

Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

Daclizumab for the treatment of relapsing-remitting multiple sclerosis.

Science.gov (United States)

Herwerth, Marina; Hemmer, Bernhard

2017-06-01

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system. Over the last two decades, the number of therapeutic options for the treatment of relapsing remitting MS (RRMS) has been constantly growing, providing new treatment options to patients. Areas covered: Herein, the authors review the recently approved monoclonal antibody daclizumab for the treatment of RRMS. Based on original articles, they discuss its mode of action and evaluate its efficacy and safety profile compared to other available agents. Expert opinion: The IL-2 receptor modulator daclizumab is a new highly effective agent for the treatment of RRMS with novel immunomodulatory properties. Compared to interferon-beta i.m., daclizumab is more effective in reducing relapse rates and MRI activity. However, its use is limited by the risk of autoimmune disorders and hepatotoxicity. Similar to other monoclonal antibodies for RRMS, therapy with daclizumab needs a strict preselection and monitoring of patients based on individual risk benefit assessment. Given its substantial effectiveness, daclizumab can be an attractive option for patients with highly active MS.

What's new in multiple sclerosis spasticity research? Poster session highlights.

Science.gov (United States)

Linker, Ralf

2017-11-01

Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

Multiple sclerosis and herpesvirus interaction

Directory of Open Access Journals (Sweden)

Guilherme Sciascia do Olival

2013-09-01

Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

Orbital phlebography for differentiation between multiple sclerosis and venous vasculitis in subacute blindness

International Nuclear Information System (INIS)

Hannerz, J.; Ericson, K.; Bergstrand, G.

1988-01-01

Thirteen consecutive patients with subacute unilateral loss of vision and periorbital pain but without pathology of the fundus or increased erythrocyte sedimentation rate, were investigated with visual evoked response, electrophoresis of serum and cerebrospinal fluid, and orbital phlebography. Seven of these patients were found to suffer from multiple sclerosis. The remaining 6 were considered to have venous vasculitis. There was a spontaneous recovery from visual impairment in all patients with multiple sclerosis, but not in patients with venous vasculitis. Of the latter patients, only two, who were treated with steroids within the first four days after onset of symptoms, regained vision. It appears that orbital phlebography is the diagnostic procedure of choice for proper management of patients with subacute loss of vision. (orig.)

Multiple sclerosis in magnetic resonance

International Nuclear Information System (INIS)

Bekiesinska-Figatowska, M.; Walecki, J.; Stelmasiak, Z.

1994-01-01

The authors analyzed MR examination of 277 patients with multiple sclerosis. White matter hyperintesities in brain were found in 270 of them, in spinal cord in 32. The most frequently they were found in periventricular white matter, in subcortical localization and in the corpus callosum. MR examination allows the estimate the activity of the disease on the basis of the presence of edema around the plaques and their contrast enhancement with Gd-DTPA. About one third of all cases were accompanied by cortical brain atrophy (the most often seen in the frontal lobes), subcortical brain atrophy was less frequent. In about two third of all cases the corpus callosum atrophy was found. MR examination is a highly sensitive method of multiple sclerosis diagnosis, of the assessment of its activity and progression. (author)

Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm.

Science.gov (United States)

Giovannoni, Gavin

2018-06-01

The treatment of multiple sclerosis is evolving rapidly with 11 classes of disease-modifying therapies (DMTs). This article provides an overview of a new classification system for DMTs and treatment paradigm for using these DMTs effectively and safely. A summary of research into the use of more active approaches to early and effective treatment of multiple sclerosis with defined treatment targets of no evident disease activity (NEDA). New insights are discussed that is allowing the field to begin to tackle more advanced multiple sclerosis, including people with multiple sclerosis using wheelchairs. However, the need to modify expectations of what can be achieved in more advanced multiple sclerosis are discussed; in particular, the focus on neuronal systems with reserve capacity, for example, upper limb, bulbar and visual function. The review describes a new more active way of managing multiple sclerosis and concludes with a call to action in solving the problem of slow adoption of innovations and the global problem of untreated, or undertreated, multiple sclerosis.

ECTRIMS/ACTRIMS 2017: Closing in on neurorepair in progressive multiple sclerosis.

Science.gov (United States)

Kremer, David; Küry, Patrick; Hartung, Hans-Peter

2018-04-01

While there is now a multitude of potent medications for relapsing-remitting multiple sclerosis (RRMS), effective therapies targeting neurodegeneration in progressive multiple sclerosis types are still lacking. Stimulation of neurorepair in this disease remains a pathogenetically defined treatment goal. However, therapeutic progress is slowed by the still inadequate tool set to capture "regeneration/repair" in MS and to define appropriate outcomes in clinical trials. In this review, we discuss studies investigating promising regenerative agents for progressive MS which were recently presented during the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)/Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017 meeting in Paris.

Mining gene expression data of multiple sclerosis.

Directory of Open Access Journals (Sweden)

Pi Guo

Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

Vaccines and multiple sclerosis

DEFF Research Database (Denmark)

Frederiksen, J. L.; Topsøe Mailand, M.

2017-01-01

An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live...

Alemtuzumab for the treatment of multiple sclerosis

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Willis MD

2015-03-01

Full Text Available Mark D Willis, Neil P Robertson Institute of Psychological Medicine and Clinical Neuroscience, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK Abstract: Alemtuzumab is an anti-CD52 monoclonal antibody, recently approved for the treatment of active, relapsing multiple sclerosis (MS. Administration of alemtuzumab causes a rapid and dramatic reduction in circulating lymphocytes, with a predictable subsequent pattern of immune reconstitution. Although the precise mode of action remains unclear, treatment results in a marked reduction in annualized relapse rates, slowing of disability progression compared with an active comparator, and may even cause disability reversal. Although conferring clear clinical benefits, alemtuzumab carries a significant long-term risk of autoimmune disease (AID, which has a particular predilection for the thyroid gland, although a wide range of other disorders have also been reported. However, risks of AID can usually be anticipated and treated successfully, provided rigorous monitoring and surveillance protocols are followed by clinicians and patients alike. Despite its immunosuppressive mechanism of action serious infections are rare and malignancies commonly associated with immunodeficiency have not been observed to date. Alemtuzumab’s unique mode of administration, as well as it’s durability of effect, provides an important addition to currently available therapeutic interventions for MS, and in particular is a valuable treatment option in recent onset and highly active relapsing disease. Keywords: multiple sclerosis, alemtuzumab, autoimmune disease

Multiple Sclerosis: Hope Through Research | NIH MedlinePlus the Magazine

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... of this page please turn Javascript on. Feature: Multiple Sclerosis Hope Through Research Past Issues / Spring 2012 Table ... that television journalist Neil Cavuto was diagnosed with multiple sclerosis (MS) more than 15 years ago. And that ...

Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review.

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Suneetha, A; Raja Rajeswari, K

2016-04-15

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS affecting both white and grey matter. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2). Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapy with dimethyl fumarate. The clinical utility of DMF in multiple sclerosis is being explored through phase III trials with BG-12, which is an oral therapeutic agent. Currently a wide research is going on to find out the exact mechanism of DMF, till date it is not clear. Based on strong signals of nephrotoxicity in non-humans and the theoretical risk of renal cell cancer from intracellular accumulation of fumarate, post-marketing study of a large population of patients will be necessary to fully assess the long-term safety of dimethyl fumarate. The current treatment goals are to shorten the duration and severity of relapses, prolong the time between relapses, and delay progression of disability. In this regard, dimethyl fumarate offers a promising alternative to orally administered fingolimod (GILENYA) or teriflunomide (AUBAGIO), which are currently marketed in the United States under FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) programs because of serious safety concerns. More clinical experience with all three agents will be necessary to differentiate the tolerability of long-term therapy for patients diagnosed with multiple sclerosis. This write-up provides the detailed information of dimethyl fumarate in treating the neuro disease, multiple sclerosis and its mechanism involved via

Survey of diagnostic and treatment practices for multiple sclerosis in Europe.

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Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Gionvannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G

2017-03-01

Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe. © 2017 EAN.

The essential role of t cells in multiple sclerosis: A reappraisal

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Cris S Constantinescu

2014-04-01

Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

International Nuclear Information System (INIS)

Biggins, J.A.; Taylor, A.; Caspary, E.A.

1978-01-01

Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

Reproductive History and Risk of Multiple Sclerosis

DEFF Research Database (Denmark)

Nielsen, N. M.; Jorgensen, K. T.; Stenager, E.

2011-01-01

Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million...... Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis...

EVALUATION OF IMMUNOTOXICITY OF THE THERAPEUTIC DRUG PROLONGED ACTION FOR MULTIPLE SCLEROSIS ON RHESUS MONKEYS

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A. B. Dzheliya

2015-01-01

Full Text Available This article presents the results of immunotoxicity study of a novel slow-release drug for multiple sclerosis treatment based on recombinant human interferon beta-1а. The test article is polyethylene glycol (PEG-conjugated interferon beta-1a. Performed modification allows to improve pharmacokinetic parameters, decrease immunogenicity and elevate tolerance that significantly increases safety of the test article. The study is performed in nonhuman primates – rhesus monkeys (Macaca mulatta. The species, used in this study, is susceptible to human interferon beta-1a that has previously been shown in specific activity studies. Dynamics of peripheral blood lymphocyte subsets composition, activated lymphocyte count (based on the presence of early activation marker, serum antibodies (IgM, IgG, IgA and IgE level and ratio were assessed within in vivo experiments. The effect of interferon beta-1a on CD69 expression was examined in mononuclear cells culture. It was shown that the test article causes changes in lymphocyte subsets ratio (decrease of NK-cells relative count with T-lymphocytes relative count elevation in primates’ peripheral blood. Revealed changes were reversible and dose-independent. It was not shown that the test article have reliable effect on CD69 expression rate. There was no evidence of test article effect on level and ratio of serum antibodies and polymorphonucleocytes phagocytic rate in the absence of additional antigenic exposure. The results obtained during the experiment indicate the absence of pathological effect of the test article on the nonhuman primates’ immune system.

Defining active progressive multiple sclerosis

DEFF Research Database (Denmark)

Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

2017-01-01

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

Cognitive deficits in multiple sclerosis

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Lund, H; Jønsson, A; Andresen, Jesper Graubæk

2012-01-01

of the cognitive impairment seen in MS and constitute a supplement to traditional measurement of T2 lesion volume. Materials and Methods - Fifty patients with clinically definite MS were included (38 women, 12 men). Patients were MR scanned, neuropsychologically tested, and evaluated clinically with the Kurtzke......Objectives - Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part...... Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. Results - We found distinct...

Synaptic pathology in the cerebellar dentate nucleus in chronic multiple sclerosis.

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Albert, Monika; Barrantes-Freer, Alonso; Lohrberg, Melanie; Antel, Jack P; Prineas, John W; Palkovits, Miklós; Wolff, Joachim R; Brück, Wolfgang; Stadelmann, Christine

2017-11-01

In multiple sclerosis, cerebellar symptoms are associated with clinical impairment and an increased likelihood of progressive course. Cortical atrophy and synaptic dysfunction play a prominent role in cerebellar pathology and although the dentate nucleus is a predilection site for lesion development, structural synaptic changes in this region remain largely unexplored. Moreover, the mechanisms leading to synaptic dysfunction have not yet been investigated at an ultrastructural level in multiple sclerosis. Here, we report on synaptic changes of dentate nuclei in post-mortem cerebella of 16 multiple sclerosis patients and eight controls at the histological level as well as an electron microscopy evaluation of afferent synapses of the cerebellar dentate and pontine nuclei of one multiple sclerosis patient and one control. We found a significant reduction of afferent dentate synapses in multiple sclerosis, irrespective of the presence of demyelination, and a close relationship between glial processes and dentate synapses. Ultrastructurally, we show autophagosomes containing degradation products of synaptic vesicles within dendrites, residual bodies within intact-appearing axons and free postsynaptic densities opposed to astrocytic appendages. Our study demonstrates loss of dentate afferent synapses and provides, for the first time, ultrastructural evidence pointing towards neuron-autonomous and neuroglia-mediated mechanisms of synaptic degradation in chronic multiple sclerosis. © 2016 International Society of Neuropathology.

Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator.

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Boggild, Mike; Palace, Jackie; Barton, Pelham; Ben-Shlomo, Yoav; Bregenzer, Thomas; Dobson, Charles; Gray, Richard

2009-12-02

To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis. Prospective cohort study with historical comparator. Specialist multiple sclerosis clinics in 70 centres in the United Kingdom. Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme. Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists. Observed utility weighted progression in disability at two years' follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials. In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset ("deviation score" of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from -72% (using raw baseline disability status scale scores, rather than applying a "no improvement" algorithm) to 156% (imputing missing data for year two from progression rates for year one). It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the "no improvement" rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.

Abundance of Stress, Anxiety and Depression in Multiple Sclerosis Patients

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A. Dehghan

2013-05-01

Conclusion: The findings of this research revealed high stress, anxiety and depression in Multiple Sclerosis Patients that can jeopardize their health. Hence the providing appropriate education for coping and adapting with the symptoms in Multiple Sclerosis Patients seems to be necessary.

Multiple sclerosis and other white matter diseases

International Nuclear Information System (INIS)

Zimmerman, R.A.

1991-01-01

The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)

Zinc in multiple sclerosis

DEFF Research Database (Denmark)

Bredholt, Mikkel; Fredriksen, Jette Lautrup

2016-01-01

In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS...

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

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2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Magnetic resonance imaging in the diagnostics of multiple sclerosis

International Nuclear Information System (INIS)

Larsen, J.P.; Tjoerstad, K.; Kaass, B.; Oedegaard, H.

1987-01-01

Multiple sclerosis is an important and frequent neurological disease and the diagnosis might be difficult. The clinical criteria of multiple sclerosis and the role of laboratory examinations in the diagnosis of the disease are discussed. In particular the help offered by the magnetic resonance imaging method is the subject of this paper. Three patients are reported and discussed

Clustering of multiple sclerosis in Galion, Ohio, 1982-1985

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Ingalls, T.H. (Boston Univ. School of Medicine, MA (USA))

1989-09-01

Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

Neuromyelitis optica and multiple sclerosis

DEFF Research Database (Denmark)

Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.

2015-01-01

Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel...

Uric acid in multiple sclerosis

NARCIS (Netherlands)

Koch, M; De Keyser, J

Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic

Occupational therapy for multiple sclerosis.

NARCIS (Netherlands)

Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Cardol, M.; Nes, J.C.M. van de; Ende, C.H.M. van den

2003-01-01

Background: Multiple sclerosis (MS) patients are referred to occupational therapy with complaints about fatigue, limb weakness, alteration of upper extremity fine motor coordination, loss of sensation and spasticity that causes limitations in performance of activities of daily living and social

CHANGES IN TUMOR NECROSIS FACTOR ALFA DURING TREATMENT OF PATIENTS WITH MULTIPLE SCLEROSIS BY TRANSIMMUNIZATION METHOD

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A. V. Kil'dyushevskiy

2016-01-01

Full Text Available Background: Despite the availability of a  large number of treatments for multiple sclerosis with various targets, these treatments are not always effective. According to the literature, experimental studies have shown a  significant decrease in tumor necrosis factor alfa (TNF-α with the use of extracorporeal photochemotherapy. Aim: To assess changes in TNF-α in patients with multiple sclerosis during treatment with transimmunization. Materials and methods: The study recruited 13 adult patients with multiple sclerosis. Serum TNF-α was measured by immunochemiluminescence analysis (IMMULITE 1000, Siemens. The patients were treated by transimmunization, i.e. a  modified photopheresis. Two hours before the procedure, Ammifurin (8-methoxypsoralene was administered to all the patients, then their mononuclear cells were isolated under PBSC protocol with Haemonetics MCS+ cell separator. Thereafter, mononuclear cells were irradiated with ultraviolet for 90  minutes and incubated for 20 hours at 37 °С. The next day the cells were re-infused to the patients. The procedure was performed 2  times per week for 6  months, then once per 4  months. Results: Before transimmunization, mean TNF-α level in adult patients with multiple sclerosis was 9.958±0.812  pg/mL (normal, below 8.1 pg/mL. After transimmunization, its level was 6.992±0.367  pg/mL (р<0.05. Conclusion: Ultraviolet irradiation of peripheral blood monocytes with their subsequent incubation (transimmunization led to a 30% decrease of serum TNF-α in patients with multiple sclerosis. This indicates a suppressive effect of transimmunization on TNF-α. Hence, in patients with multiple sclerosis transimmunization exerts an anti-inflammatory effect.

The management of multiple sclerosis in children: a European view

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Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey

2010-01-01

About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity i...

Pediatric multiple sclerosis: current perspectives on health behaviors

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Sikes EM

2018-03-01

Full Text Available Elizabeth Morghen Sikes,1 Robert W Motl,1 Jayne M Ness2 1Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Pediatric Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Purpose: Pediatric-onset multiple sclerosis (POMS accounts for ~5% of all multiple sclerosis cases, and has a prevalence of ~10,000 children in the USA. POMS is associated with a higher relapse rate, and results in irreversible disability on average 10 years earlier than adult-onset multiple sclerosis. Other manifestations of POMS include mental and physical fatigue, cognitive impairment, and depression. We believe that the health behaviors of physical activity, diet, and sleep may have potential benefits in POMS, and present a scoping review of the existing literature. Methods: We identified papers by searching three electronic databases (PubMed, GoogleScholar, and CINAHL. Search terms included: pediatric multiple sclerosis OR pediatric onset multiple sclerosis OR POMS AND health behavior OR physical activity OR sleep OR diet OR nutrition OR obesity. Papers were included in this review if they were published in English, referenced nutrition, diet, obesity, sleep, exercise, or physical activity, and included pediatric-onset multiple sclerosis as a primary population. Results: Twenty papers were identified via the literature search that addressed health-promoting behaviors in POMS, and 11, 8, and 3 papers focused on diet, activity, and sleep, respectively. Health-promoting behaviors were associated with markers of disease burden in POMS. Physical activity participation was associated with reduced relapse rate, disease burden, and sleep/rest fatigue symptoms. Nutritional factors, particularly vitamin D intake, may be associated with relapse rate. Obesity has been associated with increased risk of developing POMS. POMS is associated with better sleep hygiene, and this may benefit fatigue and quality of life

Resveratrol Neuroprotection in a Chronic Mouse Model of Multiple Sclerosis

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Zoe eFonseca-Kelly

2012-05-01

Full Text Available Resveratrol is a naturally-occurring polyphenol that activates SIRT1, an NAD-dependent deacetylase. SRT501, a pharmaceutical formulation of resveratrol with enhanced systemic absorption, prevents neuronal loss without suppressing inflammation in mice with relapsing experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis. In contrast, resveratrol has been reported to suppress inflammation in chronic EAE, although neuroprotective effects were not evaluated. The current studies examine potential neuroprotective and immunomodulatory effects of resveratrol in chronic EAE induced by immunization with myelin oligodendroglial glycoprotein peptide in C57/Bl6 mice. Effects of two distinct formulations of resveratrol administered daily orally were compared. Resveratrol delayed the onset of EAE compared to vehicle-treated EAE mice, but did not prevent or alter the phenotype of inflammation in spinal cords or optic nerves. Significant neuroprotective effects were observed, with higher numbers of retinal ganglion cells found in eyes of resveratrol-treated EAE mice with optic nerve inflammation. Results demonstrate that resveratrol prevents neuronal loss in this chronic demyelinating disease model, similar to its effects in relapsing EAE. Differences in immunosuppression compared with prior studies suggest that immunomodulatory effects may be limited and may depend on specific immunization parameters or timing of treatment. Importantly, neuroprotective effects can occur without immunosuppression, suggesting a potential additive benefit of resveratrol in combination with anti-inflammatory therapies for multiple sclerosis.

Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

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Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

2015-01-01

The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

Fingolimod hydrochloride for the treatment of relapsing remitting multiple sclerosis.

Science.gov (United States)

Thomas, Katja; Proschmann, Undine; Ziemssen, Tjalf

2017-10-01

Fingolimod was the first oral and the first in class disease modifying treatment in multiple sclerosis that acts as sphingosine-1-phospathe receptor agonist. Since approval in 2010 there is a growing experience with fingolimod use in clinical practice, but also next-generation sphingosin-1-receptor agonists in ongoing clinical trials. Growing evidence demonstrates additional effects beyond impact on lymphocyte circulation, highlighting further promising targets in multiple sclerosis therapy. Areas covered: Here we present a systematic review using PubMed database searching and expert opinion on fingolimod use in clinical practice. Long-term data of initial clinical trials and post-marketing evaluations including long-term efficacy, safety, tolerability and management especially within growing disease modifying treatment options and pre-treatment constellation in multiple sclerosis patients are critically discussed. Furthermore novel findings in mechanism of actions and prospective on additional use in progressive forms in multiple sclerosis are presented. Expert opinion: There is an extensive long-term experience on fingolimod use in clinical practice demonstrating the favorable benefit-risk of this drug. Using a defined risk management approach experienced MS clinicians should apply fingolimod after critical choice of patients and review of clinical aspects. Further studies are essential to discuss additional benefit in progressive forms in multiple sclerosis.

Self care programs and multiple sclerosis: physical therapeutics treatment - literature review.

Science.gov (United States)

Demaille-Wlodyka, S; Donze, C; Givron, P; Gallien, P

2011-03-01

To clarify the therapeutic education program impact with multiple sclerosis patients, literature review. Highlight contents and efficacy. A non-systematic review on Medline, PubMed and Cochrane library databases from 1966 to 2010 using the following keywords: "multiple sclerosis", "self-care", "self-management" and specific symptoms keywords. Clinical trials and randomized clinical trials, as well as literature reviews published in English, French and German will be analyzed. Counseling is a part of the non-pharmacological management of chronic illnesses such as multiple sclerosis. Symptoms' diversity and the different clinical forms limit standardized programs of self-care management, applicable to patients. In the literature review, counseling programs have often low metrology. A behavior change with patients and medical staff could exist. To empower the patient, to reduce symptoms' impact and to improve treatment access are the aims of educational therapy. Therapeutic education program for multiple sclerosis patients could progress with their standardization and assessment, for each sign. To promote the educational therapy of multiple sclerosis patients, a specific training for medical staff, as specific financing are necessary. 2011 Elsevier Masson SAS. All rights reserved.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

Science.gov (United States)

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

How multiple sclerosis is related to animal illness, stress and diabetes

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Warren, S.A.; Warren, K.G.; Greenhill, S.; Paterson, M.

1982-02-15

At the University of Alberta's multiple sclerosis research clinic 100 patients with multiple sclerosis were matched to control patients for age, sex, race and zone of residence before the age of 15 years. Case and control subjects were interviewed and information was collected by questionnaire on factors that might play a role in the development of multiple sclerosis. The only factors found to be significantly associated with the development of this disorder were a history of leisure time spent in physical activities before the onset of symptoms, exposure to animal illness -- specifically canine distemper -- and a history of severe or prolonged emotional stress. The study also confirmed a familial predisposition to multiple sclerosis and suggested a relation between the disorder and a personal or family history of diabetes mellitus.

The immunogenetics of multiple sclerosis

DEFF Research Database (Denmark)

Svejgaard, A.

2008-01-01

with complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...

Vascular aspects of multiple sclerosis

NARCIS (Netherlands)

D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques

Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial

Effect of natalizumab treatment on circulating plasmacytoid dendritic cells: a cross-sectional observational study in patients with multiple sclerosis.

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Pia Kivisäkk

Full Text Available Dendritic cells (DCs serve a critical role both in promoting and inhibiting adaptive immunity. The goal of this study was to investigate the effect of natalizumab (NTZ treatment on DC numbers, phenotype, and function in patients with multiple sclerosis (MS.Frequency and phenotype of myeloid and plasmacytoid DCs (MDCs and PDCs, respectively were analyzed in blood from two separate cohorts of untreated, interferon-treated, or NTZ-treated MS patients. In addition, PDCs were stimulated with CpG-containing oligonucleotides or co-cultured with homologous T cells in the presence or absence of NTZ in vitro to determine functional effects of NTZ treatment.We observed that NTZ treatment was associated with a 25-50% reduction in PDC frequency in peripheral blood as compared to untreated MS patients, while the frequency of MDCs was unchanged. PDCs in NTZ-treated patients displayed a mature, activated phenotype with increased expression of HLA-DR, TLR9, CCR7, IL-6 and IL-12. In contrast, in vitro treatment with NTZ did not increase markers of PDC activation or their ability to induce T cell differentiation.Our study shows that NTZ treatment is associated with a reduced frequency of PDCs in the peripheral circulation, but that PDCs in NTZ-treated individuals display an activated phenotype. Taken together the data suggests that transmigration of activated PDCs is preferentially affected by blockade of integrin α4 leading to an increased frequency of activated PDCs in blood.

The enigma of multiple sclerosis: inflammation and neurodegeneration cause heterogeneous dysfunction and damage

DEFF Research Database (Denmark)

Owens, Trevor

2003-01-01

progression correlate with axonal damage, and that brain atrophy resulting from axonal loss is a feature of early multiple sclerosis, and is not restricted to the secondary progressive forms of the disease. Inflammatory mediators (CD8 T cells and antibodies) are implicated in axonal damage, and treatment...... cells for oligodendrocytes. SUMMARY: Oligodendrocyte precursors are abundant in multiple sclerosis lesions, but fail to remyelinate. Oligodendrocyte growth and regeneration are probably compromised by the action of growth inhibitory signals and lack of growth stimuli. Inflammatory cells and mediators......PURPOSE OF REVIEW: The demyelinating disease multiple sclerosis has an autoimmune inflammatory component, which has dominated the description of multiple sclerosis. A degenerative component to multiple sclerosis was always apparent, but was underappreciated until recently. Recent work has brought...

Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.

Science.gov (United States)

Kremenchutzky, Marcelo; O'Connor, Paul; Hohlfeld, Reinhard; Zhang-Auberson, Lixin; von Rosenstiel, Philipp; Meng, Xiangyi; Grinspan, Augusto; Hashmonay, Ron; Kappos, Ludwig

2014-05-01

Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis. This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history. Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration. Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo). Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Corrigendum to ‘Multiple sclerosis: New insights and trends’

Directory of Open Access Journals (Sweden)

Khaled Mohamed Mohamed Koriem

2017-05-01

Full Text Available Multiple sclerosis (MS is the most famous autoimmune disease attacking the central nervous system. It attacks people from age 20–50 years old and the females' attacks double than males' attacks. MS is an autoimmune disease affecting principally the central nervous system that causes nerve sheath demyelination, followed by axon damage and paralysis. MS symptoms include muscle weakness, weak reflexes, muscle spasm, difficulties in movement and unbalance. Many factors may be responsible for MS: microorganism, virus, smoking, stress, environmental toxins, contaminated diet and gout. MS is widely spread in the population in North Europe and this is related to lack of vitamin D due to decrease of sunlight exposure. MS biomarkers include nitric oxide, interleukin-6, nitric oxide synthase, fetuin-A and osteopontin. MS is not a genetic disease (not transferred from parents into next generations but MS appears when leukocyte antigen system-related genes are changed in human chromosome 6. The physiology of MS patients is controlled by numbers of biological processes such as activation of immune-inflammatory, oxidative and nitrosative stress pathways. MS includes two main steps: (1 myelin sheath destruction and formation of lesions and, (2 inflammation. Four types of MS can be distinguished: relapsing-remitting, primary progressive, secondary progressive and progressive relapsing. Nine treatments have been accepted for relapsing-remitting MS type: interferon β-1a, interferon β-1b, mitoxantrone, natalizumab, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. However, the only treatment used is mitoxantrone for progressive MS with many side effects. Complementary treatments are also used in MS treatments such as vitamin D, Yoga, medicinal plants, oxygen therapy, acupuncture and reflexology.

Axonal loss in the multiple sclerosis spinal cord revisited.

Science.gov (United States)

Petrova, Natalia; Carassiti, Daniele; Altmann, Daniel R; Baker, David; Schmierer, Klaus

2018-05-01

Preventing chronic disease deterioration is an unmet need in people with multiple sclerosis, where axonal loss is considered a key substrate of disability. Clinically, chronic multiple sclerosis often presents as progressive myelopathy. Spinal cord cross-sectional area (CSA) assessed using MRI predicts increasing disability and has, by inference, been proposed as an indirect index of axonal degeneration. However, the association between CSA and axonal loss, and their correlation with demyelination, have never been systematically investigated using human post mortem tissue. We extensively sampled spinal cords of seven women and six men with multiple sclerosis (mean disease duration= 29 years) and five healthy controls to quantify axonal density and its association with demyelination and CSA. 396 tissue blocks were embedded in paraffin and immuno-stained for myelin basic protein and phosphorylated neurofilaments. Measurements included total CSA, areas of (i) lateral cortico-spinal tracts, (ii) gray matter, (iii) white matter, (iv) demyelination, and the number of axons within the lateral cortico-spinal tracts. Linear mixed models were used to analyze relationships. In multiple sclerosis CSA reduction at cervical, thoracic and lumbar levels ranged between 19 and 24% with white (19-24%) and gray (17-21%) matter atrophy contributing equally across levels. Axonal density in multiple sclerosis was lower by 57-62% across all levels and affected all fibers regardless of diameter. Demyelination affected 24-48% of the gray matter, most extensively at the thoracic level, and 11-13% of the white matter, with no significant differences across levels. Disease duration was associated with reduced axonal density, however not with any area index. Significant association was detected between focal demyelination and decreased axonal density. In conclusion, over nearly 30 years multiple sclerosis reduces axonal density by 60% throughout the spinal cord. Spinal cord cross sectional area

Prevalence of multiple sclerosis in Denmark 1950-2005

DEFF Research Database (Denmark)

Bentzen, Joan; Meulengracht Flachs, Esben; Stenager, Egon

2010-01-01

Multiple sclerosis is an inflammatory disease of the central nervous system of unknown aetiology. Its prevalence varies by ethnicity and place: persons of northern European descent are at increased risk while persons living at lower latitudes appear to be protected against the disease. The Danish...... Multiple Sclerosis Registry is a national registry established in 1956 after a population-based survey which receives information from numerous sources. It is considered to be more than 90% complete, with a validity of 94%. Using data from the Registry, we calculated prevalences per 100,000 inhabitants....... The standardized prevalence of multiple sclerosis increased from 58.8 (95% confidence interval: 54.9-62.7) in 1950 to 154.5 per 100,000 (95% confidence interval: 148.8-160.2) in 2005, and the female to male ratio increased from 1.31 in 1950 to 2.02 in 2005. The increase in prevalence is due to both increased...

Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

Directory of Open Access Journals (Sweden)

Tobias Ruck

2015-07-01

Full Text Available Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52 and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.

Magnetic resonance imaging in multiple sclerosis

International Nuclear Information System (INIS)

Kesselring, J.; Ormerod, I.E.C.; Miller, D.H.; Du Boulay, G.H.; McDonald, W.I.

1989-01-01

In 1983 the Multiple Sclerosis Society of Great Britain and Northern Ireland set up the Multiple Sclerosis NMR Research Group at the Institute of Neurology and the National Hospital, Queen Square. The first aim of the Group was to define the role of MRI in the diagnosis and differential diagnosis of multiple sclerosis, and this Atlas represents a summary of that work. Our strategy was to determine the pattern of MRI abnormalities in clinically definite MS and to compare it with those of isolated clinical syndromes of the kind seen in MS (e.g. optic neuritis) and of other disorders with which MS can be confused clinically or radiologically. We have also been involved in a major program of experimental work designed to elucidate the origin of the abnormal signals in MRI. To describe this in full detail would go beyond the scope of the Atlas, but we have incorporated such results as far as they illuminate our clinical problems. The imager used was a 0.5 Tesla Picker superconducting system. Technical advances have been rapid since we began. Nevertheless, the quality of the images obtained at our relatively low field has enabled us to establish the patterns of abnormality in the brain in MS and the diseases which must be distinguished from it. (orig./MG)

The use of valproic acid and multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, Nete Munk; Svanström, Henrik; Stenager, Egon

2014-01-01

BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect. OBJECTIVE...... current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44-3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an intention-to-treat analysis...

The danish multiple sclerosis registry

DEFF Research Database (Denmark)

Brønnum-Hansen, Henrik; Koch-Henriksen, Nils; Stenager, Egon

2011-01-01

Introduction: The Danish Multiple Sclerosis (MS) Registry was established in 1956. Content: The register comprises data on all Danes who had MS in 1949 or who have been diagnosed since. Data on new cases and updated information on persons with an MS diagnosis already notified are continuously...

Circulating IGF-1, IGFB-3, GH and TSH levels in multiple sclerosis and their relationship with treatment.

Science.gov (United States)

Akcali, Aylin; Bal, Berrin; Erbagci, Binnur

2017-07-01

Improving the proficiency of oligodendrocytes in their ability to repair myelin damage is one of the major goals of multiple sclerosis treatment. Insulin-like growth factor-1 (IGF-1) is one of several polypeptides that are considered to have potential benefits in that sense. In the present study, we aimed to determine serum levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3), thyroid stimulating hormone (TSH) and growth hormone (GH) among treated and non-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and a healthy control group. The study enrolled 100 RRMS patients and 100 age- and sex-matched control subjects diagnosed with definite multiple sclerosis (MS). Serum GH, IGF-1, IGFBP-3, and TSH levels were studied. The number of relapses and Expanded Disability Status Scale were negatively correlated and IGFBP-3 and GH were positively correlated with IGF-1. A statistically significant difference was not observed when patients were divided into two subgroups as patients treated with a MS-specific therapy (n = 54) and non-treated patients (n = 46). TSH and IGFBP-3 values were significantly lower in patient group vs. While no difference was determined with in IGF-1 levels, low levels of IGF-1 was in correlation with the least levels of IGFBP-3. To understand the relation between IGF-1 and IGFBP-3, the role of low levels of IGFBP-3 and TSH may be studied with clinic isolated syndrome patients and the evolution of these patients to definite MS.

Treatment patterns in disease-modifying therapy for patients with multiple sclerosis in the United States.

Science.gov (United States)

Bonafede, Machaon M; Johnson, Barbara H; Wenten, Madé; Watson, Crystal

2013-10-01

Patients with multiple sclerosis (MS) whose disease activity is inadequately controlled with a platform therapy (interferon beta or glatiramer acetate [GA]) may switch to another platform therapy or escalate therapy to natalizumab or fingolimod, which were approved in the US in 2006 and 2010, respectively. The objective of this study was to describe treatment patterns in patients with multiple sclerosis (MS) in the United States who were followed for 2 years after initiating a disease-modifying therapy (DMT). A retrospective observational cohort study was conducted to examine treatment patterns of initial DMT use (on initial therapy for 2 years with and without gaps of ≥ 60 days, medication switching, and discontinuation) among patients with MS who initiated a platform therapy (interferon-β or glatiramer acetate) or natalizumab between January 1, 2007, and September 30, 2009; the first DMT claim was the index. Eligible patients were identified in the MarketScan Commercial and Medicare Supplemental databases based on continuous enrollment for 6 months before (preindex period) and 24 months after their index date, with a diagnosis of MS and no claim for a previous DMT in the 6-month preindex period. Demographics at index and clinical characteristics during the preindex period were also analyzed. A total of 6181 MS patients were included, with 5735 (92.8%) starting on platform therapy. Natalizumab initiators were more likely to stay on index therapy (32.3% vs 16.9%, P treatment gaps of ≥ 60 days (44.8% vs 55.3%, P treatment (13.9% vs 19.1%, P = 0.007) and took longer to switch (400.9 days vs 330.7 days, P treatment gaps, and switch less than platform initiators in the 2 years after treatment initiation. Switching between platform therapies is common despite evidence that MS patients on platform therapy may benefit from switching to natalizumab. © 2013 Elsevier HS Journals, Inc. All rights reserved.

MR in the diagnosis and monitoring of multiple sclerosis: An overview

International Nuclear Information System (INIS)

Rovira, Alex; Leon, Adelaida

2008-01-01

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

MR in the diagnosis and monitoring of multiple sclerosis: An overview

Energy Technology Data Exchange (ETDEWEB)

Rovira, Alex [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)], E-mail: alex.rovira@idi-cat.org; Leon, Adelaida [Magnetic Resonance Unit (I.D.I.), Department of Radiology, Hospital Universitari Vall d' Hebron, Barcelona (Spain)

2008-09-15

Multiple sclerosis is a chronic, persistent inflammatory-demyelinating disease of the central nervous system that typically presents as an acute clinically isolated syndrome attributable to a monofocal or multifocal demyelinating lesion, which usually affects the optic nerve, spinal cord, or brainstem and cerebellum. Although the diagnosis of multiple sclerosis is still based on clinical findings, magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Conventional magnetic resonance imaging techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences are highly sensitive in detecting multiple sclerosis plaques and provide a quantitative assessment of inflammatory activity and lesion load. However, there is a persisting mismatch between clinical and magnetic resonance imaging efficacy of approved treatments, which underlies the fact that this technique does not suffice to explain the entire spectrum of the disease process. In recent years, great effort has been dedicated to overcoming these limitations by using non-conventional magnetic resonance-derived metrics that can selectively measure the more destructive aspects of multiple sclerosis pathology and monitor the reparative mechanisms. These metrics, which include unenhanced T1-weighted imaging, measures of central nervous system atrophy, magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion-weighted imaging, and functional magnetic resonance imaging, provide a better approximation of the pathological substrate of the multiple sclerosis plaques, have increased our understanding of the pathogenesis of the disease, and have proven useful for studying the natural history of multiple sclerosis and monitoring the effects of new treatments. Therefore, magnetic resonance imaging not only plays an

The diagnosis of multiple sclerosis

International Nuclear Information System (INIS)

Sanders, E.A.C.M.

1982-01-01

This thesis describes recently developed research methods for the diagnosis of multiple sclerosis. In Chapter X the use of the CT-scan in the detection of hemispheral or cerebellar lesions is discussed. In chapter XIII the results of the application of all methods to a group of 89 patients with definite, probable or possible multiple sclerosis and to a group of 25 purely optic neuritis patients are presented. With the aid of the CT-scan, hypo- or hyperdense areas in the white matter of the cerebral hemispheres were found in 52% of the 114 patients. Most reports ascribe these lesions to demyelinating cerebral plaques. The CT-scan showed no cerebellar or brainstem lesions. The CT-scan is independent of the duration of, and degree of incapacitation due to, the disease and can be helpful in giving a definite diagnosis in an early stage of the disease. The CT-scan will always play an important role for the differential diagnosis. (Auth.)

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study.

Directory of Open Access Journals (Sweden)

Doriana Landi

Full Text Available Flu-like syndrome (FLS is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS treated with interferon beta (IFNβ. FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6 in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.We conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2 first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS] after 4 weeks of treatment within each sequence.Forty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference -0.15; 95% confidence interval: from -0.74 to 0.44; p = 0.6029. The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.The addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFN�

Neural correlates of alerting and orienting impairment in multiple sclerosis patients.

Science.gov (United States)

Vázquez-Marrufo, Manuel; Galvao-Carmona, Alejandro; González-Rosa, Javier J; Hidalgo-Muñoz, Antonio R; Borges, Mónica; Ruiz-Peña, Juan Luis; Izquierdo, Guillermo

2014-01-01

A considerable percentage of multiple sclerosis patients have attentional impairment, but understanding its neurophysiological basis remains a challenge. The Attention Network Test allows 3 attentional networks to be studied. Previous behavioural studies using this test have shown that the alerting network is impaired in multiple sclerosis. The aim of this study was to identify neurophysiological indexes of the attention impairment in relapsing-remitting multiple sclerosis patients using this test. After general slowing had been removed in patients group to isolate the effects of each condition, some behavioral differences between them were obtained. About Contingent Negative Variation, a statistically significant decrement were found in the amplitude for Central and Spatial Cue Conditions for patient group (pmultiple sclerosis. P1 and N1 delayed latencies are evidence of the demyelination process that causes impairment in the first steps of the visual sensory processing. Lastly, P3 amplitude shows a general decrease for the pathological group probably indexing a more central impairment. These results suggest that the Attention Network Test give evidence of multiple levels of attention impairment, which could help in the assessment and treatment of relapsing-remitting multiple sclerosis patients.

Total lymphoid irradiation for multiple sclerosis

International Nuclear Information System (INIS)

Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

1988-01-01

Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one

Effect of 12-Week Pilates Trainning on EDSS in Women Suffering fromMultiple Sclerosis

OpenAIRE

Z Shanazari; SM Marandi; S Samie

2013-01-01

Abstract Background & aim: Multiple sclerosis is a debilitating disease that strikes the immune system. Multiple sclerosis is a chronic disease which debilitates the nervous system. The study was evaluated the effects of Pilates exercise on women with physical disabilities suffering from multiple sclerosis for 12 weeks .The aim of this study was to investigating the effects of Pilates trainning on EDSS of women suffering from Multiple Sclerosis (MS) for 12 weeks. Methods: In the pres...

Orthodontic treatment for a patient with multiple sclerosis

Science.gov (United States)

Bakathir, Manal A

2017-01-01

Multiple sclerosis (MS) is a chronic, autoimmune inflammatory disorder of the central nervous system (CNS) that affects myelinated axons, destroying the myelin and damaging axons to varying degrees. The course of MS is highly varied and unpredictable. Metals used during orthodontic treatment can negatively affect imaging techniques used to diagnose and monitor the progression of MS, while medications used to treat MS can negatively affect orthodontic tooth movement. The present case report highlights some of the challenges encountered during orthodontic treatment of a patient with MS and how to overcome them. The patient was a 20-year-old woman with complaints of diastema and spacing in the upper arch. Although closing the spaces was challenging due to some of the MS medications, she was treated successfully, without complications, within 20 months using closing loops. PMID:28717636

Glomerular Filtration Rate in Patients with Multiple Sclerosis Undergoing Stem Cell Transplantation and Treated With Cyclophosphamide.

Science.gov (United States)

Ruiz-Argüelles, Alejandro; Gastélum-Cano, Jose M; Méndez-Huerta, Mariana A; Rodríguez-Gallegos, Alma B; Ruiz-Argüelles, Guillermo J

2018-06-15

Glomerular filtration rate (GFR) is partially impaired in patients with multiple sclerosis (MS). When given chemotherapy before receiving hematopoietic stem-cell transplantation, GFR might be further deteriorated. To measure the effect of cyclophosphamide on GFR in patients with MS who undergo chemotherapy. We estimated GFR based on creatinine and cystatin C plasma concentrations in patients undergoing autologous hematopoietic stem-cell transplantation to treat their MS. Baseline GFR values were lower in the 28 patients with MS than in the 20 healthy individuals. Also, according to the Chronic Kidney Disease-Epidemiology Collaborative Group (CKD-EPI) 2012 Creat-CysC equation criteria, 4 of 28 patients were classified as having chronic kidney disease (CKD) before receiving the chemotherapy drugs. After receiving 4 × 50 mg per kg body weight cyclophosphamide, abnormal GFR results were recorded in 12 of 28 patients. Renal function must be monitored in patients with MS undergoing autologous stem-cell transplantation. Also, chemotherapy should be constrained as much as possible to prevent further deterioration of renal function.

Clinical diagnostic criteria of multiple sclerosis: the role of magnetic resonance imaging

International Nuclear Information System (INIS)

Belair, M.; Girard, M.

2004-01-01

The objective of this article is to summarize the diagnostic criteria recommended by the International Panel on the Diagnosis of Multiple Sclerosis in 2001. The recommendations of another working group, the Consortium of Multiple Sclerosis Centers Consensus Meeting, which met in Vancouver in 2001, concerning the diagnosis and follow-up of patients with multiple sclerosis are also presented in an effort to standardize the protocols for magnetic resonance imaging of these patients. (author)

The effect of interferon-β on mouse neural progenitor cell survival and differentiation

International Nuclear Information System (INIS)

Hirsch, Marek; Knight, Julia; Tobita, Mari; Soltys, John; Panitch, Hillel; Mao-Draayer, Yang

2009-01-01

Interferon-β (IFN-β) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-β on the central nervous system (CNS) are not well understood. To determine whether IFN-β has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-β and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFNα/β receptor (IFNAR). In response to IFN-β treatment, no effect was observed on differentiation or proliferation. However, IFN-β treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-β treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-β can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

The effect of interferon-{beta} on mouse neural progenitor cell survival and differentiation

Energy Technology Data Exchange (ETDEWEB)

Hirsch, Marek [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Knight, Julia [Neuroscience Department, University of Vermont College of Medicine, Burlington, VT (United States); Tobita, Mari; Soltys, John; Panitch, Hillel [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States); Mao-Draayer, Yang, E-mail: yang.mao-draayer@vtmednet.org [Neurology Department, University of Vermont College of Medicine, Burlington, VT (United States)

2009-10-16

Interferon-{beta} (IFN-{beta}) is a mainstay therapy for relapse-remitting multiple sclerosis (MS). However, the direct effects of IFN-{beta} on the central nervous system (CNS) are not well understood. To determine whether IFN-{beta} has direct neuroprotective effects on CNS cells, we treated adult mouse neural progenitor cells (NPCs) in vitro with IFN-{beta} and examined the effects on proliferation, apoptosis, and differentiation. We found that mouse NPCs express high levels of IFN{alpha}/{beta} receptor (IFNAR). In response to IFN-{beta} treatment, no effect was observed on differentiation or proliferation. However, IFN-{beta} treated mouse NPCs demonstrated decreased apoptosis upon growth factor withdrawal. Pathway-specific polymerase chain reaction (PCR) arrays demonstrated that IFN-{beta} treatment upregulated the STAT 1 and 2 signaling pathway, as well as GFRA2, NOD1, Caspases 1 and 12, and TNFSF10. These results suggest that IFN-{beta} can directly affect NPC survival, possibly playing a neuroprotective role in the CNS by modulating neurotrophic factors.

Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

Science.gov (United States)

Miller, Aaron E

2015-10-01

The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P treatment are recommended to assess potential safety issues. Women of childbearing potential must use effective contraception and, in the event of pregnancy, undergo an accelerated elimination procedure to reduce plasma concentrations of teriflunomide. Clinical evidence suggests that teriflunomide is an effective therapeutic choice for patients with RMS, both as an initial treatment and as an alternative for patients who may have experienced intolerance or inadequate response to a previous or current disease-modifying therapy. Copyright © 2015 The Authors

Recent advances in multiple sclerosis therapy

International Nuclear Information System (INIS)

Gonsette, R.E.; Delmotte, P.

1989-01-01

Seven papers in this volume are in INIS scope, one dealing with autoradiographic detection of multiple sclerosis plaques with radiologands, and the others with magnetic resonance imaging of MS lesions. (H.W.). refs.; figs.; tabs

Nicotinic Acid-Mediated Activation of Both Membrane and Nuclear Receptors towards Therapeutic Glucocorticoid Mimetics for Treating Multiple Sclerosis

Directory of Open Access Journals (Sweden)

W. Todd Penberthy

2009-01-01

Full Text Available Acute attacks of multiple sclerosis (MS are most commonly treated with glucocorticoids, which can provide life-saving albeit only temporary symptomatic relief. The mechanism of action (MOA is now known to involve induction of indoleamine 2,3-dioxygenase (IDO and interleukin-10 (IL-10, where IL-10 requires subsequent heme oxygenase-1 (HMOX-1 induction. Ectopic expression studies reveal that even small changes in expression of IDO, HMOX-1, or mitochondrial superoxide dismutase (SOD2 can prevent demyelination in experimental autoimmune encephalomyelitis (EAE animal models of MS. An alternative to glucocorticoids is needed for a long-term treatment of MS. A distinctly short list of endogenous activators of both membrane G-protein-coupled receptors and nuclear peroxisome proliferating antigen receptors (PPARs demonstrably ameliorate EAE pathogenesis by MOAs resembling that of glucocorticoids. These dual activators and potential MS therapeutics include endocannabinoids and the prostaglandin 15-deoxy-Δ12,14-PGJ2. Nicotinamide profoundly ameliorates and prevents autoimmune-mediated demyelination in EAE via maintaining levels of nicotinamide adenine dinucleotide (NAD, without activating PPAR nor any G-protein-coupled receptor. By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPAR-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Thus nicotinic acid is uniquely suited for providing therapeutic relief in MS. However nicotinic acid is unexamined in MS research. Nicotinic acid penetrates the blood brain barrier, cures pellagric dementia, has been used for over 50 years clinically without toxicity, and raises HDL concentrations to a greater degree than any pharmaceutical, thus providing unparalleled benefits against lipodystrophy. Summary analysis reveals that the expected therapeutic benefits of high-dose nicotinic

Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

Science.gov (United States)

Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

2015-01-01

Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

Male factor infertility and risk of multiple sclerosis

DEFF Research Database (Denmark)

Glazer, Clara Helene; Tøttenborg, Sandra Søgaard; Giwercman, Aleksander

2018-01-01

and prevalent as well as incident MS. METHOD: Our cohort was established by linkage of the Danish National in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry and consisted of 51,063 men whose partners had undergone fertility treatment in all public and private fertility clinics......BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no studies have evaluated whether male infertility is associated with MS. OBJECTIVE: To study the association between male factor infertility...

Cesarean section and offspring's risk of multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, Nete M; Bager, Peter; Stenager, Egon

2013-01-01

Apart from a recent study reporting a 2- to 3-fold increased risk of multiple sclerosis (MS) among women and men who were delivered by Cesarean section (C-section), little attention has been given to the possible association between mode of delivery and the risk of MS.......Apart from a recent study reporting a 2- to 3-fold increased risk of multiple sclerosis (MS) among women and men who were delivered by Cesarean section (C-section), little attention has been given to the possible association between mode of delivery and the risk of MS....

Vision and vision-related outcome measures in multiple sclerosis

DEFF Research Database (Denmark)

Balcer, Laura J; Miller, David H; Reingold, Stephen C

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple...... sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique...... of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes...

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

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Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Physical activity motivation and benefits in people with multiple sclerosis.

Science.gov (United States)

Fasczewski, Kimberly S; Gill, Diane L; Rothberger, Sara M

2018-06-01

Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic

The low EOMES/TBX21 molecular phenotype in multiple sclerosis reflects CD56+ cell dysregulation and is affected by immunomodulatory therapies.

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McKay, Fiona C; Gatt, Prudence N; Fewings, Nicole; Parnell, Grant P; Schibeci, Stephen D; Basuki, Monica A I; Powell, Joseph E; Goldinger, Anita; Fabis-Pedrini, Marzena J; Kermode, Allan G; Burke, Therese; Vucic, Steve; Stewart, Graeme J; Booth, David R

2016-02-01

Multiple Sclerosis (MS) is an autoimmune disease treated by therapies targeting peripheral blood cells. We previously identified that expression of two MS-risk genes, the transcription factors EOMES and TBX21 (ET), was low in blood from MS and stable over time. Here we replicated the low ET expression in a new MS cohort (p<0.0007 for EOMES, p<0.028 for TBX21) and demonstrate longitudinal stability (p<10(-4)) and high heritability (h(2)=0.48 for EOMES) for this molecular phenotype. Genes whose expression correlated with ET, especially those controlling cell migration, further defined the phenotype. CD56+ cells and other subsets expressed lower levels of Eomes or T-bet protein and/or were under-represented in MS. EOMES and TBX21 risk SNP genotypes, and serum EBNA-1 titres were not correlated with ET expression, but HLA-DRB1*1501 genotype was. ET expression was normalised to healthy control levels with natalizumab, and was highly variable for glatiramer acetate, fingolimod, interferon-beta, dimethyl fumarate. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

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Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with

Infectious mononucleosis-linked HLA class I single nucleotide polymorphism is associated with multiple sclerosis.

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Jafari, Naghmeh; Broer, Linda; Hoppenbrouwers, Ilse A; van Duijn, Cornelia M; Hintzen, Rogier Q

2010-11-01

Multiple sclerosis is a presumed autoimmune disease associated with genetic and environmental risk factors such as infectious mononucleosis. Recent research has shown infectious mononucleosis to be associated with a specific HLA class I polymorphism. Our aim was to test if the infectious mononucleosis-linked HLA class I single nucleotide polymorphism (rs6457110) is also associated with multiple sclerosis. Genotyping of the HLA-A single nucleotide polymorphism rs6457110 using TaqMan was performed in 591 multiple sclerosis cases and 600 controls. The association of multiple sclerosis with the HLA-A single nucleotide polymorphism was tested using logistic regression adjusted for age, sex and HLA-DRB1*1501. HLA-A minor allele (A) is associated with multiple sclerosis (OR = 0.68; p = 4.08 × 10( -5)). After stratification for HLA-DRB1*1501 risk allele (T) carrier we showed a significant OR of 0.70 (p = 0.003) for HLA-A. HLA class I single nucleotide polymorphism rs6457110 is associated with infectious mononucleosis and multiple sclerosis, independent of the major class II allele, supporting the hypothesis that shared genetics may contribute to the association between infectious mononucleosis and multiple sclerosis.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis

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Bo Young Choi

2017-09-01

Full Text Available Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS, such as matrix metallopeptidase 9 (MMP-9 activation, blood-brain barrier (BBB disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 (ZnT3 knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

The Emerging Role of Zinc in the Pathogenesis of Multiple Sclerosis.

Science.gov (United States)

Choi, Bo Young; Jung, Jong Won; Suh, Sang Won

2017-09-28

Our lab has previously demonstrated that multiple sclerosis-induced spinal cord white matter damage and motor deficits are mediated by the pathological disruption of zinc homeostasis. Abnormal vesicular zinc release and intracellular zinc accumulation may mediate several steps in the pathophysiological processes of multiple sclerosis (MS), such as matrix metallopeptidase 9 (MMP-9) activation, blood-brain barrier (BBB) disruption, and subsequent immune cell infiltration from peripheral systems. Oral administration of a zinc chelator decreased BBB disruption, immune cell infiltration, and spinal white matter myelin destruction. Therefore, we hypothesized that zinc released into the extracellular space during MS progression is involved in destruction of the myelin sheath in spinal cord white mater and in generation of motor deficits. To confirm our previous study, we employed zinc transporter 3 ( ZnT3 ) knockout mice to test whether vesicular zinc depletion shows protective effects on multiple sclerosis-induced white matter damage and motor deficits. ZnT3 gene deletion profoundly reduced the daily clinical score of experimental autoimmune encephalomyelitis (EAE) by suppression of inflammation and demyelination in the spinal cord. ZnT3 gene deletion also remarkably inhibited formation of multiple sclerosis-associated aberrant synaptic zinc patches, MMP-9 activation, and BBB disruption. These two studies strongly support our hypothesis that zinc release from presynaptic terminals may be involved in multiple sclerosis pathogenesis. Further studies will no doubt continue to add mechanistic detail to this process and with luck, clarify how these observations may lead to development of novel therapeutic approaches for the treatment of multiple sclerosis.

Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

Science.gov (United States)

Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

2018-07-01

Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple

Ketamine Therapy for Treatment-resistant Depression in a Patient with Multiple Sclerosis: A Case Report.

Science.gov (United States)

Messer, Michael M; Haller, Irina V

2017-01-01

Objective: Depression is a common condition among patients with multiple sclerosis and often becomes resistant to oral antidepressants. We report a patient with multiple sclerosis who developed severe treatment-resistant depression and who was successfully treated with intravenous ketamine over the period of two years. Methods: Ketamine treatment protocol included an initial series of six treatments administered every other day, followed by a maintenance schedule. Ketamine was administered intravenously at 0.5mg/kg of ideal body weight over 40 minutes. Depression symptoms were measured using Beck Depression Index. Results: The patient's Beck Depression Index score prior to initiating ketamine treatment was 38, corresponding to severe depression. Response to treatment, defined as 50-percent reduction in Beck Depression Index score, was observed after five treatments. For this patient, the maintenance schedule ranged from a weekly treatment to one treatment every three weeks. During the two-year observation period, this patient was able to maintain a stable non-depressed mood and had no worsening of her MS symptoms. Conclusion: Ketamine may be an alternative treatment for resistant depression and may have a special use in patients with multiple sclerosis.

SOME NEUROCHEMICAL DISTURBANCES IN MULTIPLE SCLEROSIS

Directory of Open Access Journals (Sweden)

Vladimir V. Markelov

2006-04-01

Full Text Available ABSTRACTThe data presented in this manuscript suggest a pivotal role of the central nervous system (CNS in the regulation of immune status. We describe here that some neurochemical disturbances may provoke development of various diseases including multiple sclerosis. Some theoretic and practical backgrounds, how to improve the multiple sclerosis sufferers and patients with other autoimmune disorders, are also given.RESUMENLos datos que presentamos en este manuscrito, sugieren un papel guia del sistema nervioso central (SNC en la regulación del estado inmune. Describimos aquí que varias alteraciones neuroquímicas pueden provocar el desarrollo de varias enfermedades, incluyendo esclerosis múltiple. También se comenta acerca del trasfondo teórico y práctico, y cómo mejorar a víctimas y pacientes con esclerosis múltiple y otras alteraciones autoinmunes.

Serum Homocysteine level in patients with Multiple Sclerosis

Directory of Open Access Journals (Sweden)

F Ashtari

2005-09-01

Full Text Available Background: The etiology of multiple sclerosis (MS, a chronic demyelinative disease-is unknown. The damage of blood–brain barrier (BBB vasculature is a characteristic of MS and Homocystein (Hcy can damage BBB, then increase in total Hcy may be important in MS pathogenesis. The aim of this study was to compare the serum level of total Hcy in MS patients with control group. Methods: In a case control study, serum level of total Hcy measured in 35 MS patient and compared with 30 healthy matched controls. All patients had definitive MS according to Poser criteria, without history of myocardial infarction, stroke, neuropathy, transient ischemic attack, homocystinuria or renal failure. Results: The serum concentration of total homocystein was significantly higher in multiple sclerosis patients than healthy controls. The mean total Hcy level was 17.92± 6.9 mmol/lit in cases and 14.6±2.92 mmol/lit in controls (P=0.013. Conclusion: Serum total Homocystein may have a role in MS pathogenesis and reduction of it should be studied moreover. Key words: Multiple Sclerosis, Homocystein, Serum level

Soluble Receptor for Advanced Glycation End Products (sRAGE is Up-Regulated in Multiple Sclerosis Patients Treated with Interferon β-1a

Directory of Open Access Journals (Sweden)

Mahnoosh Rahimi

2018-03-01

Full Text Available Background/Aims: Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system. Considering the role of immune system in its pathogenesis, researchers have focused on evaluation of the expression of immune-related genes or proteins in MS patients. Among proteins whose participation in inflammatory process has been documented is the receptor for advanced glycation end products (RAGE. Methods: In the present study, we compared RAGE transcript levels by means of quantitative real-time PCR as well as the serum level of soluble RAGE (sRAGE by means of enzyme- linked immunosorbent assay (ELISA in 50 IFNβ-1a responsive relapsing-remitting MS patients when compared with age and sex-matched healthy subjects. Results: Elevated expression of RAGE as well as higher levels of sRAGE were detected in IFN-β responsive MS patients compared with the controls. A significant inverse correlation between sRAGE plasma concentrations and the expanded disability status scale (EDSS was also detected in which each unit of increase in sRAGE level resulted in a 0.308 unit decrease in EDSS. Conclusion: Considering the stable clinical state of the MS patients in this study and their response to IFNβ-1a, the elevated levels of sRAGE in patients compared with healthy subjects could be related to the effects of this kind of treatment.

DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

The Danish Multiple Sclerosis Registry. History, data collection and validity

DEFF Research Database (Denmark)

Koch-Henriksen, N; Rasmussen, S; Stenager, E

2001-01-01

The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry...... instrument for monitoring incidence and prevalence, analysing survival, performing genetic analysis, providing unselected patient samples for clinical analyses, performing case-control studies and prospective studies and estimating the need for treatment and care....

Respiratory muscle training for multiple sclerosis

NARCIS (Netherlands)

Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.

2017-01-01

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and

[Multiple sclerosis in literature, cinema and television].

Science.gov (United States)

Collado-Vazquez, S; Carrillo, J M; Cano-de-la-Cuerda, R

2016-12-16

Today, the care of patients with multiple sclerosis and those around them represents a clinical and therapeutic challenge for healthcare professionals. The aim of this study is to analyse the appearance of multiple sclerosis in literature, cinema and television, and to reflect upon the image it has in these media. Several representative works that have addressed multiple sclerosis were reviewed, and many of them were seen to offer a very true-to-life vision of the disease. Likewise, a review was also conducted of the most relevant films and TV series that, on occasions, offer the general public a close look at the impact of the disease on patients or relatives, although they are sometimes somewhat exaggerated for the sake of increased dramatic effect and offer a slightly distorted view of reality. Literature largely reflects the real epidemiology, the symptoms and development of the disease, while less attention seems to be given to the diagnostic and therapeutic options open to patients. Cinema and television have offered a correct image but sometimes with the addition of more dramatic effects. It is important for literature, cinema and television to offer a realistic view of this neurological disease so as to make it better known among the public and to help lessen the stigma attached to it.

Plasma homocysteine levels in multiple sclerosis

NARCIS (Netherlands)

Ramsaransing, G S M; Fokkema, M R; Teelken, A; Arutjunyan, A V; Koch, M; De Keyser, J

Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether

Brain atrophy and lesion load predict long term disability in multiple sclerosis

DEFF Research Database (Denmark)

Popescu, Veronica; Agosta, Federica; Hulst, Hanneke E

2013-01-01

To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).......To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS)....

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study

NARCIS (Netherlands)

D. Buljevac (Dragan); W.C.J. Hop (Wim); W. Reedeker; A.C.J.W. Janssens (Cécile); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter); R.Q. Hintzen (Rogier)

2003-01-01

textabstractOBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of

5HT(4) agonists inhibit interferon-gamma-induced MHC class II and B7 costimulatory molecules expression on cultured astrocytes

NARCIS (Netherlands)

Zeinstra, Esther M.; Wilczak, Nadine; Wilschut, Jan C.; Glazenburg, Lisa; Chesik, Daniel; Kroese, Frans G. M.; De Keyser, Jacques

2006-01-01

A failure of tight control of MHC class II expression on astrocytes may play a role in the development of autoimmune responses in multiple sclerosis. The 5-HT4 serotonin receptor agonists cisapride and prucalopride, at concentrations between 10(-10) M and 10(-8) M, reduced interferon-gamma-induced

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

Science.gov (United States)

Fujiwara, E; Kmech, J A; Cobzas, D; Sun, H; Seres, P; Blevins, G; Wilman, A H

2017-05-01

Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures. Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions. Compared with controls, patients showed reduced memory ( P processing speed ( P = .02) and smaller putamen ( P deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis. © 2017 by American Journal of Neuroradiology.

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis.

Directory of Open Access Journals (Sweden)

Caterina Motta

Full Text Available The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive.To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis.A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E defined as the sum of sROMs was proposed.We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status.Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis.

The Combined Effects of Training on Serum Levels of Interferon Gamma (INF-γ and Expanded Scale Disability Status Scale of Patients with Multiple Sclerosis at Different Levels of Disability

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Z Saberi

2017-02-01

Full Text Available Background and aim: Multiple sclerosis is a chronic and debilitating nervous system, leading to demyelination of the central nervous system (brain and spinal cord. Regular exercise and general physical activity is important to maintain health and prevent disease, already well known. Therefore the aim of this study was to evaluate the effect of 12 weeks of combined exercises (strength training, Strengthening Exercises, cardio respiratory endurance, a variety of static and dynamic balance exercises, exercises of the trunk (pilates training and walking on the treadmill training with body weight support on interferon gamma and Expanded Disability Status Scale women with multiple sclerosis. Methods: In the present experimental rsearch, female patients who were admitted to the MS Society of Shahrekord, Iran, were divided into three groups based on physical disability scores. In the first group (physical disability scale less than 4.5, 44 people were randomly selected to one experimental group (22 patients and control group (n = 22. In the second group (scale physical disability between 5 and 5.6, 26 patients were enrolled and randomly assigned to an experimental group (n = 13 and control group (n = 13. The third (Physical Disability Scale-up to 6.5, 26 patients were enrolled and randomly assigned to an experimental group (n = 13 and control group (n = 13. A total of 96 patients were participated in this study. Experimental groups of first, second and third were done its own intervention separately. While the control group received stretching exercises, workout schedule for the experimental group was of 12 weeks, three sessions of lasted one hour. Anthropometric factors and interferon-gamma were measured before and after training with the appropriate tools. Serum levels of INF-γ was determind using a commercial ELISA kit and EDSS scores were measured using the measure of disability in patients with MS. Data analysis was performed using descriptive

Treatment of Multiple Sclerosis

OpenAIRE

Bošnjak-Pašić, Marija; Vidrih, Branka; Miškov, Snježana; Demarin, Vida

2009-01-01

Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system, characterized by multifocal inflammatory destruction of myelin, axonal damage and loss of oligodendrocytes. The disease is carried through two stages: inflammatory and degenerative. The most common form of disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The treatment of MS is divided into: treatment of the acute phase of illness, prevention of new relapses and di...

Multiple sclerosis: Left advantage for auditory laterality in dichotic tests of central auditory processing and relationship of psychoacoustic tests with the Multiple Sclerosis Disability Scale-EDSS.

Science.gov (United States)

Peñaloza López, Yolanda Rebeca; Orozco Peña, Xóchitl Daisy; Pérez Ruiz, Santiago Jesús

2018-04-03

To evaluate the central auditory processing disorders in patients with multiple sclerosis, emphasizing auditory laterality by applying psychoacoustic tests and to identify their relationship with the Multiple Sclerosis Disability Scale (EDSS) functions. Depression scales (HADS), EDSS, and 9 psychoacoustic tests to study CAPD were applied to 26 individuals with multiple sclerosis and 26 controls. Correlation tests were performed between the EDSS and psychoacoustic tests. Seven out of 9 psychoacoustic tests were significantly different (P<.05); right or left (14/19 explorations) with respect to control. In dichotic digits there was a left-ear advantage compared to the usual predominance of RDD. There was significant correlation in five psychoacoustic tests and the specific functions of EDSS. The left-ear advantage detected and interpreted as an expression of deficient influences of the corpus callosum and attention in multiple sclerosis should be investigated. There was a correlation between psychoacoustic tests and specific EDSS functions. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

International Nuclear Information System (INIS)

Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

1987-01-01

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases

Treatment adherence in multiple sclerosis: a survey of Belgian neurologists

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Decoo D

2015-11-01

Full Text Available Danny Decoo,1 Mathieu Vokaer2 1Department of Neurology and Neurorehab, AZ Alma, Sijsele, Belgium; 2Multiple Sclerosis Clinic, Edith Cavell Hospital, CHIREC group, Brussels, Belgium Background: Poor treatment adherence is common among patients with multiple sclerosis (MS. This survey evaluated neurologists’ perception of treatment adherence among MS patients.Materials and methods: This questionnaire-based survey of Belgian neurologists treating MS patients was conducted between June and July 2014. Face-to-face interviews with the neurologists were based on a semistructured questionnaire containing questions regarding the perception of the treatment-adherence level.Results: A total of 41 neurologists participated in the survey. Of these, 88% indicated frequent discussions about treatment adherence as beneficial for treatment efficacy. The mean time spent on the treatment-adherence discussion during the initial consultation was 11 minutes, with 24% of doctors spending 5 minutes and 24% of doctors spending 10 minutes discussing this issue. The majority of neurologists (56% perceived the adherence level in MS as good, and 12% perceived it as excellent. The majority of neurologists (64% indicated intolerance as a main cause of poor adherence, and all neurologists reported insufficient efficacy as a consequence of nonadherence. The importance of adherence in the neurologists’ practice was evaluated on a scale of 1–10, with 1= “not very important” and 10= “very important”: 44% of doctors indicated a score of 10, and the mean score was 9.0.Conclusion: Belgian neurologists consider treatment adherence in MS as essential for the benefits of therapies. However, although neurologists are aware of the consequences of nonadherence, they generally spend limited time discussing the importance of treatment adherence with their patients. Keywords: multiple sclerosis, treatment adherence, physician survey

Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

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Kurt-Wolfram Sühs

2016-09-01

Full Text Available Changes in cerebral lesion load by magnetic resonance imaging (MRI in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095 were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group.

Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

Science.gov (United States)

Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

2013-01-01

Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

Carnitine for fatigue in multiple sclerosis.

Science.gov (United States)

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2012-05-16

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active

Onset symptoms in paediatric multiple sclerosis

DEFF Research Database (Denmark)

Boesen, Magnus Spangsberg; Sellebjerg, Finn; Blinkenberg, Morten

2014-01-01

INTRODUCTION: Paediatric multiple sclerosis (MS) carries a relatively higher mortality and morbidity than adult MS. Paediatric MS symptoms and paraclinical findings at the first demyelinating event have never before been characterised in a Danish setting. The aim of this study was to compare...

Psychiatric co-morbidity in multiple sclerosis

DEFF Research Database (Denmark)

Hoang, Huong; Laursen, Bjarne; Stenager, Elsebeth N

2015-01-01

BACKGROUND: Studies of depression and anxiety in multiple sclerosis (MS) patients have reported higher rates in MS patients than the general population. OBJECTIVE: To estimate the risk of depression and anxiety and the use of tricyclic antidepressant and selective serotonin reuptake inhibitors...

Possibilities of computer tomography in multiple sclerosis

International Nuclear Information System (INIS)

Vymazal, J.; Bauer, J.

1983-01-01

Computer tomography was performed in 41 patients with multiple sclerosis, the average age of patients being 40.8 years. Native examinations were made of 17 patients, examinations with contrast medium of 19, both methods were used in the examination of 5 patients. In 26 patients, i.e. in almost two-thirds, cerebral atrophy was found, in 11 of a severe type. In 9 patients atrophy affected only the hemispheres, in 16 also the stem and cerebellum. The stem and cerebellum only were affected in 1 patient. Hypodense foci were found in 21 patients, i.e. more than half of those examined. In 9 there were multiple foci. In most of the 19 examined patients the hypodense changes were in the hemispheres and only in 2 in the cerebellum and brain stem. No hyperdense changes were detected. The value and possibilities are discussed of examinations by computer tomography multiple sclerosis. (author)

A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

DEFF Research Database (Denmark)

Jagodic, Maja; Colacios, Celine; Nohra, Rita

2009-01-01

Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

The clinical impact of cerebellar grey matter pathology in multiple sclerosis.

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Alfredo Damasceno

Full Text Available BACKGROUND: The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. OBJECTIVE: To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. METHODS: Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS and cerebellar functional system (FS score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT and the Symbol-Digit Modalities Test (SDMT. Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. RESULTS: After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001, cerebellar FS (p = 0.002, arm function (p = 0.049, and for leg function (p<0.001. Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013, while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015. CONCLUSIONS: Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

Group Positive Psychotherapy and Depression of Females Affected by Multiple Sclerosis

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Tayebeh Khayatan

2014-12-01

Full Text Available Objectives: Multiple Sclerosis is one of the most important and prevalent central nervous system diseases, causing disorders such as depression among affected patients. Positive psychotherapy is also a new approach that can be effective in reducing the depression of these people. This study aims to investigate the efficiency of group positive psychotherapy for decreasing the depression among females affected by Multiple Sclerosis. Methods: A samples of 30 females affected by Multiple Sclerosis with mild to moderate depression were participated, and were divided into two groups, intervention and control. Both groups completed Beck Depression Inventory II (BDI-II at the beginning, he intervention group received six sessions of positive psychotherapy. After the intervention both group completed the questionnaire again. Data was analyzed by descriptive and inferential statistical methods. Results: The result demonstrated that, the decline of depression was more in the intervention group than the control group. Moreover in the intervention group than control group, there was obtained significant reduction in both sub-scales of Beck Depression Inventory II. Discussion: Results of this study indicated that group positive psychotherapy is effective in reducing the depression of females affected by Multiple Sclerosis. This treatment can be widely used in the caring centers for treatment of people affected by Multiple Sclerosis and this can be justified because of its low cost and good efficiency.

Multiple sclerosis: general features and pharmacologic approach; Esclerosis multiple: aspectos generales y abordaje farmacologico

Energy Technology Data Exchange (ETDEWEB)

Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio [Instituto de Farmacia y Alimentos, Universidad de La Habana, La Habana (Cuba)

2009-07-01

Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

Science.gov (United States)

Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis

NARCIS (Netherlands)

Al-Izki, S.; Pryce, G.; Hankey, D.J.R.; Lidster, K.; von Kutzleben, S.M.; Browne, L.; Clutterbuck, L.; Posada, C.; Chan, A.W.E.; Amor, S.; Perkins, V.; Gerritsen, W.H.; Ummenthum, K.; Peferoen-Baert, R.; van der Valk, P.; Montoya, A.; Joel, S.P.; Garthwaite, J.; Giovannoni, G.; Selwood, D.L.; Baker, D.

2014-01-01

Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to

Optical Coherence Tomography-A New Diagnostic Tool to Evaluate Axonal Degeneration in Multiple Sclerosis: A Review

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Nilüfer Kale

2010-09-01

Full Text Available Multiple sclerosis is an inflammatory demyelinating disorder of the central nervous system with a wide spectrum of clinical signs and symptoms. Multiple sclerosis lesions have a predilection for the optic nerves, periventricular white matter, brainstem, spinal cord, and cerebellum. The mechanisms responsible for multiple sclerosis are complex and heterogeneous across patients and disease stages. No specific markers exist for the definite diagnosis and prognosis of multiple sclerosis. The afferent visual pathway, which extends from the retina to the primary visual cortex including the optic nerve, is one of the most commonly affected sites in multiple sclerosis (94-99%. Pathology of affected optic nerves exhibits inflammation, demyelination, gliosis, axonal injury, and thinning of the retinal nerve fiber layer (RNFL. The RNFL is composed of unmyelinated axons, and measuring RNFL thickness is a viable method to monitor axonal loss reflecting disease progression. Optical coherence tomography is a noninvasive and reproducible tool in assessing the impact of multiple sclerosis on the thickness of the RNFL. Assessment of the afferent visual pathway using clinical, imaging and electrophysiological methods provides insights into the pathophysiology of multiple sclerosis and may also serve a prognostic role in multiple sclerosis

The socioeconomic consequences of multiple sclerosis

DEFF Research Database (Denmark)

Jennum, Poul; Wanscher, Benedikte; Frederiksen, Jette

2012-01-01

Multiple sclerosis (MS) has serious negative effects on health-, social-, and work-related issues for the patients and their families, thus causing significant socioeconomic burden. The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national...

Rasch analysis of the Multiple Sclerosis Impact Scale (MSIS-29)

OpenAIRE

Ramp, Melina; Khan, Fary; Misajon, Rose Anne; Pallant, Julie F

2009-01-01

Abstract Background Multiple Sclerosis (MS) is a degenerative neurological disease that causes impairments, including spasticity, pain, fatigue, and bladder dysfunction, which negatively impact on quality of life. The Multiple Sclerosis Impact Scale (MSIS-29) is a disease-specific health-related quality of life (HRQoL) instrument, developed using the patient's perspective on disease impact. It consists of two subscales assessing the physical (MSIS-29-PHYS) and psychological (MSIS-29-PSYCH) im...

Midkine and multiple sclerosis

OpenAIRE

Takeuchi, Hideyuki

2014-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4+CD25+FoxP3+ regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the d...

Effects of Applying Hydrotherapy on Quality of Life in Women with Multiple Sclerosis

OpenAIRE

Somayyeh Ghaffari; Fazlollah Ahmadi; Seyyed Masoud Nabavi; Anoushirvan Kazem-Nezhad

2008-01-01

Objective: Multiple Sclerosis (MS) is one of the most common chronic diseases of the central nervous system (CNS), which causes important changes patient’s life, specially in adults life. MS decreases the quality of life (QOL) of patients severely and led to disability gradually. The aim of this study is to assess the effects of applying hydrotherapy on quality of life of Multiple Sclerosis patients. Materials & Methods: In this Quasi-experimental study, 50 Multiple Sclerosis patients wer...

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

Science.gov (United States)

Viswanathan, S.; Rose, N.; Masita, A.; Dhaliwal, J. S.; Puvanarajah, S. D.; Rafia, M. H.; Muda, S.

2013-01-01

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

Directory of Open Access Journals (Sweden)

S. Viswanathan

2013-01-01

Full Text Available Background. Multiple sclerosis (MS is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

X-irradiation of thyroid during therapy of patients with multiple sclerosis

International Nuclear Information System (INIS)

Agte, B.S.; Efimova, A.S.; Kalmykova, T.N.; Bajkova, V.P.

1985-01-01

X-radiation of 27 patients with thyroid at acute therapeutically resistant, progradient form of multiple sclerosis has been applied. Indistinct therapeutic effect attributed to depression of auto-aggressive allergic processes in cerebrospinal formations is noted in 20 patients after one or two courses of radiotherapy. The method can be used in complex therapy of progradient forms of multiple sclerosis

An observational study of alemtuzumab following fingolimod for multiple sclerosis

DEFF Research Database (Denmark)

Willis, Mark; Pearson, Owen; Illes, Zsolt

2017-01-01

OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod...... then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. RESULTS: Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39-215) months and follow-up from time of first...... consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens....

Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

International Nuclear Information System (INIS)

Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

1986-01-01

Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p<0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects. (author)

Accelerated Cure Project for Multiple Sclerosis

Science.gov (United States)

... questions and enable an era of optimized MS treatment. Read more... The Accelerated Cure Project for MS is a non-profit, 501(c)(3) tax-exempt organization whose mission is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon β-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

Science.gov (United States)

Lanzillo, R; Di Somma, C; Quarantelli, M; Carotenuto, A; Pivonello, C; Moccia, M; Cianflone, A; Marsili, A; Puorro, G; Saccà, F; Russo, C V; De Luca Picione, C; Ausiello, F; Colao, A; Brescia Morra, V

2017-02-01

Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon β (IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. © 2016 EAN.

Hopelessness, Depression and Life Satisfaction Among The Patients With Multiple Sclerosis

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Güler Duru Aşiret

2014-03-01

Full Text Available OBJECTIVE: This study was carried out to determine the level of hopelessness, depression, and life satisfaction among patients with multiple sclerosis. METHODS: 65 patients with multiple sclerosis, treated at the neurology clinic of a university hospital, were included in this study. In this descriptive study, a data collection form developed by the researchers, the Beck Depression Scale, and the Beck Hopelessness and Life Satisfaction Scale were used. RESULTS: Almost half (43.1% of the patients exhibited severe depressive symptoms. Patients’ hopelessness and life satisfaction levels were moderate. The scores on depression and life satisfaction scales were correlated negatively. While patients’ traits including female gender, low economic level, difficulties in walking, and fatigue were associated with reduced life satisfaction; variables such as having a child, low economic and education levels, experiencing incontinence, and fatigue were related to a higher level of depressive symptoms. CONCLUSION: The majority of patients were depressed; life satisfaction and hopelessness levels were moderate. Linear regression analysis revealed that education and emotional problems determined 42% of the depression score; and economic level and emotional problems identified 32% of the life satisfaction score

Infectious mononucleosis and multiple sclerosis - Updated review on associated risk.

Science.gov (United States)

Sheik-Ali, Sharaf

2017-05-01

There has been substantial evidence accumulating on the role of infectious mononucleosis (IM) and the subsequent risk of obtaining Multiple Sclerosis (MS). Up to date studies not previously explored were reviewed by the author to further clarify the association. Medline and Web of Science were searched with no time constraints for articles exploring an association between Multiple Sclerosis and Infectious Mononucleosis. 24 articles were found, totalling 1063 cases and 13,227 cohort/controls. 23/24 (96%) articles reported a significant association of Infectious Mononucleosis on the risk of subsequent multiple sclerosis. Overall, new literature on IM and risk of MS categorically supports the association. Future work should focus on other risk factors such as age and gender on IM and subsequent risk of MS. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Body fluid markers to monitor multiple sclerosis: The assays and the challenges

NARCIS (Netherlands)

Laman, J.D.; Thompson, E.J.; Kappos, L.

1998-01-01

The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis

Type 1 diabetes and multiple sclerosis

DEFF Research Database (Denmark)

Nielsen, N.M.; Westergaard, T.; Frisch, M.

2006-01-01

BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil....... OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish...

Managing treatment fatigue in patients with multiple sclerosis on long-term therapy: the role of multiple sclerosis nurses

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Crawford A

2014-08-01

Full Text Available Ann Crawford, Sally Jewell,* Holly Mara, Laura McCatty, Regina Pelfrey The Lash Group; Frisco, TX, USA *Sally Jewell is now retired Abstract: This article discusses the many ways that nurses can address the factors that lead to treatment fatigue in patients with multiple sclerosis (MS on long-term disease-modifying therapy, ultimately helping to preserve the patient’s health and quality of life. Patients with MS on long-term therapy may suffer from treatment fatigue and poor adherence due to a variety of different factors, including difficulties with injections, anxiety/depression, financial problems, and inaccurate beliefs about the MS disease process. Because MS nurses have regular interactions with patients, they are ideally situated to help patients cope with these and other factors that may limit adherence. Keywords: multiple sclerosis, disease-modifying therapy, injection, nurse

[Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain].

Science.gov (United States)

Piñol, C

2016-05-01

The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1b (IFNβ-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNβ-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNβ-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNβ-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. Early treatment with IFNβ-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Musical identity of patients with multiple sclerosis.

Science.gov (United States)

Moreira, Shirlene Vianna; França, Cecília Cavalieri; Moreira, Marcos Aurélio; Lana-Peixoto, Marco Aurélio

2009-03-01

Musical autobiographies consist of a powerful therapeutic tool by which individuals define themselves. The use of this technique may help (re)construction personal identities and improve quality of life of patients with multiple sclerosis (MS). Eight adult patients on treatment at CIEM Multiple Sclerosis Investigation Center after selecting 10 to 15 pieces of music most significant in their lives were interviewed. The data collected were classified according to Even Rudd categories, which reveal how a person expresses his personal, social, temporal and transpersonal identities. We observed that recall of musical history makes MS patients get better perception both of their feelings and body awareness, as well as provide them with an alternative way to express themselves, activate and contextualize affective memories, and achieving a sense of life continuity in spite of the disease.

[The influence of high-tone power therapy on the functional status of patients with multiple sclerosis].

Science.gov (United States)

Kubsik, Anna; Klimkiewicz, Paulina; Klimkiewicz, Robert; Jankowska, Katarzyna; Jankowska, Agnieszka; Woldańska-Okońska, Marta

2014-07-01

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, which is characterized by diverse symptomatology. Most often affects people at a young age gradually leading to their disability. Looking for new therapies to alleviate neurological deficits caused by the disease. One of the alternative methods of therapy is high - tone power therapy. The article is a comparison of high-tone power therapy and kinesis in improving patients with multiple sclerosis. The aim of this study was to evaluate the effectiveness of high-tone power therapy and exercises in kinesis on the functional status of patients with multiple sclerosis. The study involved 20 patients with multiple sclerosis, both sexes, treated at the Department of Rehabilitation and Physical Medicine in Lodz. Patients were randomly divided into two groups studied. In group high-tone power therapy applied for 60 minutes, while in group II were used exercises for kinesis. Treatment time for both groups of patients was 15 days. To assess the functional status scale was used: Expanded Disability Status Scale of Kurtzke (EDSS), as well as by Barthel ADL Index. Assessment of quality of life were made using MSQOL Questionnaire-54. For the evaluation of gait and balance using Tinetti scale, and pain VAS rated, and Laitinen. Changes in muscle tone was assessed on the basis of the Ashworth scale. Both group I and II improved on scales conducted before and after therapy. In group I, in which the applied high-tone power therapy, reported statistically significant results in 9 out of 10 tested parameters, while in group II, which was used in the exercises in kinesis an improvement in 6 out of 10 tested parameters. Correlating the results of both the test groups in relation to each other did not show statistically significant differences. High-Tone Power Therapy beneficial effect on the functional status of patients with multiple sclerosis. Obtaining results in terms of number of tested

Cognitive Impairment in Multiple Sclerosis

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Farnaz Etesam

2014-01-01

Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

Percutaneous high-frequency selective rhizotomy in the trigeminal neuralgia therapy in multiple sclerosis

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V. M. Tyurnikov

2012-01-01

Full Text Available Trigeminal neuralgia is a rare symptom of multiple sclerosis affecting the disability. Multiple sclerosis related trigeminal neuralgia has been attributed to a demyelinating lesion in the pons. When the adequate pain drug-relieve therapy is not possible or when the patient becomes refractory to the treatment or can not continue pharmacological treatment because of the side effects, surgical intervention, including percutaneous radiofrequency rhizotomy is being discussed. Literature review and the data upon the efficiency and safety of this neurosurgical treatment in 16 patients with multiple sclerosis have been analyzed. Percutaneous radiofrequency rhizotomy has been proved to be a safe, reproducible and effective method of the symptomatic surgical treatment of trigeminal neuralgia in patients with multiple sclerosis in cases of the intolerance/inefficiency of the pharmacological therapy.

Effects of education level and employment status on HRQoL in early relapsing-remitting multiple sclerosis.

Science.gov (United States)

Patti, F; Pozzilli, C; Montanari, E; Pappalardo, A; Piazza, L; Levi, A; Onesti, E; Pesci, I

2007-07-01

To evaluate the effects of education level and employment status on health-related quality of life (HRQoL) in a large cohort of patients affected by relapsing-remitting multiple sclerosis (RRMS). Patients This study included 648 patients with RRMS attending 40 Italian MS centers. Inclusion criteria were an Expanded Disability Status Scale (EDSS) score between 1.0 and 5.5; stable disease on enrollment; and no previous treatment with interferons, glatiramer acetate, or immunosuppressive drugs. Quality of life (QoL) was evaluated by the Multiple Sclerosis Quality of Life-54 questionnaire (MSQoL-54). Employed patients scored significantly higher than other patient groups in the majority of MSQoL-54 domains. Similarly, patients with academic degrees and secondary education had higher scores than those with primary education (ie, eight years of education) in several domains of HRQoL. Patients who were employed with a high educational level achieved significantly better scores than unemployed patients with a lower educational level. In multivariate analysis, occupation and educational level were found to be significant and independent predictors of HRQoL. The results of our study suggest the importance of sustaining employment after a recent diagnosis of MS. In addition, education has a great influence on HRQoL; a higher education level may determine a stronger awareness of the disease, and a better ability to cope with the challenges of a chronic disease such as MS.

Antigen-specific therapies in multiple sclerosis

NARCIS (Netherlands)

Noort, J.M. van

1998-01-01

Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is

Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment

NARCIS (Netherlands)

Visser, Leo H.; Heerings, Marco A.; Jongen, Peter J.; van der Hiele, Karin

2016-01-01

Background: The adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study

Physical Telerehabilitation in Patients with Multiple Sclerosis with Significant Mobility Impairment

Science.gov (United States)

2017-10-01

Award Number: W81XWH-16-1-0704 TITLE: Physical Telerehabilitation in Patients with Multiple Sclerosis with Significant Mobility Impairment...including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing ...29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Physical Telerehabilitation in Patients with Multiple Sclerosis with Significant Mobility

Comparison of Masking Level Difference in Patients with Multiple Sclerosis and Healthy Control Group

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Soghrat Faghihzadeh

2012-03-01

Full Text Available Background and Aim: Multiple sclerosis (MS is a neurological disorder that involves central nervous system. Studies have showed that multiple sclerosis affects behavioral central auditory tests, such as masking release or masking level difference (MLD. The purpose of this study is to compare the masking level difference between multiple sclerosis patients and normal subjects.Methods: This cross sectional and non-interventional study was conducted on 32 multiple sclerosis patients aged between 20-50 years and 32 controls matched for age and gender in Faculty of Rehabilitation, Tehran University of Medical Sciences. masking level difference test was performed on each subject.Results: The mean masking level difference in the two groups was significantly different (p<0.01 however, gender did not prove to play a role in this difference.Conclusion: As part of the multiple sclerosis diagnosis panel, masking level difference test is an efficient modality for evaluation of hearing impairment and monitoring of rehabilitation progress.

Multiple sclerosis and birth order.

OpenAIRE

James, W H

1984-01-01

Studies on the birth order of patients with multiple sclerosis have yielded contradictory conclusions. Most of the sets of data, however, have been tested by biased tests. Data that have been submitted to unbiased tests seem to suggest that cases are more likely to occur in early birth ranks. This should be tested on further samples and some comments are offered on how this should be done.

Multiple Sclerosis in Older Adults: The Clinical Profile and Impact of Interferon Beta Treatment

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Afsaneh Shirani

2015-01-01

Full Text Available Background. We examined (1 patient characteristics and disease-modifying drug (DMD exposure in late-onset (LOMS, ≥50 years at symptom onset versus adult-onset (AOMS, 18–<50 years MS and (2 the association between interferon-beta (IFNβ and disability progression in older relapsing-onset MS adults (≥50 years. Methods. This retrospective study (1980–2004, British Columbia, Canada included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90 were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses. Results. LOMS patients (6% were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18–1.22 or historical controls (HR: 0.54; 95% CI: 0.20–1.42 were considered. Conclusion. LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients.

Sexual habits before multiple sclerosis: a national case-control study

DEFF Research Database (Denmark)

Lidegaard, O.; Svendsen, Anne Louise; Lidegaard, Øjvind

2008-01-01

The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease.......The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease....

Defining the clinical course of multiple sclerosis

DEFF Research Database (Denmark)

Lublin, Fred D; Reingold, Stephen C; Cohen, Jeffrey A

2014-01-01

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts...

Coping strategies and mood profiles in patients with multiple sclerosis

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Aysel Milanlioglu

2014-07-01

Full Text Available Objective: The aim of the present study was to investigate the coping strategies, mood characteristics and the association between these aspects in patients diagnosed with multiple sclerosis and healthy subjects. Method: Fifty consecutive patients who were diagnosed with multiple sclerosis according to McDonald criteria and thirty-one healthy subjects were included in the study. In addition to the sociodemographic form, Expanded Disability Status Scale (EDSS, Coping Orientation for Problem Experiences Scale (COPE, and Profile of Mood States (POMS tests were applied to the participants. Results: Non-functional coping strategies were significantly higher in the secondary-progressive type (p≤0.05. Depression-dejection, fatigue-inertia and total POMS scores were significantly higher in the secondary-progressive type (p≤0.05. Conclusion: The results of our study demonstrate the importance of rehabilitation programs that encourage exercise among patients with multiple sclerosis to increase vigor-activity levels.

Utilization of dimethyl fumarate and related molecules for treatment of multiple sclerosis, cancer, and other diseases

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Azzam Maghazachi

2016-07-01

Full Text Available Several drugs have been approved for treatment of multiple sclerosis. Dimethyl fumarate (DMF is utilized as an oral drug to treat this disease and is proven to be potent with less side effects than several other drugs. On the other hand, monomethyl fumarate (MMF, a related compound has not been examined in greater details although it has the potential as a therapeutic drug for multiple sclerosis and other diseases. The mechanism of action of DMF or MMF is related to their ability to enhance the antioxidant pathways and to inhibit reactive oxygen species. However, other mechanisms have also been described which include effects on monocytes, dendritic cells, T cells, and natural killer cells. It is also reported that DMF might be useful for treating psoriasis, asthma, aggressive breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. In this article we will touch on some of these diseases with an emphasis on the effects of DMF and MMF on various immune cells.

'Normal' and 'failing' mothers: Women's constructions of maternal subjectivity while living with multiple sclerosis.

Science.gov (United States)

Parton, Chloe; Katz, Terri; Ussher, Jane M

2017-10-01

Multiple sclerosis causes physical and cognitive impairment that can impact women's experiences of motherhood. This study examined how women construct their maternal subjectivities, or sense of self as a mother, drawing on a framework of biographical disruption. A total of 20 mothers with a multiple sclerosis diagnosis took part in semi-structured interviews. Transcripts were analysed using thematic decomposition to identify subject positions that women adopted in relation to cultural discourses of gender, motherhood and illness. Three main subject positions were identified: 'The Failing Mother', 'Fear of Judgement and Burdening Others' and 'The Normal Mother'. Women's sense of self as the 'Failing Mother' was attributed to the impact of multiple sclerosis, contributing to biographical disruption and reinforced through 'Fear of Judgement and Burdening Others' within social interactions. In accounts of the 'Normal Mother', maternal subjectivity was renegotiated by adopting strategies to manage the limitations of multiple sclerosis on mothering practice. This allowed women to self-position as 'good' mothers. Health professionals can assist women by acknowledging the embodied impact of multiple sclerosis on maternal subjectivities, coping strategies that women employ to address potential biographical disruption, and the cultural context of mothering, which contributes to women's experience of subjectivity and well-being when living with multiple sclerosis.

Relationship Between Spiritual Well-Being and Self-Management Among Iranian People With Multiple Sclerosis

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Zarei

2015-10-01

Full Text Available Background Self-management is the cornerstone for controlling multiple sclerosis. As one’s sense of meaning in life and his/her relationship with a higher power, spiritual well-being is an important coping resource in some chronic diseases. However, little is known about the role of spiritual well-being in self-management of people diagnosed with multiple sclerosis. Objectives This study was aimed to assess the relationship between spiritual well-being and self-management among Iranian people with multiple sclerosis. Patients and Methods Two hundred ninety-one people diagnosed with multiple sclerosis belonging to the Multiple Sclerosis Society of Mashhad, Iran, participated in this cross-sectional analytical study conducted in 2014. Demographic information was collected by using a demographic form. The multiple sclerosis self-management scale-revised (2011, developed by Bishop and Frain, was used to evaluate self-management of multiple sclerosis symptoms. Spiritual well-being of participants was assessed by using the spiritual well-being questionnaire developed by Paloutzian and Ellison in 1983. Descriptive statistic and inferential statistical methods including Pearson and Spearman’s coefficient, stepwise multiple regression, independent t-test, Mann-Whitney U test, one-way ANOVA, and Kruskal-Wallis test were employed by using SPSS, version 16.0. The significance level was set at P ≤ 0.05. Results Overall, the participants reported moderate levels of self-management and spiritual well-being as recorded on the multiple sclerosis self-management scale-revised and the spiritual well-being questionnaire. There was a significant correlation between the participants’ spiritual well-being and self-management scores (r = 0.59, P < 0.001. Furthermore, participants’ self-management was significantly correlated with existential health (r = 0.52, P < 0.001 and religious health (r = 0.57, P < 0.001. Finally, 40% of the variance of self