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Sample records for relapsing-remitting multiple sclerosis

  1. Cognitive impairment in relapsing remitting Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Saška Roškar

    2003-06-01

    Full Text Available The purpose of the study was to identify changes in cognitive abilities that affect patients with relapsing remitting form of multiple sclerosis (MS and to find out which instrument manifests them best. The performance of MS patients was compared to a matched group of healthy people using three neuropsychological tests: Wisconsin card sorting test (WCST, Stroop color and word test and Trail making test (TMT part B. Results on all three tests indicate general cognitive impairments in the group of patients. Compared to the group of healthy people patients with MS exhibited impaired ability of abstract reasoning (WCST, impaired cognitive flexibility and less resistance to irrelevant stimuli (Stroop color and word test, slowed information processing and impaired ability of shifting attention from one symbol to another (TMT. The largest differences between groups occured in Stroop color and word test as well as in TMT. The estimation of cognitive abilities of MS patients is of high importance and sistematicaly observing of changes in those abilities should be considered.

  2. Cladribine tablets for relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Rammohan, Kottil; Giovannoni, Gavin; Comi, Giancarlo

    2012-01-01

    BACKGROUND: In the phase III CLARITY study, treatment with cladribine tablets at cumulative doses of 3.5 or 5.25mg/kg over 96 weeks led to significant reductions in annualized relapse rates (ARR) versus placebo in patients with relapsing-remitting multiple sclerosis. Further post hoc analyses...... of CLARITY study data were conducted to determine the efficacy of cladribine tablets across patient subgroups stratified by baseline characteristics. METHODS: Relapse rates over the 96-week CLARITY study were analyzed in cohorts stratified by demographics; disease duration; treatment history and disease...... activity at baseline. RESULTS: In the intent-to-treat population (n=437, 433 and 456 in the placebo, cladribine 3.5 and 5.25mg/kg groups, respectively), treatment with cladribine tablets 3.5 and 5.25mg/kg led to consistent improvements in ARR versus placebo in patients stratified by gender; age (≤40...

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

    DEFF Research Database (Denmark)

    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....

  4. Daclizumab for the treatment of relapsing-remitting multiple sclerosis.

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    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.

  5. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

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    Genaro Gabriel Ortiz

    2009-01-01

    Full Text Available Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old and 7 men (5 aged from 20 to 30 and 2 were > 40 years old fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites, lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals, and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress.

  6. 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)

  7. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

  8. Secondary Progressive and Relapsing Remitting Multiple Sclerosis Leads to Motor-Related Decreased Anatomical Connectivity

    DEFF Research Database (Denmark)

    Lyksborg, Mark; Siebner, Hartwig R.; Sørensen, Per S.

    2014-01-01

    Multiple sclerosis (MS) damages central white matter pathways which has considerable impact on disease-related disability. To identify disease-related alterations in anatomical connectivity, 34 patients (19 with relapsing remitting MS (RR-MS), 15 with secondary progressive MS (SP-MS) and 20 healthy...

  9. Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients

    OpenAIRE

    Messinis, L.; Kosmidis, M. H.; Vlahou, C.; Malegiannaki, A. C.; Gatzounis, G.; Dimisianos, N.; Karra, A.; Kiosseoglou, G.; Gourzis, P.; Papathanasopoulos, P.

    2013-01-01

    The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensi...

  10. 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.

  11. Different cognitive profiles of Brazilian patients with relapsing-remitting and primary progressive multiple sclerosis

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    Dóra-Neide Rodrigues

    2011-08-01

    Full Text Available Cognitive impairment is a symptom of multiple sclerosis (MS. Different clinical forms of multiple sclerosis have different cognitive profiles, according to findings of previous studies which used extensive batteries of neuropsychological tests. OBJECTIVE: To investigate cognitive profiles of Brazilian patients with relapsing-remitting multiple sclerosis (RRMS and primary progressive multiple sclerosis (PPMS by using a brief battery of neuropsychological tests. METHOD: Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired with healthy control subjects, regarding gender, age, and education level. RESULTS: On Symbol Digit Modalities Test and Hooper Visual Organization Test, cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and in 69% of primary progressive. CONCLUSION: Cognitive profiles of relapsing-remitting and primary progressive patients are different

  12. Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

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    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

  13. The innovative development in interferon beta treatments of relapsing-remitting multiple sclerosis

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    Madsen, Claus

    2017-01-01

    The introduction of interferon beta therapies more than 20 years ago marked a milestone in the treatment of relapsing-remitting multiple sclerosis (RRMS) with a significant impact on the approach to modern multiple sclerosis (MS) care. Key learnings and perspectives from the early days of disease...... modifying therapies in MS have improved the knowledge base of MS, need for treatment, and patient care. The continuous development of interferons over the past two decades outlines a journey with increased understanding of the pharmacodynamics and pharmacokinetic mechanisms of interferons, leading...

  14. Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

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    Julio Sotelo

    2011-01-01

    Full Text Available Multiple sclerosis (MS is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS.

  15. Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

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    Sotelo, Julio; Corona, Teresa

    2011-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID:22096629

  16. [Neuropsychology of mildly disabled patients with relapsing-remitting multiple sclerosis].

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    Santiago Rolanía, Olga; Guàrdia Olmos, Joan; Arbizu Urdiain, Txomin

    2006-02-01

    Previous papers have mainly demonstrated the presence of cognitive impairment in patients with multiple sclerosis (MS), these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to 216 relapsing-remitting MS patients with mild clinical disability (EDSSreproduction visual memory; and long term verbal memory of texts, and information processing speed. We also observed greeter incidence of depressive symptoms in patients. And a little relation of the cognitive deficits with the clinical variables in these phase of the disease.

  17. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per S; Lisby, Steen; Grove, Richard

    2014-01-01

    OBJECTIVES: We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple sclerosis (RRMS). METHODS: In this randomized, double-blind, placebo-controlled study, patients received 2 ofatumumab infusions (100 mg, 300 mg......, or 700 mg) or placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety and efficacy were assessed. RESULTS: Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients in the 300-mg group...

  18. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

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    Karin van der Hiele

    Full Text Available The majority of patients with Multiple Sclerosis (MS are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed. Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53=2.76, p=0.008 and reported more organising and planning problems (χ2(1=6.3, p=0.012, higher distractibility (Kendall's tau-b= -0.24, p=0.03 and more cognitive fatigue (U=205.0, p=0.028, r=-0.30 than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28. Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

  19. Work Participation and Executive Abilities in Patients with Relapsing-Remitting Multiple Sclerosis.

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    van der Hiele, Karin; van Gorp, Dennis; Ruimschotel, Rob; Kamminga, Noëlle; Visser, Leo; Middelkoop, Huub

    2015-01-01

    The majority of patients with Multiple Sclerosis (MS) are unable to retain employment within 10 years from disease onset. Executive abilities, such as planning, working memory, attention, problem solving, inhibition and mental flexibility may have a direct impact on the ability to maintain a job. This study investigated differences in subjective and objective executive abilities between relapsing-remitting MS patients with and without a paid job. We included 55 relapsing-remitting MS patients from a community-based sample (47 females; mean age: 47 years; 36% employed). Patients underwent neurological, cognitive and psychological assessments at their homes, including an extensive executive test battery. We found that unemployed patients had a longer disease duration (t(53)=2.76, p=0.008) and reported more organising and planning problems (χ2(1)=6.3, p=0.012), higher distractibility (Kendall's tau-b= -0.24, p=0.03) and more cognitive fatigue (U=205.0, p=0.028, r=-0.30) than employed patients. Unemployed patients completed slightly less categories on the Wisconsin Card Sorting Test (U=243.5, p=0.042, r=-0.28). Possible influential factors such as age, educational level, physical functioning, depression and anxiety did not differ between groups. In conclusion, while relapsing-remitting MS patients without a paid job reported more executive problems and cognitive fatigue than patients with a paid job, little differences were found in objective executive abilities. Further research is needed to examine possible causal relations.

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

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    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.

  1. 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.

  2. Use of fingolimod in patients with relapsing remitting multiple sclerosis in Kuwait.

    Science.gov (United States)

    Alroughani, R; Ahmed, S F; Behbehani, R; Al-Hashel, J

    2014-04-01

    Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety. To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait. We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions). 76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1). Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. 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.

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

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    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.

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

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    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

  6. Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study

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    Rocco Totaro

    2015-01-01

    Full Text Available Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months. The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

  7. Phonological fluency strategy of switching differentiates relapsing-remitting and secondary progressive multiple sclerosis patients.

    Science.gov (United States)

    Messinis, L; Kosmidis, M H; Vlahou, C; Malegiannaki, A C; Gatzounis, G; Dimisianos, N; Karra, A; Kiosseoglou, G; Gourzis, P; Papathanasopoulos, P

    2013-01-01

    The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.

  8. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

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    Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

    2011-06-01

    Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

  9. Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

    2017-07-01

    The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

  10. Histogram analysis of diffusion measures in clinically isolated syndromes and relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Yu Chunshui; Lin Fuchun; Liu Yaou; Duan Yunyun; Lei Hao; Li Kuncheng

    2008-01-01

    Objective: The purposes of our study were to employ diffusion tensor imaging (DTI)-based histogram analysis to determine the presence of occult damage in clinically isolated syndrome (CIS), to compare its severity with relapsing-remitting multiple sclerosis (RRMS), and to determine correlations between DTI histogram measures and clinical and MRI indices in these two diseases. Materials and methods: DTI scans were performed in 19 CIS and 19 RRMS patients and 19 matched healthy volunteers. Histogram analyses of mean diffusivity and fractional anisotropy were performed in normal-appearing brain tissue (NABT), normal-appearing white matter (NAWM) and gray matter (NAGM). Correlations were analyzed between these measures and expanded disability status scale (EDSS) scores, T 2 WI lesion volumes (LV) and normalized brain tissue volumes (NBTV) in CIS and RRMS patients. Results: Significant differences were found among CIS, RRMS and control groups in the NBTV and most of the DTI histogram measures of the NABT, NAWM and NAGM. In CIS patients, some DTI histogram measures showed significant correlations with LV and NBTV, but none of them with EDSS. In RRMS patients, however, some DTI histogram measures were significantly correlated with LV, NBTV and EDSS. Conclusion: Occult damage occurs in both NAGM and NAWM in CIS, but the severity is milder than that in RRMS. In CIS and RRMS, the occult damage might be related to both T2 lesion load and brain tissue atrophy. Some DTI histogram measures might be useful for assessing the disease progression in RRMS patients

  11. Wechsler Adult Intelligence Scale-Fourth Edition performance in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Ryan, Joseph J; Gontkovsky, Samuel T; Kreiner, David S; Tree, Heather A

    2012-01-01

    Forty patients with relapsing-remitting multiple sclerosis (MS) completed the 10 core Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests. Means for age and education were 42.05 years (SD = 9.94) and 14.33 years (SD = 2.40). For all participants, the native language was English. The mean duration of MS diagnosis was 8.17 years (SD = 7.75), and the mean Expanded Disability Status Scale (EDSS; Kurtzke, 1983 ) score was 3.73 (SD = 1.41) with a range from 2.0 to 6.5. A control group of healthy individuals with similar demographic characteristics also completed the WAIS-IV and were provided by the test publisher. Compared to controls, patients with MS earned significantly lower subtest and composite scores. The patients' mean scores were consistently in the low-average to average range, and the patterns of performance across groups did not differ significantly, although there was a trend towards higher scores on the Verbal Comprehension Index (VCI) and lower scores on the Processing Speed Index (PSI). Approximately 78% of patients had actual Full Scale IQs that were significantly lower than preillness, demographically based IQ estimates.

  12. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin [Shandong University, Shandong Medical Imaging Research Institute, Jinan (China); Edden, Richard A.E. [The Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Kennedy Krieger Institute, FM Kirby Center for Functional Brain Imaging, Baltimore, MD (United States); Li, Hao [Air Force General Hospital PLA, Beijing (China); Chen, Weibo [Philips Healthcare, Shanghai (China); Liu, Xiaohui [Shandong Provincial Hospital Affiliated to Shandong University, Department of Neurology, Jinan (China)

    2018-03-15

    To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

  13. Reduced GABA levels correlate with cognitive impairment in patients with relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Cao, Guanmei; Gao, Fei; Gong, Tao; Wang, Guangbin; Zhao, Bin; Edden, Richard A.E.; Li, Hao; Chen, Weibo; Liu, Xiaohui

    2018-01-01

    To investigate if brain gamma-aminobutyric acid (GABA) levels in patients with relapsing-remitting multiple sclerosis (RRMS) are abnormal compared with healthy controls, and their relationship to cognitive function in RRMS. Twenty-eight RRMS patients and twenty-six healthy controls underwent magnetic resonance spectroscopy (MRS) at 3-T to detect GABA signals from posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC) and left hippocampus using the 'MEGAPoint Resolved Spectroscopy Sequence' (MEGA-PRESS) technique. All subjects also underwent a cognitive assessment. In RRMS patients, GABA+ were lower in the PCC (p = 0.036) and left hippocampus (p = 0.039) compared with controls, decreased GABA+ in the PCC and left hippocampus were associated with specific cognitive functions (r = -0.452, p = 0.016 and r = 0.451, p = 0.016 respectively); GABA+ in the mPFC were not significantly decreased or related to any cognitive scores (p > 0.05). This study demonstrates that abnormalities of the GABAergic system may be present in the pathogenesis of RRMS and suggests a potential link between regional GABA levels and cognitive impairment in patients with RRMS. (orig.)

  14. Quantitative diffusion tensor deterministic and probabilistic fiber tractography in relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Hu Bing; Ye Binbin; Yang Yang; Zhu Kangshun; Kang Zhuang; Kuang Sichi; Luo Lin; Shan Hong

    2011-01-01

    Purpose: Our aim was to study the quantitative fiber tractography variations and patterns in patients with relapsing-remitting multiple sclerosis (RRMS) and to assess the correlation between quantitative fiber tractography and Expanded Disability Status Scale (EDSS). Material and methods: Twenty-eight patients with RRMS and 28 age-matched healthy volunteers underwent a diffusion tensor MR imaging study. Quantitative deterministic and probabilistic fiber tractography were generated in all subjects. And mean numbers of tracked lines and fiber density were counted. Paired-samples t tests were used to compare tracked lines and fiber density in RRMS patients with those in controls. Bivariate linear regression model was used to determine the relationship between quantitative fiber tractography and EDSS in RRMS. Results: Both deterministic and probabilistic tractography's tracked lines and fiber density in RRMS patients were less than those in controls (P < .001). Both deterministic and probabilistic tractography's tracked lines and fiber density were found negative correlations with EDSS in RRMS (P < .001). The fiber tract disruptions and reductions in RRMS were directly visualized on fiber tractography. Conclusion: Changes of white matter tracts can be detected by quantitative diffusion tensor fiber tractography, and correlate with clinical impairment in RRMS.

  15. Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

    Science.gov (United States)

    Escribano, Begona M; Aguilar-Luque, Macarena; Bahamonde, Carmen; Conde, Cristina; Lillo, Rafael; Sanchez-Lopez, Fernando; Giraldo, Ana I; Cruz, Antonio H; Luque, Evelio; Gascon, Felix; Aguera, Eduardo; Tunez, Isaac

    2016-01-01

    The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

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

    DEFF Research Database (Denmark)

    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....

  17. Improvement of driving skills in persons with relapsing-remitting multiple sclerosis: a pilot study.

    Science.gov (United States)

    Akinwuntan, Abiodun Emmanuel; Devos, Hannes; Baker, Kelly; Phillips, Kendra; Kumar, Vibha; Smith, Suzanne; Williams, Mitzi Joi

    2014-03-01

    To determine the potential to improve driving-related skills using a simulator-based program in persons with relapsing-remitting multiple sclerosis (RRMS). Pre-post intervention. A university driving simulator laboratory. Participants (N=50) with RRMS and Expanded Disability Status Scale (EDSS) scores between 1 and 7 were enrolled. Pre- and posttraining data from 36 participants (mean age ± SD, 46±11y; 30 women) who received training and 6 participants (mean age ± SD, 48±13y; 5 women) who did not receive training (control group) were compared. Five hours of driving training in a simulator. Performance on a road test at pre- and posttraining. Secondary outcome measures were performance on visual, physical, and cognitive tests. Overall, no significant differences were observed between the training and control groups before and after training. However, 4 of the 7 participants in the training group who failed the road test at pretraining passed posttraining, while the only participant in the control group who failed at pretraining still failed at posttraining. The training group also improved on perception of red and colored numbers, the Paced Auditory Serial Addition Test, and the dot cancellation test of the Stroke Driver Screening Assessment battery and reported less fatigue. These improvements were most pronounced among those with an EDSS score between 3 and 7. This pilot study demonstrates the potential of using a simulator to improve driving-related visual, cognitive, and on-road skills in individuals with RRMS, particularly those with an EDSS score >3. Future randomized controlled trials with adequate power are needed to expand this field of study. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  18. Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

    Science.gov (United States)

    Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

    2009-06-01

    We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

  19. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

    Science.gov (United States)

    Kalincik, Tomas; Brown, J William L; Robertson, Neil; Willis, Mark; Scolding, Neil; Rice, Claire M; Wilkins, Alastair; Pearson, Owen; Ziemssen, Tjalf; Hutchinson, Michael; McGuigan, Christopher; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Grammond, Pierre; Alroughani, Raed; Pucci, Eugenio; Sola, Patrizia; Hupperts, Raymond; Lechner-Scott, Jeannette; Terzi, Murat; Van Pesch, Vincent; Rozsa, Csilla; Grand'Maison, François; Boz, Cavit; Granella, Franco; Slee, Mark; Spitaleri, Daniele; Olascoaga, Javier; Bergamaschi, Roberto; Verheul, Freek; Vucic, Steve; McCombe, Pamela; Hodgkinson, Suzanne; Sanchez-Menoyo, Jose Luis; Ampapa, Radek; Simo, Magdolna; Csepany, Tunde; Ramo, Cristina; Cristiano, Edgardo; Barnett, Michael; Butzkueven, Helmut; Coles, Alasdair

    2017-04-01

    Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], pmultiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly

  20. "Always looking for a new balance": toward an understanding of what it takes to continue working while being diagnosed with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Meide, Hanneke van der; Gorp, Dennis van; van der Hiele, Karin; Visser, Leo

    2017-06-22

    The aim of this study was to gain insight into the meaning of work in the everyday lives of people with relapsing-remitting multiple sclerosis, and the barriers and facilitators to staying in work. Nineteen employed adults diagnosed with relapsing-remitting multiple sclerosis participated in narrative interviews. All interviews were transcribed and coded for thematic analysis. For people with relapsing-remitting multiple sclerosis, continuing to work was a precarious balancing act. Five themes influenced this balance: becoming familiar with the disease, adjusting expectations, having an understanding and realistic line manager, seeing work as meaningful life activity and strategic considerations. People receiving a diagnosis of relapsing-remitting multiple sclerosis have to refamiliarize themselves with their own body in a meaningful way to be able to continue their work. Rehabilitation professionals can support them herein by taking into account not merely functional capabilities but also identity aspects of the body. Medication that stabilizes symptoms supports making the necessary adjustments. A trusting relationship with the line manager is vital for this adaptation process. Additionally, a match between being adequately challenged by work, while still having the capacity to meet those work demands, is needed, as is long-term financial stability. Implications for rehabilitation Rehabilitation professionals can support employees with relapsing-remitting multiple sclerosis by taking into account not merely functional capabilities but also identity aspects of the body. A trusting relationship with the line manager, including a timely disclosure of the diagnosis, is vital for people with relapsing-remitting multiple sclerosis to remain at work. For people with relapsing-remitting multiple sclerosis, there is a delicate balance between being adequately challenged by work while still having the capacity to meet work demands.

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

    Science.gov (United States)

    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.

  2. MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Zivadinov, R.; De Masi, R.; Nasuelli, D.; Monti Bragadin, L.; Cazzato, G.; Zorzon, M.; Ukmar, M.; Pozzi-Mucelli, R.S.; Grop, A.

    2001-01-01

    Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores ≤ 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8 %) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease. (orig.)

  3. Azathioprine versus Beta Interferons for Relapsing-Remitting Multiple Sclerosis: A Multicentre Randomized Non-Inferiority Trial

    Science.gov (United States)

    Massacesi, Luca; Tramacere, Irene; Amoroso, Salvatore; Battaglia, Mario A.; Benedetti, Maria Donata; Filippini, Graziella; La Mantia, Loredana; Repice, Anna; Solari, Alessandra; Tedeschi, Gioacchino; Milanese, Clara

    2014-01-01

    For almost three decades in many countries azathioprine has been used to treat relapsing-remitting multiple sclerosis. However its efficacy was usually considered marginal and following approval of β interferons for this indication it was no longer recommended as first line treatment, even if presently no conclusive direct β interferon-azathioprine comparison exists. To compare azathioprine efficacy versus the currently available β interferons in relapsing-remitting multiple sclerosis, a multicenter, randomized, controlled, single-blinded, non-inferiority trial was conducted in 30 Italian multiple sclerosis centers. Eligible patients (relapsing-remitting course; ≥2 relapses in the last 2 years) were randomly assigned to azathioprine or β interferons. The primary outcome was annualized relapse rate ratio (RR) over 2 years. Key secondary outcome was number of new brain MRI lesions. Patients (n = 150) were randomized in 2 groups (77 azathioprine, 73 β interferons). At 2 years, clinical evaluation was completed in 127 patients (62 azathioprine, 65 β interferons). Annualized relapse rate was 0.26 (95% Confidence Interval, CI, 0.19–0.37) in the azathioprine and 0.39 (95% CI 0.30–0.51) in the interferon group. Non-inferiority analysis showed that azathioprine was at least as effective as β interferons (relapse RRAZA/IFN 0.67, one-sided 95% CI 0.96; p<0.01). MRI outcomes were analyzed in 97 patients (50 azathioprine and 47 β interferons). Annualized new T2 lesion rate was 0.76 (95% CI 0.61–0.95) in the azathioprine and 0.69 (95% CI 0.54–0.88) in the interferon group. Treatment discontinuations due to adverse events were higher (20.3% vs. 7.8%, p = 0.03) in the azathioprine than in the interferon group, and concentrated within the first months of treatment, whereas in the interferon group discontinuations occurred mainly during the second year. The results of this study indicate that efficacy of azathioprine is not inferior to that of

  4. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

    OpenAIRE

    Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

    2015-01-01

    We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on bra...

  5. Experience of Glatiramer Acetate in the Treatment of Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Özlem Taşkapılıoğlu

    2012-03-01

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

  6. Risk-benefit considerations in the treatment of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lugaresi A

    2013-06-01

    Full Text Available Alessandra Lugaresi,1 Maria di Ioia,1 Daniela Travaglini,1 Erika Pietrolongo,1 Eugenio Pucci,2 Marco Onofrj11Department of Neuroscience and Imaging, University “G d’Annunzio”, Chieti, 2Operative Unit Neurologia ASUR Marche Area Vasta 3, Macerata, ItalyAbstract: Multiple sclerosis (MS is a chronic demyelinating disease of the central nervous system and mainly affects young adults. Its natural history has changed in recent years with the advent of disease-modifying drugs, which have been available since the early 1990s. The increasing number of first-line and second-line treatment options, together with the variable course of the disease and patient lifestyles and expectations, makes the therapeutic decision a real challenge. The aim of this review is to give a comprehensive overview of the main present and some future drugs for relapsing-remitting MS, including risk-benefit considerations, to enable readers to draw their own conclusions regarding the risk-benefit assessment of personalized treatment strategies, taking into account not only treatment-related but also disease-related risks. We performed a Medline literature search to identify studies on the treatment of MS with risk stratification and risk-benefit considerations. We focused our attention on studies of disease-modifying, immunomodulating, and immunosuppressive drugs, including monoclonal antibodies. Here we offer personal considerations, stemming from long-term experience in the treatment of MS and thorough discussions with other neurologists closely involved in the care of patients with the disease. MS specialists need to know not only the specific risks and benefits of single drugs, but also about drug interactions, either in simultaneous or serial combination therapy, and patient comorbidities, preferences, and fears. This has to be put into perspective, considering also the risks of untreated disease in patients with different clinical and radiological characteristics

  7. Oral available agents in the treatment of relapsing remitting multiple sclerosis an overview of merits and culprits

    Directory of Open Access Journals (Sweden)

    Thöne J

    2013-02-01

    Full Text Available Jan Thöne, Gisa Ellrichmann Department of Neurology, St Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany Abstract: Multiple sclerosis (MS is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles. Keywords: cladribine, fingolimod (FTY, fumaric acid esters (BG-12, laquinimod, teriflunomide

  8. Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy

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    Foronda Jesus

    2004-06-01

    Full Text Available Abstract Background What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. Methods Thirty one patients (9 male and 22 female with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0–5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. Results A statistically significant correlation was found (r = -0.38 p Conclusions There is correlation between disability (measured by Expanded Disability Scale Score and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor.

  9. Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis

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    Guilherme Sciascia do Olival

    2013-08-01

    Full Text Available This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10% patients presented with new attacks. In addition to these patients, 2 (5% patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

  10. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

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    Georgios Koutsis

    2015-01-01

    Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  11. Relapsing remitting multiple sclerosis in x-linked charcot-marie-tooth disease with central nervous system involvement.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Floroskoufi, Paraskewi; Raftopoulou, Maria; Panas, Marios

    2015-01-01

    We report a patient with relapsing remitting multiple sclerosis (MS) and X-linked Charcot-Marie-Tooth disease (CMTX), carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr) which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS) involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars). Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  12. 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

  13. 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

  14. Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study

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    Nasim Tabrizi

    2012-01-01

    Full Text Available Background: The efficacy of mitoxantrone induction therapy in rapidly worsening multiple sclerosis (MS is well established. Plasma exchange is also applied as an adjuvant in exacerbations of relapsing MS. The aim of this study was to compare the efficacy of combination therapy with mitoxantrone and plasma exchange versus mitoxantrone alone in patients with aggressive MS. Materials and Methods: Forty patients with aggressive relapsing remitting MS were randomly put into two groups. The first group underwent monthly plasma exchange for three successive months, followed by 12 mg/m 2 mitoxantrone at the end of each course and two more doses of 6 mg/m 2 mitoxantrone in 3-month intervals. The second group received the same doses of mitoxantrone only without plasma exchange. At the end of 8 months treatment course, clinical reassessment and neuroimaging was performed and treatment was continued with interferon-β. Results: At the end of induction therapy, Expanded Disability Status Scale score was significantly improved in both groups (P < 0.001. Number of demyelinating and gadolinium-enhancing plaques in brain magnetic resonance imaging (MRI was prominently reduced in group 2 (P ≤ 0.05, but the changes were not statistically significant in group 1, except for juxtacortical plaques. Conclusion: Administration of mitoxantrone as an induction therapy in patients of aggressive relapsing remitting MS results in significant improvement of their clinical state and MRI activity. However, combination of plasma exchange with mitoxantrone gives no more benefits than mitoxantrone alone and sometimes worsens the situation possibly by reduction of mitoxantrone efficacy as a result of plasma exchange.

  15. Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

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    Gabriel Bsteh

    Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

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

    DEFF Research Database (Denmark)

    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 ...

  17. 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.

  18. The outbreak fingolimod cardiovascular side effects in relapsing-remitting multiple sclerosis patient: A longitudinal study in an Iranian population

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    Morteza Abdar

    2017-03-01

    Full Text Available BACKGROUND: Fingolimod (FTY-720 has shown efficacy in relapsing multiple sclerosis (MS, while some side effects of this drug have been recognized that the most important is cardiovascular side effects. The aim of this study was to evaluate the cardiovascular side effects of FTY-720. However, the effect of fingolimod on cardiac has not been well recognized. This study was designed to evaluate the cardiovascular side effects of fingolimod in relapsing-remitting multiple sclerosis (RRMS patient in an Iranian population. METHODS: This prospective clinical trial study was performed on 200 RRMS patients. The patients received a single daily oral dose of fingolimod 0.5 mg. During the first 6 hours after the first fingolimod dose, the patients’ vital signs and electrocardiographic traces were continuously monitored. Moreover, the patients followed up over 6 months after receiving fingolimod. RESULTS: The results showed that pulse rate (P < 0.001, systolic blood pressure (BP (P < 0.001, and diastolic BP (P < 0.001 were decreased significantly during 6 hours after receiving the first dose of fingolimod. The most reduction in vital sign was observed in 3 hours. Arrhythmia, bradycardia, and dizziness were the other complications of fingolimod, which were detected in our study. CONCLUSION: All the side effects such as hypotension and bradycardia were happened in first 3 hours after receiving the fingolimod. Indeed, we advise clinicians to monitor the patients for first 6 hours after initiation of fingolimod to decrease worse side effects. 

  19. Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

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    Juan Ignacio Rojas

    2012-08-01

    Full Text Available OBJECTIVE: To determine if the presence of oligoclonal bands (OB at early stages of multiple sclerosis was associated with higher brain atrophy, when compared with patients without OB. METHODS: Relapsing-remitting multiple sclerosis (RRMS patients with less than two years of disease onset and OB detection in cerebrospinal fluid (CSF were included. SIENAX was used for total brain volume (TBV, gray matter volume (GMV, and white matter volume (WMV. RESULTS: Forty patients were included, 29 had positive IgG-OB. No differences were found between positive and negative patients in gender, expanded disability status scale (EDSS, treatment received, and T2/T1 lesion load. TBV in positive IgG-OB patients was 1.5 mm³ x 10(6 compared with 1.64 mm³ x 10(6 in the negative ones (p=0.02. GMV was 0.51 mm³ x 10(6 in positive IgG-OB compared with 0.62 mm³ x 10(6 in negative ones (p=0.002. No differences in WMV (p=0.09 were seen. CONCLUSIONS: IgG-OB in the CSF was related to neurodegeneration magnetic resonance (MR markers in early RRMS.

  20. 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.

  1. Blood-Brain Barrier Permeability of Normal Appearing White Matter in Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Lund, Henrik; Krakauer, Martin; Skimminge, Arnold

    2013-01-01

    Background: Multiple sclerosis (MS) affects the integrity of the blood-brain barrier (BBB). Contrast-enhanced T1 weighted magnetic resonance imaging (MRI) is widely used to characterize location and extent of BBB disruptions in focal MS lesions. We employed quantitative T1 measurements before...

  2. Neurofunctional Correlates of Personality Traits in Relapsing-Remitting Multiple Sclerosis: An fMRI Study

    Science.gov (United States)

    Gioia, Maria C.; Cerasa, Antonio; Valentino, Paola; Fera, Francesco; Nistico, Rita; Liguori, Maria; Lanza, Pierluigi; Quattrone, Aldo

    2009-01-01

    Extraversion and Neuroticism are two fundamental dimensions of human personality that influence cognitive functioning in healthy subjects. Little is known about personality changes that may occur in patients with multiple sclerosis (MS) nor about, in particular, their neurofunctional basis. The aim of this study is to determine the impact of…

  3. Sequencing of disease-modifying therapies for relapsing-remitting multiple sclerosis: a theoretical approach to optimizing treatment.

    Science.gov (United States)

    Grand'Maison, Francois; Yeung, Michael; Morrow, Sarah A; Lee, Liesly; Emond, Francois; Ward, Brian J; Laneuville, Pierre; Schecter, Robyn

    2018-04-18

    Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

  4. Does Self-Efficacy Affect Cognitive Performance in Persons with Clinically Isolated Syndrome and Early Relapsing Remitting Multiple Sclerosis?

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    Peter Joseph Jongen

    2015-01-01

    Full Text Available In persons with multiple sclerosis (MS a lowered self-efficacy negatively affects physical activities. Against this background we studied the relationship between self-efficacy and cognitive performance in the early stages of MS. Thirty-three patients with Clinically Isolated Syndrome (CIS and early Relapsing Remitting MS (eRRMS were assessed for self-efficacy (MSSES-18, cognition (CDR System, fatigue (MFIS-5, depressive symptoms (BDI, disease impact (MSIS-29, and disability (EDSS. Correlative analyses were performed between self-efficacy and cognitive scores, and stepwise regression analyses identified predictors of cognition and self-efficacy. Good correlations existed between total self-efficacy and Power of Attention (r= 0.65; P< 0.001, Reaction Time Variability (r= 0.57; P< 0.001, and Speed of Memory (r= 0.53; P< 0.01, and between control self-efficacy and Reaction Time Variability (r= 0.55; P< 0.01. Total self-efficacy predicted 40% of Power of Attention, 34% of Reaction Time Variability, and 40% of Speed of Memory variabilities. Disease impact predicted 65% of total self-efficacy and 58% of control self-efficacy variabilities. The findings may suggest that in persons with CIS and eRRMS self-efficacy may positively affect cognitive performance and that prevention of disease activity may preserve self-efficacy.

  5. Symptoms and Association with Health Outcomes in Relapsing-Remitting Multiple Sclerosis: Results of a US Patient Survey

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    Angela E. Williams

    2014-01-01

    Full Text Available Background. A variety of symptoms have been reported, but the prevalence of specific symptoms in relapsing-remitting multiple sclerosis (RRMS, how they are related to one another, and their impact on patient reported outcomes is not well understood. Objective. To describe how symptoms of RRMS cooccur and their impact on patient-reported outcomes. Methods. Individuals who reported a physician diagnosis of RRMS in a large general health survey in the United States indicated the symptoms they experience because of RRMS and completed validated scales, including the work productivity and activity impairment questionnaire and either the SF-12v2 or SF-36v2. Symptom clusters were identified through hierarchical cluster analysis, and the relationship between clusters and outcomes was assessed through regression. Results. Fatigue, difficulty walking, and numbness were the most commonly reported symptoms. Seven symptom clusters were identified, and several were significantly related to patient reported outcomes. Pain, muscle spasms, and stiffness formed a cluster strongly related to physical quality of life; depression was strongly related to mental quality of life and cognitive difficulty was associated with work impairment. Conclusions. Symptoms in RRMS show a strong relationship with quality of life and should be taken into consideration in treatment decisions and evaluation of treatment success.

  6. Gray Matter Correlates of Cognitive Performance Differ between Relapsing-Remitting and Primary-Progressive Multiple Sclerosis.

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    Laura E Jonkman

    Full Text Available Multiple Sclerosis (MS is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS. Most patients experience a relapsing-remitting (RR course, while about 15-20% of patients experience a primary progressive (PP course. Cognitive impairment affects approximately 40-70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS and thirty-eight matched controls underwent neuropsychological (NP testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course.

  7. Elevated body temperature is linked to fatigue in an Italian sample of relapsing-remitting multiple sclerosis patients.

    Science.gov (United States)

    Leavitt, V M; De Meo, E; Riccitelli, G; Rocca, M A; Comi, G; Filippi, M; Sumowski, J F

    2015-11-01

    Elevated body temperature was recently reported for the first time in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls. In addition, warmer body temperature was associated with worse fatigue. These findings are highly novel, may indicate a novel pathophysiology for MS fatigue, and therefore warrant replication in a geographically separate sample. Here, we investigated body temperature and its association to fatigue in an Italian sample of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with our original report, we found elevated body temperature in the RRMS sample compared to healthy controls. Warmer body temperature was associated with worse fatigue, thereby supporting the notion of endogenous temperature elevations in patients with RRMS as a novel pathophysiological factor underlying fatigue. Our findings highlight a paradigm shift in our understanding of the effect of heat in RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although randomized controlled trials of cooling treatments (i.e., aspirin, cooling garments) to reduce fatigue in RRMS have been successful, consideration of endogenously elevated body temperature as the underlying target will enhance our development of novel treatments.

  8. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Siemonsen, Susanne; Wenzel, Damian

    2017-01-01

    BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic...... lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did...

  9. Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure.

    Science.gov (United States)

    Sumowski, James F; Leavitt, Victoria M

    2014-07-01

    To investigate whether (1) resting body temperature is elevated in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy individuals and patients with secondary progressive multiple sclerosis (SPMS), and (2) warmer body temperature is linked to worse fatigue in patients with RRMS. Cross-sectional study. Climate-controlled laboratory (∼22°C) within a nonprofit medical rehabilitation research center. Patients with RRMS (n=50), matched healthy controls (n=40), and patients with SPMS (n=22). Not applicable. Body temperature was measured with an aural infrared thermometer (normative body temperature for this thermometer, 36.75°C), and differences were compared across patients with RRMS and SPMS and healthy persons. Patients with RRMS completed measures of general fatigue (Fatigue Severity Scale [FSS]), as well as physical and cognitive fatigue (Modified Fatigue Impact Scale [MFIS]). There was a large effect of group (Pphysical fatigue (physical fatigue subscale of the MFIS; rp=.318, P=.026), but not cognitive fatigue (cognitive fatigue subscale of the MIFS; rp=-.017, P=.909). These are the first-ever demonstrations that body temperature is elevated endogenously in patients with RRMS and linked to worse fatigue. We discuss these findings in the context of failed treatments for fatigue in RRMS, including several failed randomized controlled trials (RCTs) of stimulants (modafinil). In contrast, our findings may help explain how RCTs of cooling garments and antipyretics (aspirin) have effectively reduced MS fatigue, and encourage further research on cooling/antipyretic treatments of fatigue in RRMS. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

    2014-05-01

    At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  11. Sjögren Syndrome Which Simulates Relapsing Remitting Multiple Sclerosis Clinical Features: Case Report

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    Haluk Gümüş

    2013-12-01

    Full Text Available Sjögren syndrome (SS is a chronic, inflammatory, autoimmune disease. It emerges as a dry mouth and eyes (sicca symptoms because, it fundamentally affects exocrine glands, frequently, salivary gland and lachrymal gland. Neurological involvement in Sjögren syndrome is observed in the approximately 20-25% of cases. 87% of the neurological involvements are peripheral nervous system involvement and around 13% of the neurological involvements are central nervous system involvement. Cerebral involvement represents heterogeneous features in terms of both localization (focal or diffuse and progress of the statement (acute, progressive or reversible. Affected central nervous system can show clinical and radiological signs similar to Multiple sclerosis (MS. In this paper, the case, which has a complaint of difficulty in walking and instability and MS like lesions in brain magnetic resonance imaging (MRI and is diagnosed as Sjögren syndrome by further research, is discussed

  12. Balancing the Demands of Two Tasks: An Investigation of Cognitive-Motor Dual-Tasking in Relapsing Remitting Multiple Sclerosis.

    Science.gov (United States)

    Butchard-MacDonald, Emma; Paul, Lorna; Evans, Jonathan J

    2018-03-01

    People with relapsing remitting multiple sclerosis (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance. This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls, and (2) dual-task decrements are associated with everyday dual-tasking difficulties. The impact of mood, fatigue, and disease severity on dual-tasking was also examined. A total of 34 PwRRMS and 34 matched controls completed cognitive (digit span) and balance (movement of center of pressure on Biosway on stable and unstable surfaces) tasks under single- and dual-task conditions. Everyday dual-tasking was measured using the Dual-Tasking Questionnaire. Mood was measured by the Hospital Anxiety & Depression Scale. Fatigue was measured via the Modified Fatigue Index Scale. No differences in age, gender, years of education, estimated pre-morbid IQ, or baseline digit span between groups. Compared with controls, PwRRMS showed significantly greater decrement in postural stability under dual-task conditions on an unstable surface (p=.007), but not a stable surface (p=.679). Balance decrement scores were not correlated with everyday dual-tasking difficulties or fatigue. Stable surface balance decrement scores were significantly associated with levels of anxiety (rho=0.527; p=.001) and depression (rho=0.451; p=.007). RRMS causes dual-tasking difficulties, impacting balance under challenging conditions, which may contribute to increased risk of gait difficulties and falls. The relationship between anxiety/depression and dual-task decrement suggests that emotional factors may be contributing to dual-task difficulties. (JINS, 2018, 24, 247-258).

  13. 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

  14. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

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    Andreas Keller

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

  15. Body temperature is elevated and linked to fatigue in relapsing-remitting multiple sclerosis, even without heat exposure

    Science.gov (United States)

    Sumowski, James F.; Leavitt, Victoria M.

    2014-01-01

    Objective To investigate whether resting body temperature is elevated and linked to fatigue in patients with relapsing-remitting multiple sclerosis (RRMS). Design Cross-sectional study investigating (a) differences in resting body temperature across RRMS, SPMS, and healthy groups, and (b) the relationship between body temperature and fatigue in RRMS patients. Setting Climate-controlled laboratory (~22°C) within a non-profit medical rehabilitation research center. Participants Fifty patients with RRMS, 40 matched healthy controls, and 22 patients with secondary-progressive MS (SPMS). Intervention None. Main Outcome Measure(s) Body temperature was measured with an aural infrared thermometer (normal body temperature for this thermometer is 36.75°C), and differences were compared across RRMS, SPMS, and healthy persons. RRMS patients completed measures of general fatigue (Fatigue Severity Scale; FSS), as well as physical and cognitive fatigue (Modified Fatigue Impact Scale; MFIS). Results There was a large effect of group (ptemperature was higher in RRMS patients (37.04°C±0.27) relative to healthy controls (36.83 ± 0.33; p = .009) and SPMS patients (36.75°C±0.39; p=.001). Warmer body temperature in RRMS patients was associated with worse general fatigue (FSS; rp=.315, p=.028) and physical fatigue (pMFIS; rp=.318, p=.026), but not cognitive fatigue (cMIFS; rp=−.017, p=.909). Conclusions These are the first-ever demonstrations that body temperature is elevated endogenously in RRMS patients, and linked to worse fatigue. We discuss these findings in the context of failed treatments for fatigue in RRMS, including several failed randomized controlled trials (RCTs) of stimulants (modafinil). In contrast, our findings may help explain how RCTs of cooling garments and antipyretics (aspirin) have effectively reduced MS fatigue, and encourage further research on cooling/antipyretic treatments of fatigue in RRMS. PMID:24561056

  16. Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

    Science.gov (United States)

    O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

    2015-04-01

    To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly

  17. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

    Directory of Open Access Journals (Sweden)

    Simon Zhornitsky

    Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

  18. Update on the cardiovascular profile of fingolimod in the therapy of relapsing-remitting multiple sclerosis (MS).

    Science.gov (United States)

    Meissner, Axel; Limmroth, Volker

    2016-07-01

    Fingolimod (FTY720) has been approved as the first oral representative of the class of sphingosine-1-phosphate (S1P) receptor modulators for the treatment of relapsing-remitting multiple sclerosis (MS). Besides inducing vaso-relaxation, fingolimod can also influence electrical conduction in the myocardium and vascular endothelium by having a transient negative chronotropic effect on the sinus node. Cardiac safety and tolerability of fingolimod in the cardiac sense were reviewed by analysing the data collected from the FREEDOMS and TRANSFORMS studies -both relevant studies for marketing authorisation, from their extension studies, as well as the clinical data collected from a practice-related MS patient cohort with cardiovascular risk factors and corresponding co-medication (FIRST study). The safety analyses on file gave no indication of any increased cardiovascular risk. The 2-3mmHg increase in blood pressure observed after the first dose of fingolimod has no therapeutic consequences. The first dose of 0.5mg fingolimod resulted in an average decrease in heart rate of 7-8beats/min. The onset of effect occurred approximately 1-2h after the first dose and the nadir was reached after approximately 4-5h. This negative chronotropic effect returned to normal after internalisation of the S1P1 receptors on maintenance therapy. There were no indications that patients with cardiac risk factors required closer observation beyond the monitoring recommended by the EMA following the first dose of fingolimod. Case study observations from the routine clinical setting show that patients accept this method of monitoring, which they assess as being a positive aspect of attentive medical care and concern. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Cost analysis of glatiramer acetate versus interferon-β for relapsing-remitting multiple sclerosis in patients with spasticity: the Escala study.

    Science.gov (United States)

    Sánchez-de la Rosa, Rainel; García-Bujalance, Laura; Meca-Lallana, José

    2015-12-01

    The Escala Study evidenced that the administration of glatiramer acetate for relapsing-remitting multiple sclerosis improved the spasticity of patients previously treated with interferon-β. However, whether such an improvement was translated into cost savings remained unclear. We therefore conducted a cost analysis of glatiramer acetate versus interferon-β in these patients with multiple sclerosis and spasticity. This cost analysis encompassed data from the observational Escala Study, which included patients with relapsing-remitting multiple sclerosis and spasticity whose treatment had been switched from interferon-β to glatiramer acetate. Costs prior to starting glatiramer acetate (interferon-β period) were compared to the subsequent six months on glatiramer acetate (glatiramer acetate period). The analysis was carried out following the recommendations for conducting pharmacoeconomic studies and from the Spanish National Health System perspective. Costs associated with multiple sclerosis treatment, spasticity treatment and relapse management were expressed in 2014 euros (€); a 7.5 % discount was applied-when needed-as stipulated in Spanish law. The management of relapsing-remitting multiple sclerosis, spasticity and relapses accounted for a 6-month cost per patient of 7,078.02€ when using interferon-β and 4,671.31€ when using glatiramer acetate. Switching from interferon-β to glatiramer acetate therefore represented a cost saving of 2,406.72€ per patient in favour of glatiramer acetate, which resulted from savings in treatment costs, relapse management and spasticity treatment of 1,890.02€, 430.48€ and 86.21€, respectively. The ratio of the costs during interferon-β was 1.5 times the costs during glatiramer acetate; thus, a fixed budget of 5,000,000€ would enable 1,070 patients to be treated with glatiramer acetate and only 706 patients with interferon-β. The treatment of relapsing-remitting multiple sclerosis with glatiramer acetate

  20. Cognitive performance in relapsing remitting multiple sclerosis: A longitudinal study in daily practice using a brief computerized cognitive battery

    Directory of Open Access Journals (Sweden)

    Jacquerye Philippe

    2011-06-01

    Full Text Available Abstract Background There is need for a cognitive test battery that can be easily used in clinical practice to detect or monitor cognitive performance in patients with multiple sclerosis (MS. In order to conduct, in this patient group, a preliminary investigation of the validity and utility of a brief computerized battery, the Cognitive Drug Research (CDR battery, we longitudinally assessed cognition in patients with relapsing remitting (RR MS. Methods Forty-three mildly disabled, clinically active RRMS patients were repeatedly assessed with the Digit Symbol Substitution Test (DSST, Paced Auditory Serial Addition Test (PASAT and five composite scores derived from the CDR computerized cognitive test system (CDR System: Power of Attention, Continuity of Attention, Quality of Working Memory, Quality of Episodic Memory and Speed of Memory. The Multiple Sclerosis Functional Composite (MSFC and Expanded Disability Status Scale (EDSS measured disability. Results The composite scores from the CDR battery generally showed excellent test-retest reliability over the repeated assessments, though was low on occasions for the Quality of Working Memory and Quality of Episodic Memory measures. The CDR measures tended to be highly correlated with other measures of cognition (DSST and PASAT and were also strongly related to disability (EDSS and MSFC. Baseline scores indicated large impairments to visual information processing speed and attention (DSST, Cohen's d 1.1; Power of Attention d 1.4 [reaction time on tasks of focussed and sustained attention], and a moderate impairment both to sustained attention (Continuity of Attention d 0.6 and complex information processing speed (Speed of memory d 0.7 [reaction time on tasks of working and episodic Memory], when compared to normative data derived from healthy volunteers enrolled in a series of separate, prior clinical trials. Working memory (Quality of Working Memory and episodic memory (Quality of Episodic Memory

  1. Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis.

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    Takuya Matsushita

    Full Text Available BACKGROUND: Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO, relapsing remitting multiple sclerosis (RRMS, and primary progressive MS (PPMS, and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis. METHODS/PRINCIPAL FINDINGS: We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND by multiplexed fluorescent bead-based immunoassay. Interleukin (IL-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients. CONCLUSIONS: Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell

  2. An Ultra-High Field Study of Cerebellar Pathology in Early Relapsing-Remitting Multiple Sclerosis Using MP2RAGE.

    Science.gov (United States)

    Fartaria, Mário João; OʼBrien, Kieran; Şorega, Alexandra; Bonnier, Guillaume; Roche, Alexis; Falkovskiy, Pavel; Krueger, Gunnar; Kober, Tobias; Bach Cuadra, Meritxell; Granziera, Cristina

    2017-05-01

    The aim of this study was to study focal cerebellar pathology in early stages of multiple sclerosis (MS) using ultra-high-field magnetization-prepared 2 inversion-contrast rapid gradient-echo (7T MP2RAGE). Twenty early-stage relapsing-remitting MS patients underwent an MP2RAGE acquisition at 7 T magnetic resonance imaging (MRI) (images acquired at 2 different resolutions: 0.58 × 0.58 × 0.58 mm, 7T_0.58, and 0.75 × 0.75 × 0.90 mm, 7T_0.75) and 3 T MRI (1.0 × 1.0 × 1.2 mm, 3T_1.0). Total cerebellar lesion load and volume and mean cerebellar lesion volume were compared across images using a Wilcoxon signed-rank test. Mean T1 relaxation times in lesions and normal-appearing tissue as well as contrast-to-noise ratio (CNR) measurements were also compared using a Wilcoxon signed-rank test. A multivariate analysis was applied to assess the contribution of MRI metrics to clinical performance in MS patients. Both 7T_0.58 and 7T_0.75 MP2RAGE showed significantly higher lesion load compared with 3T_1.0 MP2RAGE (P < 0.001). Plaques that were judged as leukocortical in 7T_0.75 and 3T_1.0 MP2RAGEs were instead identified as WM lesions in 7T_0.58 MP2RAGE. Cortical lesion CNR was significantly higher in MP2RAGEs at 7 T than at 3 T. Total lesion load as well as total and mean lesion volume obtained at both 7 T and 3 T MP2RAGE significantly predicted attention (P < 0.05, adjusted R = 0.5), verbal fluency (P < 0.01, adjusted R = 0.6), and motor performance (P = 0.01, adjusted R = 0.7). This study demonstrates the value of 7 T MP2RAGE to study the cerebellum in early MS patients. 7T_0.58 MP2RAGE provides a more accurate anatomical description of white and gray matter pathology compared with 7T_0.75 and 3T_1.0 MP2RAGE, likely due to the improved spatial resolution, lower partial volume effects, and higher CNR.

  3. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Pierre Branger

    Full Text Available The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL or second-line (SL disease-modifying drugs (DMDs and brain volume changes over time in RRMS.We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed.Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57--0.15; P = 0.02. Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046 but not between FLDMDs (-0.33%/y and placebo (P = 0.11 or between FLDMDs and SLDMDs (P = 0.49. Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001 and FLDMDs (-0.46%/y, P<0.005, but no difference was detected between FLDMDs and placebo (P = 0.12.SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.

  4. 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

    DEFF Research Database (Denmark)

    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...

  5. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    Science.gov (United States)

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  6. [The influence of age and illness duration on cognitive impairment in aging patients with relapsing-remitting multiple sclerosis (RR-MS)].

    Science.gov (United States)

    Leclercq, Eugénie; Cabaret, Maryline; Guilbert, Alma; Jougleux, Caroline; Vermersch, Patrick; Moroni, Christine

    2014-09-01

    The aim of this study was to dissociate age and duration of illness effects on cognitive impairment of patients with relapsing-remitting multiple sclerosis. Cognitive impairment among patients with multiple sclerosis (MS) is well known. However, few studies were devoted to assess the respective role of disease duration and age on cognitive functions in MS patients. Therefore, two studies were carried out on relapsing-remitting MS (RR-MS) patients using some tests of the BCcogSEP--a French test battery evaluating cognitive functions in MS. The cognitive deficits of RR-MS patients aged 50 years and over and whose symptoms had been present for more than 20 years were more severe than those of MS patients with a shorter illness duration (less than 10 years) or matched-age control participants. The more impaired cognitive functions were information-processing speed, episodic memory, verbal fluency and attention. On the other hand, cognitive performances of young RR-MS patients were similar to those of older RR-MS patients when all patients had the same illness duration (8 years in this study). Older patients even achieved better performance than younger ones on verbal fluency. This can be partly explained by the theory of cognitive reserve, as reported in previous cognitive aging studies. In RR-MS patients, the influence of illness duration seems to be a predominant factor in the development of cognitive impairment.

  7. An intensive social cognitive program (can do treatment) in people with relapsing remitting multiple sclerosis and low disability: a randomized controlled trial protocol.

    Science.gov (United States)

    Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Evers, Silvia; Duyverman, Lotte; Valkenburg-Vissers, Joyce; Cornelissen, Job; Bos, Michel; van Droffelaar, Maarten; Lemmens, Wim A; Donders, Rogier; van der Zande, Anneke; Visser, Leo H

    2016-05-28

    In people with multiple sclerosis (MS) disabilities and limitations may negatively affect self-efficacy. Lowered self-efficacy has been associated with decreases in health-related quality of life, physical activity and cognitive performance. In an explorative observational study we found that a 3-day intensive social cognitive program (Can Do Treatment [CDT]) with the participation of support partners was followed by substantial increases in self-efficacy control and health-related quality of life 6 months after treatment in those people with MS who had relapsing remitting disease and low disability. CDT is a sociologically oriented approach, its goal is to uncover and promote existing capabilities, and the notion "stressor" is the central concept. CDT's components are plenary group sessions, small group sessions, consultations, a theatre evening, and start of the day with a joint activity. The small group sessions form the actual training. Depending on their individual goals the participants join the training groups 'Body', 'Feeling' or 'Life', to work out their aims and to reduce their stressors. The multidisciplinary team includes a psychiatrist, psychiatric nurse, neurologist, specialized MS nurse, physiotherapist, dance therapist, and a person with MS. To evaluate the (cost)effectiveness of CDT in persons with relapsing remitting MS and low disability we perform a single-centre, randomized controlled trial in 140 patients, with or without support partners. The primary outcome is self-efficacy control. The secondary outcomes are self-efficacy function, health-related quality of life, autonomy and participation, anxiety, depression, cost effectiveness and cost utility. The tertiary outcome is care-related strain to support partners. Outcomes are assessed at baseline and at 1, 3 and 6 months after CDT. This randomized controlled trial will adequately evaluate the clinical and cost effectiveness of a 3-day intensive social cognitive program in people with

  8. The MS@Work study: a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis.

    Science.gov (United States)

    van der Hiele, Karin; van Gorp, Dennis A M; Heerings, Marco A P; van Lieshout, Irma; Jongen, Peter J; Reneman, Michiel F; van der Klink, Jac J L; Vosman, Frans; Middelkoop, Huub A M; Visser, Leo H

    2015-08-12

    Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading up to unemployment, many may experience a reduction in hours or work responsibilities and increased time missed from work. The MS@Work study examines various factors that may influence work participation in relapsing-remitting MS patients, including disease-related factors, the working environment and personal factors. The MS@Work study is a multicenter, 3-year prospective observational study on work participation in patients with relapsing-remitting MS. We aim to include 350 patients through 15-18 MS outpatient clinics in the Netherlands. Eligible participants are 18 years and older, and either currently employed or within three years since their last employment. At baseline and after 1, 2 and 3 years, the participants are asked to complete online questionnaires (including questions on work participation, work problems and accommodations, cognitive and physical ability, anxiety, depression, psychosocial stress, quality of life, fatigue, empathy, personality traits and coping strategies) and undergo cognitive and neurological examinations. After six months, patients are requested to only complete online questionnaires. Patient perspectives on maintaining and improving work participation and reasons to stop working are gathered through semi-structured interviews in a sub-group of patients. Prospective studies with long-term follow-up on work participation in MS are rare, or take into account a limited number of factors. The MS@Work study provides a 3-year follow-up on various factors that may influence work participation in patients with relapsing-remitting MS. We aim to identify factors that relate to job loss and to provide information about preventative measures for physicians

  9. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

    2007-01-01

    callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated......Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar...... to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical...

  10. Clinical efficacy of BG-12 (dimethyl fumarate) in patients with relapsing-remitting multiple sclerosis: subgroup analyses of the CONFIRM study.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2013-09-01

    In the phase 3, randomized, placebo-controlled and active reference (glatiramer acetate) comparator CONFIRM study in patients with relapsing-remitting multiple sclerosis, oral BG-12 (dimethyl fumarate) reduced the annualized relapse rate (ARR; primary endpoint), as well as the proportion of patients relapsed, magnetic resonance imaging lesion activity, and confirmed disability progression, compared with placebo. We investigated the clinical efficacy of BG-12 240 mg twice daily (BID) and three times daily (TID) in patient subgroups stratified according to baseline demographic and disease characteristics including gender, age, relapse history, McDonald criteria, treatment history, Expanded Disability Status Scale score, T2 lesion volume, and gadolinium-enhancing lesions. BG-12 treatment demonstrated generally consistent benefits on relapse-related outcomes across patient subgroups, reflecting the positive findings in the overall CONFIRM study population. Treatment with BG-12 BID and TID reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in all subgroups analyzed. Reductions in ARR with BG-12 BID versus placebo ranged from 34% [rate ratio 0.664 (95% confidence interval 0.422-1.043)] to 53% [0.466 (0.313-0.694)] and from 13% [0.870 (0.551-1.373)] to 67% [0.334 (0.226-0.493)] with BG-12 TID versus placebo. Treatment with glatiramer acetate reduced the ARR and the proportion of patients relapsed at 2 years compared with placebo in most patient subgroups. The results of these analyses indicate that treatment with BG-12 is effective on relapses across a broad range of patients with relapsing-remitting multiple sclerosis with varied demographic and disease characteristics.

  11. Investigating the Relationship Between Selective Attention and Cognitive Flexibility With Balance in Patients With Relapsing-Remitting Multiple Sclerosis

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    Vali Shiri

    2018-01-01

    Conclusion A significant relationship between selective attentions to balance demonstrates that appropriately designed interventions to repair the attention, can decrease the balance problem in patients with MS. One of the possible reasons for this relationship can be found in the brain system that attention circuits are interacting with equilibrium systems, and any defect in selective attention leads to a loss of balance. Patients with MS experience constant imbalance due to cerebral plaques and relapsing-remitting periods, and in addition to rehabilitation of the balance system, cognitive systems such as attention should be treated.

  12. Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

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    Cleanthous, Sophie; Strzok, Sara; Pompilus, Farrah; Cano, Stefan; Marquis, Patrick; Cohan, Stanley; Goldman, Myla D; Kresa-Reahl, Kiren; Petrillo, Jennifer; Castrillo-Viguera, Carmen; Cadavid, Diego; Chen, Shih-Yin

    2018-01-01

    ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

  13. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

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    Bellmann-Strobl, J.; Paul, F.; Aktas, O.; Zipp, F. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); Stiepani, H.; Bohner, G.; Klingebiel, R. [Charite - University Medicine Berlin, Department of Neuroradiology, Berlin (Germany); Wuerfel, J. [Charite - University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Cecilie Vogt Clinic for Neurology, Berlin (Germany); University Schleswig-Holstein, Institute of Neuroradiology, Campus Luebeck, Kiel (Germany); Warmuth, C. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Wandinger, K.P. [Charite - University Medicine Berlin, Department of Neurology, Berlin (Germany)

    2009-08-15

    The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0{+-}7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon {beta}-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p<0.05) and correlated to the MSFC score (r=0.476, p<0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p<0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. (orig.)

  14. MR spectroscopy (MRS) and magnetisation transfer imaging (MTI), lesion load and clinical scores in early relapsing remitting multiple sclerosis: a combined cross-sectional and longitudinal study

    International Nuclear Information System (INIS)

    Bellmann-Strobl, J.; Paul, F.; Aktas, O.; Zipp, F.; Stiepani, H.; Bohner, G.; Klingebiel, R.; Wuerfel, J.; Warmuth, C.; Wandinger, K.P.

    2009-01-01

    The purpose of this study was to correlate magnetic resonance imaging (MRI)-based lesion load assessment with clinical disability in early relapsing remitting multiple sclerosis (RRMS). Seventeen untreated patients (ten women, seven men; mean age 33.0±7.9 years) with the initial diagnosis of RRMS were included for cross-sectional as well as longitudinal (24 months) clinical and MRI-based assessment in comparison with age-matched healthy controls. Conventional MR sequences, MR spectroscopy (MRS) and magnetisation transfer imaging (MTI) were performed at 1.5 T. Lesion number and volume, MRS and MTI measurements for lesions and normal appearing white matter (NAWM) were correlated to clinical scores [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC)] for monitoring disease course after treatment initiation (interferon β-1a). MTI and MRS detected changes [magnetisation transfer ratio (MTR), N-acetylaspartate (NAA)/creatine ratio] in NAWM over time. EDSS and lesional MTR increases correlated throughout the disease course. Average MTR of NAWM raised during the study (p<0.05) and correlated to the MSFC score (r=0.476, p<0.001). At study termination, NAA/creatine ratio of NAWM correlated to the MSFC score (p<0.05). MTI and MRS were useful for initial disease assessment in NAWM. MTI and MRS correlated with clinical scores, indicating potential for monitoring the disease course and gaining new insights into treatment-related effects. (orig.)

  15. Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study

    Directory of Open Access Journals (Sweden)

    Fredrikson Sten

    2010-11-01

    Full Text Available Abstract Background Glatiramer acetate (GA and interferon-beta (INFb are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS. Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. Methods 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32, fatigue (Fatigue Impact Scale [FIS] and depressed mood (Beck Depression Inventory-Short Form [BDI-SF] at baseline and 6 and 12 months after start of GA treatment. Results At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p Conclusions In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue.

  16. Relationship between working hours and power of attention, memory, fatigue, depression and self-efficacy one year after diagnosis of clinically isolated syndrome and relapsing remitting multiple sclerosis.

    Science.gov (United States)

    Jongen, Peter Joseph; Wesnes, Keith; van Geel, Björn; Pop, Paul; Sanders, Evert; Schrijver, Hans; Visser, Leo H; Gilhuis, H Jacobus; Sinnige, Ludovicus G; Brands, Augustina M

    2014-01-01

    The role of cognitive domain dysfunction with respect to vocational changes in persons with Clinically Isolated Syndrome (CIS) and early Relapsing Remitting Multiple Sclerosis (eRRMS) is insufficiently known. We investigated thirty-three patients--14 CIS, 19 eRRMS -, mean (standard deviation [SD]) time since diagnosis 13.5 (4.8) months and mean (SD) Expanded Disability Status Scale (EDSS) score 1.3 (1.1). Patients were assessed on the CDR System, a set of automated tests of cognitive function, which yielded scores for Power of Attention (ms), Continuity of Attention (#), Working Memory (SI), Episodic Memory (#) and Speed of Memory (ms). Work-related items and the confounding variables fatigue, depression, disease impact and self-efficacy, were assessed by self-report questionnaires. Patients had poorer Power of Attention compared to normative data (1187 [161.5] vs. 1070 [98.6]; PMemory (4043 [830.6]) vs. 2937 [586.1]; PAttention (Pearson r =  -0.42; PMemory (r = 0.42; PAttention (1247 vs. 1116 ms; PMemory (1.35 vs. 1.57; pAttention and Speed of Memory are reduced, that Power of Attention and Memory are associated with a capability of working less hours, and that fatigue, depression and disease impact may negatively, and self-efficacy positively affect working hours.

  17. Daclizumab high-yield process reduced the evolution of new gadolinium-enhancing lesions to T1 black holes in patients with relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Radue, E-W; Sprenger, T; Vollmer, T; Giovannoni, G; Gold, R; Havrdova, E; Selmaj, K; Stefoski, D; You, X; Elkins, J

    2016-02-01

    In the SELECT study, treatment with daclizumab high-yield process (DAC HYP) versus placebo reduced the frequency of gadolinium-enhancing (Gd(+) ) lesions in patients with relapsing-remitting multiple sclerosis (RRMS). The objective of this post hoc analysis of SELECT was to evaluate the effect of DAC HYP on the evolution of new Gd(+) lesions to T1 hypointense lesions (T1 black holes). SELECT was a randomized double-blind study of subcutaneous DAC HYP 150 or 300 mg or placebo every 4 weeks. Magnetic resonance imaging (MRI) scans were performed at baseline and weeks 24, 36 and 52 in all patients and monthly between weeks 4 and 20 in a subset of patients. MRI scans were evaluated for new Gd(+) lesions that evolved to T1 black holes at week 52. Data for the DAC HYP groups were pooled for analysis. Daclizumab high-yield process reduced the number of new Gd(+) lesions present at week 24 (P = 0.005) or between weeks 4 and 20 (P = 0.014) that evolved into T1 black holes at week 52 versus placebo. DAC HYP treatment also reduced the percentage of patients with Gd(+) lesions evolving to T1 black holes versus placebo. Treatment with DAC HYP reduced the evolution of Gd(+) lesions to T1 black holes versus placebo, suggesting that inflammatory lesions that evolved during DAC HYP treatment are less destructive than those evolving during placebo treatment. © 2016 EAN.

  18. Using mental visual imagery to improve autobiographical memory and episodic future thinking in relapsing-remitting multiple sclerosis patients: A randomised-controlled trial study.

    Science.gov (United States)

    Ernst, Alexandra; Blanc, Frédéric; De Seze, Jérôme; Manning, Liliann

    2015-01-01

    The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients. Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n = 17), who followed the MVI programme, (ii) the verbal control (n = 10), who followed a sham verbal programme, and (iii) the stability groups (n = 13), who underwent the AM/EFT test twice, with no intervention in between. AI's second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits. The control and stability groups' results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients' comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT.

  19. 3T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing-remitting multiple sclerosis: a 3-year pilot study.

    Science.gov (United States)

    Zhang, Y; Metz, L M; Yong, V W; Mitchell, J R

    2010-10-15

    Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Lesion-to-ventricle distance and other risk factors for the persistence of newly formed black holes in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Papadopoulou, Athina; Menegola, Milena; Kuhle, Jens; Ramagopalan, Sreeram V; D'Souza, Marcus; Sprenger, Till; Radue, Ernst-Wilhelm; Kappos, Ludwig; Yaldizli, Özgür

    2014-03-01

    Progenitor cells from the subventricular zone (SVZ) of the lateral ventricles are assumed to contribute to remyelination and resolution of black holes (BHs) in multiple sclerosis (MS). This process may depend on the distance between the lesion and the SVZ. The objective of this paper is to investigate the relationship between lesion-to-ventricle (LV) distance and persistence of new BHs. We analysed the magnetic resonance images (MRIs) of 289 relapsing-remitting (RR) MS patients, obtained during a multi-centre, placebo-controlled phase II trial over one year. Overall, 112/289 patients showed 367 new BHs at the beginning of the trial. Of these, 225 were located in 94/112 patients at the level of the lateral ventricles on axial MRIs and included in this analysis. In total, 86/225 (38%) BHs persisted at month 12. LV distance in persistent BHs (PBHs) was not longer than in transient BHs. In fact PBHs tended to be closer to the SVZ than transient BHs. A generalised linear mixed multivariate model adjusted for BHs clustered within a patient and including patient- as well as lesion-specific factors revealed size, ring contrast enhancement, and shorter LV distance as independent predictors for BH persistence. Location of BHs close to the lateral ventricles does not appear to favourably influence the resolution of new BHs in RRMS.

  1. Characteristics of lesional and extra-lesional cortical grey matter in relapsing-remitting and secondary progressive multiple sclerosis: A magnetisation transfer and diffusion tensor imaging study.

    Science.gov (United States)

    Yaldizli, Özgür; Pardini, Matteo; Sethi, Varun; Muhlert, Nils; Liu, Zheng; Tozer, Daniel J; Samson, Rebecca S; Wheeler-Kingshott, Claudia Am; Yousry, Tarek A; Miller, David H; Chard, Declan T

    2016-02-01

    In multiple sclerosis (MS), diffusion tensor and magnetisation transfer imaging are both abnormal in lesional and extra-lesional cortical grey matter, but differences between clinical subtypes and associations with clinical outcomes have only been partly assessed. To compare mean diffusivity, fractional anisotropy and magnetisation transfer ratio (MTR) in cortical grey matter lesions (detected using phase-sensitive inversion recovery (PSIR) imaging) and extra-lesional cortical grey matter, and assess associations with disability in relapse-onset MS. Seventy-two people with MS (46 relapsing-remitting (RR), 26 secondary progressive (SP)) and 36 healthy controls were included in this study. MTR, mean diffusivity and fractional anisotropy were measured in lesional and extra-lesional cortical grey matter. Mean fractional anisotropy was higher and MTR lower in lesional compared with extra-lesional cortical grey matter. In extra-lesional cortical grey matter mean fractional anisotropy and MTR were lower, and mean diffusivity was higher in the MS group compared with controls. Mean MTR was lower and mean diffusivity was higher in lesional and extra-lesional cortical grey matter in SPMS when compared with RRMS. These differences were independent of disease duration. In multivariate analyses, MTR in extra-lesional more so than lesional cortical grey matter was associated with disability. Magnetic resonance abnormalities in lesional and extra-lesional cortical grey matter are greater in SPMS than RRMS. Changes in extra-lesional compared with lesional cortical grey matter are more consistently associated with disability. © The Author(s), 2015.

  2. Focal cortical thinning in patients with stable relapsing-remitting multiple sclerosis. Cross-sectional-based novel estimation of gray matter kinetics

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    Orbach, Lior; Menascu, Shay; Hoffmann, Chen; Achiron, Anat [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel); Tel-Aviv University, Sackler School of Medicine, Tel-Aviv (Israel); Miron, Shmuel [Sheba Medical Center, Multiple Sclerosis Center, Tel-Hashomer (Israel)

    2018-02-15

    The aim of our study is to identify radiological patterns of cortical gray matter atrophy (CGMA) that correlate with disease duration in patients with relapsing-remitting multiple sclerosis (RRMS). RRMS patients were randomly selected from the Sheba Multiple Sclerosis (MS) center computerized data registry based on stratification of disease duration up to 10 years. Patients were scanned by 3.0 T (Signa, GE) MRI, using a T1 weighted 3D high resolution, FSPGR, MS protocol. Neurological disability was assessed by the Expanded Disability Status Scale (EDSS). FreeSurfer was used to obtain brain volumetric segmentation and to perform cortical thickness surface-based analysis. Clusters of change in cortical thickness with correlation to disease duration were produced. Two hundred seventy-one RRMS patients, mean ± SD age 33.0 ± 7.0 years, EDSS 1.6 ± 1.2, disease duration 5.0 ± 3.4 years. Cortical thickness analysis demonstrated focal areas of cerebral thinning that correlated with disease duration. Seven clusters accounting for 11.7% of the left hemisphere surface and eight clusters accounting for 10.6% of the right hemisphere surface were identified, with cluster-wise probability of p < 0.002 and p < 0.02, respectively.The clusters included bilateral involvement of areas within the cingulate, precentral, postcentral, paracentral, superior-parietal, superior-frontal gyri and insular cortex. Mean and cluster-wise cortical thickness negatively correlated with EDSS score, p < 0.001, with stronger Spearman rho for cluster-wise measurements. We identified CGMA patterns in sensitive brain regions which give insight and better understanding of the progression of cortical gray matter loss in relation to dissemination in space and time. These patterns may serve as markers to modulate therapeutic interventions to improve the management of MS patients. (orig.)

  3. The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients.

    Science.gov (United States)

    Bonnier, Guillaume; Maréchal, Benedicte; Fartaria, Mário João; Falkowskiy, Pavel; Marques, José P; Simioni, Samanta; Schluep, Myriam; Du Pasquier, Renaud; Thiran, Jean-Philippe; Krueger, Gunnar; Granziera, Cristina

    2017-01-01

    Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI) metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients. Thirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA) tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue. In patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter ( p  = 0.005) and a decrease of T1 relaxation times in the pallidum ( p  decrease in T1 relaxation time ( p -value  0.4, p  < 0.05). In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at early MS stages as suggested by histopathological studies.

  4. Functional cortical changes in relapsing-remitting multiple sclerosis at amplitude configuration: a resting-state fMRI study

    Directory of Open Access Journals (Sweden)

    Liu H

    2016-11-01

    Full Text Available Heng Liu,1,* Hua Chen,1,* Bo Wu,1 Tijiang Zhang,1 Jinhui Wang,2,3 Kexin Huang,1 Ganjun Song,1 Jian Zhan4 1Department of Radiology, Affiliated Hospital of Zunyi Medical University, Medical Imaging Center of Guizhou Province, Zunyi, Guizhou, 2Department of Psychology, Hangzhou Normal University, 3Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou, 4Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to explore the amplitude of spontaneous brain activity fluctuations in patients with relapsing–remitting multiple sclerosis (RRMS using the amplitude of low-frequency fluctuation (ALFF method. Methods: ALFF and SPM8 were utilized to assess alterations in regional spontaneous brain activities in patients with RRMS in comparison with healthy controls (HCs. The beta values of altered brain regions between patients with RRMS and HCs were extracted, and a receiver operating characteristic (ROC curve was generated to calculate the sensitivities and specificities of these different brain areas for distinguishing patients with RRMS from HCs. Pearson correlation analyses were applied to assess the relationships between the beta values of altered brain regions and disease duration and Expanded Disability Status Scale (EDSS score. Patients and participants: A total of 18 patients with RRMS (13 females; five males and 18 sex-, age-, and education-matched HCs (14 females; four males were recruited for this study. Measurements and results: Compared with HCs, patients with RRMS showed higher ALFF responses in the right fusiform gyrus (Brodmann area [BA] 37 and lower ALFF responses in the bilateral anterior cingulate cortices (BA 24 and 32, bilateral heads of the caudate nuclei, and bilateral brainstem. The ROC analysis revealed that the beta values of these abnormal brain areas

  5. Fadiga na forma remitente recorrente da esclerose múltipla Fatigue in multiple sclerosis relapsing-remitting form

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    MARIA FERNANDA MENDES

    2000-06-01

    Full Text Available Foram avaliados 95 pacientes com forma remitente-recorrente da esclerose múltipla quanto à presença de fadiga. A Escala de Severidade de Fadiga foi aplicada em todos os pacientes. Em 64 pacientes (67,4% a fadiga foi encontrada. Não observamos diferenças clínicas quanto ao gênero, idade, grau de incapacidade funcional e depressão, nos pacientes com e sem fadiga. Foi encontrada correlação entre ansiedade e tempo de doença com a presença de fadiga. Ao analisarmos estas variáveis quanto à intensidade da fadiga, observamos haver associação entre fadiga grave e maior incapacidade funcional.In 95 patients with the remitting-relapsing form of multiple sclerosis we investigated fatigue. All of them were evaluated with the Fatigue Severity Scale and we found it in 64 patients (67.4%. Gender, age, depression and fuctional incapacity was not predictive of fatigue occurrence, while anxiety and time of disease seems to be correlated with it. When we analysed the fatigue severity, a correlation between the EDSS and the increasing fatigue severity was found.

  6. GLATIRAMER ACETATE IS A FIRST-LINE DUAL-ACTION DRUG FOR THE TREATMENT OF RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    T. E. Shmidt

    2016-01-01

    Full Text Available Multiple sclerosis (MS is the most common and potentially disabling disease of the central nervous system in young people. Not only inflammatory, but also neurodegenerative processes are involved in the pathogenesis of MS. The use of MS-modifying drugs (MSMDs  has led to a substantial reduction in the frequency of MS exacerbations and to the slower development of irreversible neurological deficit. Glatiramer acetate is one of the MSMDs of first choice and has a dual (anti-inflammatory and neuroprotective action. The drug has proven to be effective and safe if administered long-term. Therapy with glatiramer acetate has been established to promote the production of anti-inflammatory cytokines and neurotrophic factors, which prevent the development of a degenerative process and stimulate remyelination, and to slow the progression of cerebral atrophy. Experimental findings suggest that the drug improves the processes of neurogenesis.The efficiency of treatment is known to be associated with patient medication adherence. This largely depends on the frequency and route of drug administration and on the development of adverse events (AEs. To improve treatment adherence to glatiramer acetate, its new 40-mg formulation has been designed, which allows it to be administered only thrice weekly. The use of the formulation has demonstrated its efficacy and safety and resulted in a considerable reduction in the incidence rate of AEs.

  7. 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.

  8. The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Georgios Tsivgoulis

    Full Text Available The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS using available randomized-controlled trial (RCT data.We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4. The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001. We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19 nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16. In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001 and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001. However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA.DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.

  9. Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.

    Science.gov (United States)

    González Gómez, A; García-Ben, A; Soler García, A; García-Basterra, I; Padilla Parrado, F; García-Campos, J M

    2017-03-15

    The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON. Copyright © 2017 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Progression of a series of patients with relapsing-remitting multiple sclerosis treated for 7 years with natalizumab using the "no evidence of disease activity" parameter.

    Science.gov (United States)

    Pato Pato, A; Costa Arpín, E; Rodríguez Regal, A; Rodríguez Constenla, I; Cimas Hernando, I; Muñoz Pousa, I; Naya Ríos, L; Lorenzo González, J R; Amigo Jorrín, M C; Prieto González, J M

    2018-05-10

    The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. Natalizumab is highly effective as measured by the NEDA long-term remission parameter. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility.

    Science.gov (United States)

    Montgomery, Stephen M; Kusel, Jeanette; Nicholas, Richard; Adlard, Nicholas

    2017-09-01

    Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis. A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs. Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient. When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of

  12. A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK.

    Science.gov (United States)

    Montgomery, Stephen M; Maruszczak, Maciej J; Slater, David; Kusel, Jeanette; Nicholas, Richard; Adlard, Nicholas

    2017-05-01

    Two disease-modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyze the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported. A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores. Individual patient characteristics were taken from the RES sub-groups of the pivotal trials for fingolimod. Utility data were in line with previous models. Published costs were inflated to NHS cost year 2015. Owing to the confidential patient access scheme (PAS) discount applied to fingolimod in the UK, a range of discount levels were applied to the fingolimod list price, to capture the likelihood of natalizumab being cost-effective in a real-world setting. At the lower National Institute of Health and Care Excellence (NICE) threshold of £20,000/quality-adjusted life year (QALY), fingolimod only required a discount greater than 0.8% of list price to be cost-effective. At the upper threshold of £30,000/QALY employed by the NICE, fingolimod was cost-effective if the confidential discount is greater than 2.5%. Sensitivity analyses conducted using fingolimod list-price showed the model to be most sensitive to changes in the cost of each drug, particularly fingolimod. The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.

  13. Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.

    Science.gov (United States)

    Bonavita, S; Sacco, R; Della Corte, M; Esposito, S; Sparaco, M; d'Ambrosio, A; Docimo, R; Bisecco, A; Lavorgna, L; Corbo, D; Cirillo, S; Gallo, A; Esposito, F; Tedeschi, G

    2015-01-01

    To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

  14. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study.

    Science.gov (United States)

    Giovannoni, Gavin; Soelberg Sorensen, Per; Cook, Stuart; Rammohan, Kottil; Rieckmann, Peter; Comi, Giancarlo; Dangond, Fernando; Adeniji, Abidemi K; Vermersch, Patrick

    2017-08-01

    In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3.5 mg/kg or placebo, with blind maintained. A total of 806 patients were assigned to treatment. Adverse event rates were generally similar between groups, but lymphopenia Grade ⩾ 3 rates were higher with cladribine than placebo (Grade 4 lymphopenia occurred infrequently). In patients receiving cladribine 3.5 mg/kg in CLARITY and experiencing lymphopenia Grade ⩾ 3 in the Extension, >90% of those treated with cladribine 3.5 mg/kg and all treated with placebo in the Extension, recovered to Grade 0-1 by study end. Cladribine treatment in CLARITY produced efficacy improvements that were maintained in patients treated with placebo in the Extension; in patients treated with cladribine 3.5 mg/kg in CLARITY, approximately 75% remained relapse-free when given placebo during the Extension. Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

  15. Long-term effects of cladribine tablets on MRI activity outcomes in patients with relapsing-remitting multiple sclerosis: the CLARITY Extension study.

    Science.gov (United States)

    Comi, Giancarlo; Cook, Stuart; Rammohan, Kottil; Soelberg Sorensen, Per; Vermersch, Patrick; Adeniji, Abidemi K; Dangond, Fernando; Giovannoni, Gavin

    2018-01-01

    The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference -0.33, 97.5% confidence interval -0.33-0.00; p MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537 .

  16. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Ann J. Ligocki

    2015-10-01

    Full Text Available * These authors contributed equally to the work in this manuscript.We have previously identified a distinct class of antibodies expressed by B cells in the cerebrospinal fluid (CSF of early and established relapsing remitting multiple sclerosis (RRMS patients that is not observed in healthy donors. These antibodies contain a unique pattern of mutations in six codons along VH4 antibody genes that we termed the antibody gene signature (AGS. In fact, patients who have such B cells in their CSF are identified as either having RRMS or developing RRMS in the future. As mutations in antibody genes increase antibody affinity for particular antigens, the goal for this study was to investigate whether AGS+ antibodies bind to brain tissue antigens. Single B cells were isolated from the CSF of 10 patients with early or established RRMS. We chose 32 of these B cells that expressed antibodies enriched for the AGS for further study. We generated monoclonal full-length recombinant human antibodies (rhAbs and used both immunological assays and immunohistochemistry to investigate the capacity of these AGS+ rhAbs to bind brain tissue antigens. AGS+ rhAbs did not recognize myelin tracts in the corpus callosum. Instead, AGS+ rhAbs recognized neuronal nuclei and/or astrocytes, which are prevalent in the cortical gray matter. This pattern was unique to the AGS+ antibodies from early and established RRMS patients, as AGS+ antibodies from an early neuromyelitis optica patient did not display the same reactivity. Prevalence of CSF-derived B cells expressing AGS+ antibodies that bind to these cell types may be an indicator of gray matter-directed autoimmunity in early and established RRMS patients.

  17. Impact of natalizumab treatment on fatigue, mood and aspects of cognition in relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Annett eKunkel

    2015-05-01

    Full Text Available Background/ObjectiveFatigue, cognitive and affective disorders are relevant symptoms in Multiple Sclerosis (MS. The treatment with Natalizumab has a positive effect on physical disabilities in patients with RRMS. Some studies describe improvements in cognition and fatigue over one year of treatment. Only little is known about longer treatment effects especially on fatigue, but also on cognition and mood. Therefore the present retrospective open label observational study investigates the effect of Natalizumab on fatigue, attention and depression over a treatment period of two years. Methods 51 RRMS patients that were treated with Natalizumab (male = 11, female = 40; mean age: 33,9+9,1 years were included. The neuropsychological assessment consisted of different tests of attention (TAP: alertness, divided attention, flexibility, SDMT, PASAT, fatigue (WEIMUS, FSMC and depression (CES-D. The assessments occurred immediately before the first administration of Natalizumab, after one and two years of treatment. ResultsSignificant improvements were found in aspects of attention and depression from baseline to follow-up 1 (alertness: reaction time (RT cued, p < 0.05; divided attention: visual RT, p < 0.05; SDMT: p = 0.05; CES-D: p < 0.05 and from baseline to follow-up 2 (divided attention: visual RT: p < 0.001; errors: p < 0.01, omissions: p < 0.05; flexibility: RT, p < 0.05; SDMT: p < 0.01; CES-D: p < 0.05. No significant changes were detected in fatigue probably because of the small sample size especially in the second year of treatment (WEIMUS: N = 16, FSMC: N = 8. Conclusion The results show a positive effect of Natalizumab on attention in patients with RRMS and for the first time also in depression after two years of observation and support the efficacy of the treatment over two years. More research is needed for fatigue.

  18. The experience of transitioning from relapsing remitting to secondary progressive multiple sclerosis: views of patients and health professionals.

    Science.gov (United States)

    O'Loughlin, Emer; Hourihan, Susan; Chataway, Jeremy; Playford, E Diane; Riazi, Afsane

    2017-09-01

    The majority of people with multiple sclerosis (pwMS) initially present with discreet periods of relapses followed by partial remission of symptoms (RRMS). Over time, most pwMS transition to secondary progressive MS (SPMS), characterized by a gradual accumulation of disability. This study aimed to explore the experiences, coping and needs associated with transitioning from RRMS to SPMS. Data were collected via semi-structured interviews with nine pwMS and seven specialist MS health professionals (HPs). Thematic analysis was used to analyze the data. Four major themes were identified: "Is this really happening?"; "Becoming a reality"; "A life of struggle"; and "Brushing oneself off and moving on." Findings suggested a process of moving from uncertainty towards confirmation of one's diagnostic label. Being reclassified with SPMS served as a turning point for many, and was accompanied by a range of cognitive, emotional and behavioral responses. The value of adequate information and support surrounding the transition, and the potential benefit of education and support for health professionals in relation to the transition were indicated. Understanding pwMS' experiences of the transition is essential if clinicians are to provide pwMS with appropriate support during the transition. Implications for Rehabilitation The timing and delivery of preparatory education for patients about the transition to SPMS should be carefully considered. Sufficient information and follow-up support following the reclassification of SPMS is crucial but sometimes lacking. The importance of sensitive communication of the reclassification of SPMS was highlighted. MS Specialist health professionals may potentially benefit from training and support around communication of the reclassification of SPMS. Given the potential negative psychological impact of the transition, the psychological wellbeing of the patients during the transition to SPMS should be monitored and responded to appropriately.

  19. Brain activity changes in cognitive networks in relapsing-remitting multiple sclerosis - insights from a longitudinal FMRI study.

    Directory of Open Access Journals (Sweden)

    Marisa Loitfelder

    Full Text Available BACKGROUND: Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS, but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology. METHODS: 13 MS patients and 15 healthy controls (HC underwent MRI including fMRI (go/no-go task, neurological and neuropsychological exams at baseline (BL and follow-up (FU; minimum 12, median 20 months. We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA plots served to assess fMRI signal variability. RESULTS: Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance. CONCLUSIONS: Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and

  20. Brain activity changes in cognitive networks in relapsing-remitting multiple sclerosis - insights from a longitudinal FMRI study.

    Science.gov (United States)

    Loitfelder, Marisa; Fazekas, Franz; Koschutnig, Karl; Fuchs, Siegrid; Petrovic, Katja; Ropele, Stefan; Pichler, Alexander; Jehna, Margit; Langkammer, Christian; Schmidt, Reinhold; Neuper, Christa; Enzinger, Christian

    2014-01-01

    Extrapolations from previous cross-sectional fMRI studies suggest cerebral functional changes with progression of Multiple Sclerosis (MS), but longitudinal studies are scarce. We assessed brain activation changes over time in MS patients using a cognitive fMRI paradigm and examined correlations with clinical and cognitive status and brain morphology. 13 MS patients and 15 healthy controls (HC) underwent MRI including fMRI (go/no-go task), neurological and neuropsychological exams at baseline (BL) and follow-up (FU; minimum 12, median 20 months). We assessed estimates of and changes in fMRI activation, total brain and subcortical grey matter volumes, cortical thickness, and T2-lesion load. Bland-Altman (BA) plots served to assess fMRI signal variability. Cognitive and disability levels remained largely stable in the patients. With the fMRI task, both at BL and FU, patients compared to HC showed increased activation in the insular cortex, precuneus, cerebellum, posterior cingulate cortex, and occipital cortex. At BL, patients vs. HC also had lower caudate nucleus, thalamus and putamen volumes. Over time, patients (but not HC) demonstrated fMRI activity increments in the left inferior parietal lobule. These correlated with worse single-digit-modality test (SDMT) performance. BA-plots attested to reproducibility of the fMRI task. In the patients, the right caudate nucleus decreased in volume which again correlated with worsening SDMT performance. Given preserved cognitive performance, the increased activation at BL in the patients may be viewed as largely adaptive. In contrast, the negative correlation with SDMT performance suggests increasing parietal activation over time to be maladaptive. Several areas with purported relevance for cognition showed decreased volumes at BL and right caudate nucleus volume decline correlated with decreasing SDMT performance. This highlights the dynamics of functional changes and the strategic importance of specific brain areas for

  1. 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....

  2. Dedicated mobile application for drug adverse reaction reporting by patients with relapsing remitting multiple sclerosis (Vigip-SEP study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Defer, Gilles; Le Caignec, Florian; Fedrizzi, Sophie; Montastruc, François; Chevanne, Damien; Parienti, Jean-Jacques; Peyro-Saint-Paul, Laure

    2018-03-09

    The reporting of adverse drug reactions (ADR) by patients represents an interesting challenge in the field of pharmacovigilance, but the reporting system is not adequately implemented in France. In 2015, only 20 MS patients in France reported ADR due to first-line disease-modifying drugs (DMD), while more than 3000 patients were initiated on DMD. The aim of this study is to validate a proof-of-concept as to whether the use of a mobile application (App) increases ADR reporting among patients with relapsing-remitting multiple sclerosis (RR-MS) receiving DMD. We designed a multi-centric, open cluster-randomized controlled trial, called the Vigip-SEP study (NCT03029897), using the App My eReport France® to report ADR to the appropriate authorities in E2B language, in accordance with European regulations. RR-MS patients who were initiated on, or switched, first-line DMD will be included. In the experimental arm, a neurologist will introduce the patient to the App to report ADR to the appropriate French authorities. In the control arm, the patient will be informed of the existence of the App but will not be introduced to its use and will then report ADR according to the usual reporting procedures. Primary assessment criteria are defined as the average number of ADR per patient and per center. We assume that the App will increase patient reporting by 10-fold. Therefore, we will require 24 centers (12 per arm: 6 MS academic expert centers, 3 general hospitals, 3 private practice neurologists), allowing for an expected enrollment of 180 patients (alpha risk 5%, power 90% and standard deviation 4%). Increasing patient reporting of ADR in a real-life setting is extremely important for therapeutic management of RR-MS, particularly for monitoring newly approved DMD to gain better knowledge of their safety profiles. To increase patient involvement, teaching patients to use tools, such as mobile applications, should be encouraged, and these tools should be tested rigorously

  3. Spasticity improvement in patients with relapsing-remitting multiple sclerosis switching from interferon-β to glatiramer acetate: the Escala Study.

    Science.gov (United States)

    Meca-Lallana, J E; Balseiro, J J; Lacruz, F; Guijarro, C; Sanchez, O; Cano, A; Costa-Frossard, L; Hernández-Clares, R; Sanchez-de la Rosa, R

    2012-04-15

    A recent pilot study suggested spasticity improvement during glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who previously received interferon-β (IFN-β). To evaluate changes in spasticity in MS patients switching from IFN-β to GA. Observational, multicentre study in patients with relapsing-remitting MS (RRMS) and spasticity switching from IFN-β to GA. The primary endpoint comprised changes on Penn Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA. Sixty-eight evaluable patients were included (mean age,41.7±9.5 years; female,70.6%; mean time from MS diagnosis to starting GA,7.6±5.7 years). Previous treatments were subcutaneous IFN-β1a in 42.6% patients, intramuscular IFN-β1a in 41.2% and IFN-β1b in 32.4%, whose mean durations were 3.5±3.3, 2.7±2.5 and 4.4±3.6 years, respectively. Statistically significant reductions in mean scores on all spasticity measurements were observed from baseline to month 3 (PSFS, 1.7±0.9 vs 1.4±0.6, p<0.01; MAS, 0.7±0.5 vs 0.6±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.7±0.8, p<0.01; ATRS, 1.6±0.6 vs 1.4±0.6, p<0.01; GPS, 29.4±22.1 vs 24.7±19.4, p<0.01) and from baseline to month 6 (PSFS, 1.7±0.9 vs 1.3±0.6, p<0.01; MAS, 0.7±0.5 vs 0.5±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.5±0.9, p<0.01; ATRS, 1.6±0.6 vs 1.3±0.6, p<0.01; GPS, 29.4±22.1 vs 19.1±14.8, p<0.01). Spasticity improvement in terms of spasm frequency, muscle tone and pain can be noted after three months and prolonged for six months of GA treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Guillaume Bonnier

    2017-09-01

    Full Text Available ObjectiveQuantitative and semi-quantitative MRI (qMRI metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration, and repair. Moreover, advanced magnetic resonance imaging (MRI metrics with overlapping elements amplify the true tissue-related information and limit measurement noise. In this work, we combined multiple advanced MRI parameters to assess focal and diffuse brain changes over 2 years in a group of early-stage relapsing-remitting MS patients.MethodsThirty relapsing-remitting MS patients with less than 5 years disease duration and nine healthy subjects underwent 3T MRI at baseline and after 2 years including T1, T2, T2* relaxometry, and magnetization transfer imaging. To assess longitudinal changes in normal-appearing (NA tissue and lesions, we used analyses of variance and Bonferroni correction for multiple comparisons. Multivariate linear regression was used to assess the correlation between clinical outcome and multiparametric MRI changes in lesions and NA tissue.ResultsIn patients, we measured a significant longitudinal decrease of mean T2 relaxation times in NA white matter (p = 0.005 and a decrease of T1 relaxation times in the pallidum (p < 0.05, which are compatible with edema reabsorption and/or iron deposition. No longitudinal changes in qMRI metrics were observed in controls. In MS lesions, we measured a decrease in T1 relaxation time (p-value < 2.2e−16 and a significant increase in MTR (p-value < 1e−6, suggesting repair mechanisms, such as remyelination, increased axonal density, and/or a gliosis. Last, the evolution of advanced MRI metrics—and not changes in lesions or brain volume—were correlated to motor and cognitive tests scores evolution (Adj-R2 > 0.4, p < 0.05. In summary, the combination of multiple advanced MRI provided evidence of changes compatible with focal and diffuse brain repair at

  5. 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.

  6. RESULTS OF AN OPEN-LABEL COMPARATIVE RANDOMIZED CLINICAL TRIAL OF AXOGLATIRAN® FS (F-SINTEZ, RUSSIA EFFICIENCY AND SAFETY IN COMPARISON WITH COPAXONE®-TEVA (TEVA PHARMACEUTICAL INDUSTRIES LTD., ISRAEL IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    F. A. Khabirov

    2016-01-01

    Full Text Available Objective. Comparison of Axoglatiran® FS (F-Sintez,  Russia and Copaxone®-Teva (Teva Pharmaceutical Industries Ltd.,  Israel efficiency and safety in patients with relapsing-remitting multiple sclerosis. Materials and methods. In the study 150 patients with relapsing-remitting multiple sclerosis were randomized into 2 groups: patients in the 1st group (n = 100 received treatment with Axoglatiran® FS, patients in the 2nd group (n = 50 received treatment with Copaxone®-Teva. Vital signs of every patient in the study were monitored accompanied by physical examinations, neurological examinations with EDSS (Expanded Disability Status Scale and MSFC (Multiple Sclerosis Functional Composite evaluations, magnetic resonance imaging of the brain and lab tests. Results. Mean age (M ± SD of the patients in the 1st group was 32.8 ± 8.7 years (20–54  years, percentages of men and women were 34 and 66 % respectively, mean age of multiple sclerosis onset was 27.93 ± 7.72 years (11–48 years. Median (Me, lower and upper quartiles estimates [LQ; UQ] on the EDSS scale were 2 [1.5; 3.0] steps (1.0–4.5  steps. In the 2nd group mean age of the patients was 35.2 ± 9.5 years (18–57  years, percentages of men and women were 24 and 76 % respectively, mean age of multiple sclerosis onset was 26.5 ± 6.9 years (18–47  years, EDSS estimates were 2.25 [1.5; 3.5] steps (1–5  steps. In the 1st group 88 (88 % patients completed the study, in the 2nd  group 44 (88 % patients completed the study. Among them in 73 (82.95 % patients in the 1st group and 34 (77.27 % patients in the 2nd  group the disease didn’t exacerbate (p > 0.05. In both groups no progression according to the EDSS and MSFC scale was observed (p > 0.05. Magnetic resonance imaging data showed that dynamics of the total number of T2 lesions, contrast-enhancing T1 lesions, atrophy degree estimated using internuclear index were comparable in both groups (p > 0.05. Safety profiles of

  7. Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-03-15

    To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

  8. The MS@Work study : a 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis

    NARCIS (Netherlands)

    van der Hiele, Karin; van Gorp, Dennis A. M.; Heerings, Marco A. P.; van Lieshout, Irma; Jongen, Peter J.; Reneman, Michiel F.; van der Klink, Jac J. L.; Vosman, Frans; Middelkoop, Huub A. M.; Visser, Leo H.

    2015-01-01

    Background: Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading

  9. The MS@Work study : A 3-year prospective observational study on factors involved with work participation in patients with relapsing-remitting Multiple Sclerosis

    NARCIS (Netherlands)

    van der Hiele, K.; van Gorp, D.A.; Heerings, M.A.; van Lieshout, I.; Jongen, P.J.; Reneman, M.F.; van der Klink, J.J.L.; Vosman, F.; Middelkoop, H.A.; Visser, L.H.

    2015-01-01

    Background Multiple Sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. At this stage in life most people are in the midst of their working career. The majority of MS patients are unable to retain employment within 10 years from disease onset. Leading

  10. Improved self-efficacy in persons with relapsing remitting multiple sclerosis after an intensive social cognitive wellness program with participation of support partners: a 6-months observational study

    NARCIS (Netherlands)

    Jongen, P.J.H.; Ruimschotel, R.; Heerings, M.; Hussaarts, A.; Duyverman, L.; Zande, A. van der; Valkenburg-Vissers, J.; Wolper, H.; Droffelaar, M. van; Lemmens, W.A.J.G.; Donders, R.; Visser, L.H.

    2014-01-01

    BACKGROUND: For persons with multiple sclerosis (MS) it is important to preserve their autonomy, in spite of increasing disability. A major factor mediating autonomy is self-efficacy. According to the social cognitive theory stressors are crucial determinants of self-efficacy, as well as the

  11. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

    KAUST Repository

    Ruhrmann, Sabrina

    2017-08-02

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic and environmental risk factors.We sought to identify DNA methylation changes in CD4+ T cells in patients with relapsing-remitting (RR-MS) and secondary-progressive (SP-MS) disease and healthy controls (HC).We performed DNA methylation analysis in CD4+ T cells from RR-MS, SP-MS, and HC and associated identified changes with the nearby risk allele, smoking, age, and gene expression.We observed significant methylation differences in the VMP1/MIR21 locus, with RR-MS displaying higher methylation compared to SP-MS and HC. VMP1/MIR21 methylation did not correlate with a known MS risk variant in VMP1 or smoking but displayed a significant negative correlation with age and the levels of mature miR-21 in CD4+ T cells. Accordingly, RR-MS displayed lower levels of miR-21 compared to SP-MS, which might reflect differences in age between the groups, and healthy individuals and a significant enrichment of up-regulated miR-21 target genes.Disease-related changes in epigenetic marking of MIR21 in RR-MS lead to differences in miR-21 expression with a consequence on miR-21 target genes.

  12. Quantitative detection of epstein-barr virus DNA in cerebrospinal fluid and blood samples of patients with relapsing-remitting multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Clementina E Cocuzza

    Full Text Available The presence of Epstein-Barr Virus (EBV DNA in cerebrospinal fluid (CSF and peripheral blood (PB samples collected from 55 patients with clinical and radiologically-active relapsing-remitting MS (RRMS and 51 subjects with other neurological diseases was determined using standardized commercially available kits for viral nucleic acid extraction and quantitative EBV DNA detection. Both cell-free and cell-associated CSF and PB fractions were analyzed, to distinguish latent from lytic EBV infection. EBV DNA was detected in 5.5% and 18.2% of cell-free and cell-associated CSF fractions of patients with RRMS as compared to 7.8% and 7.8% of controls; plasma and peripheral blood mononuclear cells (PBMC positivity rates were 7.3% and 47.3% versus 5.8% and 31.4%, respectively. No significant difference in median EBV viral loads of positive samples was found between RRMS and control patients in all tested samples. Absence of statistically significant differences in EBV positivity rates between RRMS and control patients, despite the use of highly sensitive standardized methods, points to the lack of association between EBV and MS disease activity.

  13. Reduction in Healthcare and Societal Resource Utilization Associated with Cladribine Tablets in Patients with Relapsing-Remitting Multiple Sclerosis: Analysis of Economic Data from the CLARITY Study

    DEFF Research Database (Denmark)

    Ali, Shehzad; Paracha, Noman; Cook, Stuart

    2012-01-01

    and home visits during each study period. Societal resource use and productivity outcomes included mean number of hours and days of paid assistance, mean patient and carer work days missed, and self-reported productivity. Results: The mean number of hospital days per patient over 96 weeks was lower...... gadolinium-enhancing (Gd+) lesion (n = 413); and ≥2 relapses in the previous year plus ≥1 T1 Gd+ lesion (n = 138). Cladribine tablets were administered in two (3.5 mg/kg group) or four (5.25 mg/kg group) short courses given at 4-week intervals at the start of a 48-week treatment period, followed by another...... burden. Objective: This study aimed to compare health and societal resource use and productivity in patients with relapsing-remitting MS (RRMS) receiving cladribine tablets versus placebo over 96 weeks in the CLARITY study. Methods: The CLARITY study was a 96-week, randomized, double-blind, placebo...

  14. Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis

    DEFF Research Database (Denmark)

    Knudsen, S; Jennum, P J; Korsholm, K

    2008-01-01

    There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system....../ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI....

  15. Increased cerebrospinal fluid albumin and immunoglobulin A fractions forecast cortical atrophy and longitudinal functional deterioration in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Kroth, Julia; Ciolac, Dumitru; Fleischer, Vinzenz; Koirala, Nabin; Krämer, Julia; Muthuraman, Muthuraman; Luessi, Felix; Bittner, Stefan; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Meuth, Sven G; Groppa, Sergiu

    2017-12-01

    Currently, no unequivocal predictors of disease evolution exist in patients with multiple sclerosis (MS). Cortical atrophy measurements are, however, closely associated with cumulative disability. Here, we aim to forecast longitudinal magnetic resonance imaging (MRI)-driven cortical atrophy and clinical disability from cerebrospinal fluid (CSF) markers. We analyzed CSF fractions of albumin and immunoglobulins (Ig) A, G, and M and their CSF to serum quotients. Widespread atrophy was highly associated with increased baseline CSF concentrations and quotients of albumin and IgA. Patients with increased CSF IgA and CSF IgM showed higher functional disability at follow-up. CSF markers of blood-brain barrier integrity and specific immune response forecast emerging gray matter pathology and disease progression in MS.

  16. Efficacy of a Computer-Assisted Cognitive Rehabilitation Intervention in Relapsing-Remitting Multiple Sclerosis Patients: A Multicenter Randomized Controlled Trial

    Science.gov (United States)

    Kosmidis, Mary H.; Zampakis, Petros; Malefaki, Sonia; Ntoskou, Katerina; Nousia, Anastasia; Bakirtzis, Christos; Papathanasopoulos, Panagiotis

    2017-01-01

    Cognitive impairment is frequently encountered in multiple sclerosis (MS) affecting between 40–65% of individuals, irrespective of disease duration and severity of physical disability. In the present multicenter randomized controlled trial, fifty-eight clinically stable RRMS patients with mild to moderate cognitive impairment and relatively low disability status were randomized to receive either computer-assisted (RehaCom) functional cognitive training with an emphasis on episodic memory, information processing speed/attention, and executive functions for 10 weeks (IG; n = 32) or standard clinical care (CG; n = 26). Outcome measures included a flexible comprehensive neuropsychological battery of tests sensitive to MS patient deficits and feedback regarding personal benefit gained from the intervention on four verbal questions. Only the IG group showed significant improvements in verbal and visuospatial episodic memory, processing speed/attention, and executive functioning from pre - to postassessment. Moreover, the improvement obtained on attention was retained over 6 months providing evidence on the long-term benefits of this intervention. Group by time interactions revealed significant improvements in composite cognitive domain scores in the IG relative to the demographically and clinically matched CG for verbal episodic memory, processing speed, verbal fluency, and attention. Treated patients rated the intervention positively and were more confident about their cognitive abilities following treatment. PMID:29463950

  17. Intensive social cognitive treatment (can do treatment) with participation of support partners in persons with relapsing remitting multiple sclerosis: observation of improved self-efficacy, quality of life, anxiety and depression 1 year later.

    Science.gov (United States)

    Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Duyverman, Lotte; van der Zande, Anneke; Valkenburg-Vissers, Joyce; van Droffelaar, Maarten; Lemmens, Wim; Donders, Rogier; Visser, Leo H

    2016-07-29

    In persons with multiple sclerosis (MS) self-efficacy positively affects health-related quality of life (HRQoL) and physical activity. In a previous study we observed that 6 months after an intensive 3-day social cognitive treatment (Can Do treatment) with the participation of support partners, self-efficacy and HRQoL had improved in persons with relapsing remitting MS (RRMS). Given the chronic nature of the disease, it is important to know whether these beneficial changes may last. Can Do treatment was given to 60 persons with MS and their support partners. At baseline and 12 months after treatment self-efficacy control, self-efficacy function, physical and mental HRQoL, anxiety, depression and fatigue were assessed via self-report questionnaires. Differences were tested via a paired t test. Of the 57 persons with MS that completed the baseline assessment and the 3-day treatment, 38 filled in the 12th month questionnaires (response rate 66.7 %), 22 with RRMS and 14 with progressive MS. In the RR group self-efficacy control had increased by 20.2 % and physical HRQoL by 15.0 %, and depression and anxiety had decreased by 29.8 and 25.9 %, respectively (all P treatment (Can Do treatment) with the participation of support partners may have long lasting beneficial effects on the self-efficacy and HRQoL in persons with RRMS; and that improvements in anxiety and depression, not seen in the 6-month study, may yet develop at 12 months.

  18. Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: study protocol for a cluster randomised controlled trial.

    Science.gov (United States)

    Rahn, Anne Christin; Köpke, Sascha; Kasper, Jürgen; Vettorazzi, Eik; Mühlhauser, Ingrid; Heesen, Christoph

    2015-03-21

    Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilitate participation of individuals in the decision-making process. This cluster randomised controlled trial follows the assumption that decision coaching by trained nurses, using evidence-based patient information and preference elicitation, will facilitate informed choices and induce higher decision quality, as well as better decisional adherence. The decision coaching programme will be evaluated through an evaluator-blinded superiority cluster randomised controlled trial, including 300 patients with suspected or definite relapsing-remitting multiple sclerosis, facing an immunotherapy decision. The clusters are 12 multiple sclerosis outpatient clinics in Germany. Further, the trial will be accompanied by a mixed-methods process evaluation and a cost-effectiveness study. Nurses in the intervention group will be trained in shared decision-making, coaching, and evidence-based patient information principles. Patients who meet the inclusion criteria will receive decision coaching (intervention group) with up to three face-to-face coaching sessions with a trained nurse (decision coach) or counselling as usual (control group). Patients in both groups will be given access to an evidence-based online information tool. The primary outcome is 'informed choice' after six months, assessed with the multi-dimensional measure of informed choice including the sub-dimensions risk knowledge (questionnaire), attitude concerning immunotherapy (questionnaire), and immunotherapy uptake (telephone survey

  19. Iron deposition in the gray matter in patients with relapse-remitting multiple sclerosis: A longitudinal study using three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN)

    International Nuclear Information System (INIS)

    Du, Silin; Sah, Shambhu K.; Zeng, Chun; Wang, Jingjie; Liu, Yi; Xiong, Hua; Li, Yongmei

    2015-01-01

    Purpose: To investigate the relationship between the iron content by magnetic resonance imaging (MRI) and clinic correlation in patients with relapse-remitting multiple sclerosis (RRMS) over a two-year period. Methods: Thirty RRMS patients and 30 healthy control subjects were examined twice, two years apart, by undergoing brain conventional MRI and three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN) sequences at 3.0 T. Quantitative differences in iron content in deep gray matter (GM) nuclei and precentral gyrus GM between patients and control subjects with repeated-measures the mean phase values (MPVs) for ESWAN-filtered phase images. Spearman's rank correlation coefficient analysis was used to evaluate correlations of the MPVs, both 2-year-difference and single-time measurements, to disease duration, expanded disability status scale (EDSS) and times of recurrence. Results: The RRMS patients had higher GM iron concentration than that of the healthy control subjects in both single-time measurements, but only the substantia nigra (SN), and the precentral gyrus GM (PGM) showed a significant statistical difference (p < 0.05). Using the paired samples t test, we found that there were significant differences in two-year-difference measurements of the MPVs in the putamen (PUT), the globus pallidus (GP), the head of the caudate nucleus (HCN), the thalamus (THA), SN, the red nucleus (RN), the dentate nucleus (DN) and PGM, especially in SN (t = 2.92, p = 0.007) in RRMS patients. The MPVs of the PUT, GP, HCN, THA, SN, RN, DN and PGM for the subgroup with RRMS patients in times of recurrence less than twice were similar to the healthy controls. There was no significant difference in all regions of interests (ROIs). However, there were significant differences in all ROIs except THA and GP for the other subgroup with RRMS patients in times of recurrence more than and equal to twice. Spearman's rank correlation coefficient analysis showed there were

  20. Cost-effectiveness of different interferon beta products for relapsing-remitting and secondary progressive multiple sclerosis: Decision analysis based on long-term clinical data and switchable treatments.

    Science.gov (United States)

    Nikfar, Shekoufeh; Kebriaeezadeh, Abbas; Dinarvand, Rassoul; Abdollahi, Mohammad; Sahraian, Mohammad-Ali; Henry, David; Akbari Sari, Ali

    2013-06-22

    Multiple sclerosis (MS) is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000). Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β) and their copied biopharmaceuticals (CBPs) and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs). A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS) in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS). Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS). A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER) of cost/quality adjusted life year (QALY) for all available INF β products (brands, biosimilars and CBPs) were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model. ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($) respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913. The Markov pharmacoeconomics model determined that

  1. Cost-Effectiveness of Different Interferon Beta Products for Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: Decision Analysis Based on Long-Term Clinical Data and Switchable Treatments

    Directory of Open Access Journals (Sweden)

    Shekoufeh Nikfar

    2013-06-01

    Full Text Available Multiple sclerosis (MS is a highly debilitating immune mediated disorder and the second most common cause of neurological disability in young and middle-aged adults. Iran is amongst high MS prevalence countries (50/100,000. Economic burden of MS is a topic of important deliberation in economic evaluations study. Therefore determining of cost-effectiveness interferon beta (INF β and their copied biopharmaceuticals (CBPs and biosimilars products is significant issue for assessment of affordability in Lower-middle-income countries (LMICs.Methods:A literature-based Markov model was developed to assess the cost-effectiveness of three INF βs products compared with placebo for managing a hypothetical cohort of patients diagnosed with relapsing remitting MS (RRMS in Iran from a societal perspective. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS. Disease progression transition probabilities for symptom management and INF β therapies were obtained from natural history studies and multicenter randomized controlled trials and their long term follow up for RRMS and secondary progressive MS (SPMS. A cross sectional study has been developed to evaluate cost and utility. Transitions among health states occurred in 2-years cycles for fifteen cycles and switching to other therapies was allowed. Calculations of costs and utilities were established by attachment of decision trees to the overall model. The incremental cost effectiveness ratio (ICER of cost/quality adjusted life year (QALY for all available INF β products (brands, biosimilars and CBPs were considered. Both costs and utilities were discounted. Sensitivity analyses were done to assess robustness of model.Results:ICER for Avonex, Rebif and Betaferon was 18712, 11832, 15768 US Dollars ($ respectively when utility attained from literature review has been considered. ICER for available CBPs and biosimilars in Iran was $847, $6964 and $11913.Conclusions:The Markov

  2. 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

  3. Iron deposition in the gray matter in patients with relapse-remitting multiple sclerosis: A longitudinal study using three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN)

    Energy Technology Data Exchange (ETDEWEB)

    Du, Silin, E-mail: 182389558@qq.com; Sah, Shambhu K., E-mail: mrsks2007@hotmail.com; Zeng, Chun, E-mail: zengchun19840305@163.com; Wang, Jingjie, E-mail: 345151097@qq.com; Liu, Yi, E-mail: 993537544@qq.com; Xiong, Hua, E-mail: rjdfxyh@163.com; Li, Yongmei, E-mail: lymzhang70@aliyun.com

    2015-07-15

    Purpose: To investigate the relationship between the iron content by magnetic resonance imaging (MRI) and clinic correlation in patients with relapse-remitting multiple sclerosis (RRMS) over a two-year period. Methods: Thirty RRMS patients and 30 healthy control subjects were examined twice, two years apart, by undergoing brain conventional MRI and three-dimensional (3D)-enhanced T2*-weighted angiography (ESWAN) sequences at 3.0 T. Quantitative differences in iron content in deep gray matter (GM) nuclei and precentral gyrus GM between patients and control subjects with repeated-measures the mean phase values (MPVs) for ESWAN-filtered phase images. Spearman's rank correlation coefficient analysis was used to evaluate correlations of the MPVs, both 2-year-difference and single-time measurements, to disease duration, expanded disability status scale (EDSS) and times of recurrence. Results: The RRMS patients had higher GM iron concentration than that of the healthy control subjects in both single-time measurements, but only the substantia nigra (SN), and the precentral gyrus GM (PGM) showed a significant statistical difference (p < 0.05). Using the paired samples t test, we found that there were significant differences in two-year-difference measurements of the MPVs in the putamen (PUT), the globus pallidus (GP), the head of the caudate nucleus (HCN), the thalamus (THA), SN, the red nucleus (RN), the dentate nucleus (DN) and PGM, especially in SN (t = 2.92, p = 0.007) in RRMS patients. The MPVs of the PUT, GP, HCN, THA, SN, RN, DN and PGM for the subgroup with RRMS patients in times of recurrence less than twice were similar to the healthy controls. There was no significant difference in all regions of interests (ROIs). However, there were significant differences in all ROIs except THA and GP for the other subgroup with RRMS patients in times of recurrence more than and equal to twice. Spearman's rank correlation coefficient analysis showed there were

  4. 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.

  5. Immunomodulator therapy migration in relapsing remitting multiple sclerosis: a study of 152 cases Migração medicamentosa de imunomoduladores em esclerose múltipla: estudo em 152 pacientes

    Directory of Open Access Journals (Sweden)

    Sergio Semeraro Jordy

    2008-03-01

    Full Text Available BACKGROUND: Since 1997, immunological modulators have been used for treatment of Relapsing Remitting Multiple Sclerosis (RRMS in the Multiple Sclerosis Attendance and Treatment Center (CATEM with significant alterations in this disease natural history. AIM: To add data on the experience of CATEM for the treatment of RRMS patients that had immunomodulators. METHOD: RRMS patients that received continuously immunomodulator drugs were evaluated on adherence, migration, withdrawal and progression rates. The patients were divided in three groups by the period of immunomodulators intake. RESULTS: There were registered in Group 1 withdrawal in 98 patients (25% and adherence in 292 cases (74%; Group 2 interruption of therapy in 140 patients, 92 (31% due to progression for PSMS, 14 (5% for pregnancy, withdrawal in 34 (11%, adherence in 88%; Group 3 progression in 41 (26%, pregnancy in 3 (2% withdrawal in 42 (27% and adherence in 72%. The migration rate was about one third (31.57% and the principal cause was therapeutic failure; the mean migrating time was 0.5-2.5 years in group 3. CONCLUSION: Immunomodulatory treatment for RRMS patients may have significant levels of failure and side effects; the adherence was compatible with the international literature.INTRODUÇÃO: Na última década foram introduzidos os imunomoduladores para o tratamento da esclerose múltipla (EM forma remitente-recorrente (RR. OBJETIVO: Complementar o relato anterior da experiência de centro brasileiro no acompanhamento dos pacientes em uso dos imunomoduladores. MÉTODO: 390 pacientes que faziam uso de imunomoduladores no Centro de Atendimento à Esclerose Múltipla (CATEM, foram subdivididos por tempo de uso em três grupos, avaliando-se as ocorrências de: abandono, gravidez, conversão da forma RR para secundária progressiva (SP e da aderência. RESULTADOS: No Grupo 1, foram observados abandono do uso de imunomoduladores em 98 pacientes (25% e aderência de 292 casos (74%; no

  6. Hypermethylation of MIR21 in CD4+ T cells from patients with relapsing-remitting multiple sclerosis associates with lower miRNA-21 levels and concomitant up-regulation of its target genes

    KAUST Repository

    Ruhrmann, Sabrina; Ewing, Ewoud; Piket, Eliane; Kular, Lara; Cetrulo Lorenzi, Julio Cesar; Fernandes, Sunjay Jude; Morikawa, Hiromasa; Aeinehband, Shahin; Sayols-Baixeras, Sergi; Aslibekyan, Stella; Absher, Devin M; Arnett, Donna K; Tegner, Jesper; Gomez-Cabrero, David; Piehl, Fredrik; Jagodic, Maja

    2017-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system caused by genetic and environmental factors. DNA methylation, an epigenetic mechanism that controls genome activity, may provide a link between genetic

  7. Evaluator-blinded trial evaluating nurse-led immunotherapy DEcision Coaching In persons with relapsing-remitting Multiple Sclerosis (DECIMS) and accompanying process evaluation: Study protocol for a cluster randomised controlled trial

    OpenAIRE

    Rahn, Anne Christin; Köpke, Sascha; Kasper, Jürgen; Vettorazzi, Eik; Muhlhauser, Ingrid; Heesen, Christoph

    2015-01-01

    Background Multiple sclerosis is a chronic neurological condition usually starting in early adulthood and regularly leading to severe disability. Immunotherapy options are growing in number and complexity, while costs of treatments are high and adherence rates remain low. Therefore, treatment decision-making has become more complex for patients. Structured decision coaching, based on the principles of evidence-based patient information and shared decision-making, has the potential to facilita...

  8. Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Börnsen, Lars; Sellebjerg, Finn

    2016-01-01

    to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize...... the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile...... for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated...

  9. Working memory impairment in multiple sclerosis relapsing-remitting patients with episodic memory deficits Prejuízo de memória operacional em pacientes com esclerose múltipla recorrente-remitente com déficits de memória episódica

    Directory of Open Access Journals (Sweden)

    Simone Freitas Fuso

    2010-04-01

    Full Text Available Episodic memory is impaired in multiple sclerosis (MS patients, possibly because of deficits in working memory (WM functioning. If so, WM alterations should necessarily be found in patients with episodic memory deficits, but this has not yet been demonstrated. In this study we aimed at determining whether episodic memory deficits in relapsing-remitting MS are found in conjunction with impaired WM. We evaluated 32 MS patients and 32 matched healthy controls. Nineteen of the 32 patients had episodic memory impairment, and as a group only these individuals showed deficits in WM capacity, which may lead to difficulty in encoding, and/or retrieving information from episodic memory.Pacientes com esclerose múltipla (EM apresentam prejuízo de memória episódica possivelmente em decorrência de um déficit no funcionamento da memória operacional (MO. Se assim fosse, alterações de MO seriam necessariamente encontradas em pacientes com déficit de memória episódica, mas isto ainda não foi demonstrado. Neste estudo tivemos como objetivo determinar se déficits de memória episódica em pacientes com EM recorrente-remitente são encontrados em associação com prejuízo de MO. Avaliamos 32 pacientes com EM pareados com 32 voluntários saudáveis. Dezenove dos 32 pacientes apresentaram prejuízo de memória episódica, e como grupo, somente estes indivíduos apresentaram déficit na capacidade de MO, o que deve resultar na dificuldade de codificar, e /ou recuperar informações da memória episódica.

  10. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients Contact Us Clinical Fellows ... Relapsing-remitting MS (RRMS) Relapsing-remitting ...

  11. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... for You and Your Practice Publications for Clinicians Publications for Your Patients MS Navigator Program Programs and Services for Your Patients ... Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ...

  12. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... MS Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting ... Here Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the ...

  13. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Relapsing-remitting MS (RRMS) Share this page Facebook Twitter Email Relapsing-remitting MS (RRMS) Relapsing-remitting MS ( ... Start Here Colophon Stay Informed Join Us Facebook Twitter LinkedIn YouTube Pinterest MS Connection About the Society ...

  14. 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

  15. [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...

  16. 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...

  17. 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...

  18. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... without symptoms of which the person is aware. What happens in RRMS? Relapsing-remitting MS is defined ... a different mechanism of action in order to control the disease activity more effectively and help prevent ...

  19. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

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

    Directory of Open Access Journals (Sweden)

    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.

  1. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

    2010-01-01

    Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Become an MS Activist Take Action Current Advocacy Issues Advocacy Results Advocacy News d Raise Awareness d ... MS are more likely to experience gradually worsening problems with walking and mobility, along with whatever other symptoms they may have. Diagnosing relapsing-remitting MS (RRMS) Learn More Learn More ... Room MS Prevalence ...

  3. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... 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 ...

  4. 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

  5. Multiple Sclerosis: Pathogenesis and Treatment

    OpenAIRE

    Loma, Ingrid; Heyman, Rock

    2011-01-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. It affects approximately 400,000 people in the United States and onset is usually during young adulthood. There are four clinical forms of MS, of which relapsing remitting type is the most common. As the etiology of MS is unknown, finding a cure will remain challenging. The main mechanism of injury appears to be inflammation and 8 agents are now FDA approved to help control MS. Th...

  6. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) ...

  7. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Disproved Theories Viruses Clusters d Who Gets MS? Pediatric MS African Americans Hispanics & Latino/as d Multiple ... Questions to Ask d Resources for Specific Populations Pediatric MS Support Veterans with Multiple Sclerosis d Find ...

  8. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Find Support Advanced Care Needs Resources for Specific Populations Find Programs & Services in Your Area Calendar of ... Services: Questions to Ask d Resources for Specific Populations Pediatric MS Support Veterans with Multiple Sclerosis d ...

  9. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (. ... For Professionals Researchers Physicians Nurses Rehabilitation Professionals Mental Health Professionals Health and Wellness Professionals What Is MS? ...

  10. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Viruses Clusters d Who Gets MS? Pediatric MS African Americans Hispanics & Latino/as d Multiple Sclerosis FAQs d ... Diet & Nutrition Exercise Heat & Temperature Sensitivity Sleep Vaccinations Women's Health Unhealthy Habits Managing MS and Another Condition ...

  11. Relapsing-Remitting MS (RRMS)

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    Full Text Available ... Online d Give in Honor or Memory d Workplace Giving d Employer Matching Gifts d Gifts of ... Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (. ...

  12. Epstein-Barr virus and disease activity in multiple sclerosis

    NARCIS (Netherlands)

    D. Buljevac (Dragan); H.Z. Flach (Zwenneke); J. Groen (Jan); P.A. van Doorn (Pieter); F.G.A. van der Meché (Frans); R.Q. Hintzen (Rogier); W.C.J. Hop (Wim); A.D.M.E. Osterhaus (Albert); G.J.J. van Doornum (Gerard)

    2005-01-01

    textabstractOBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study

  13. Will the real multiple sclerosis please stand up?

    NARCIS (Netherlands)

    Stys, P.K.; Zamponi, G.W.; van Minnen, J.; Geurts, J.J.G.

    2012-01-01

    Multiple sclerosis (MS) is considered to be an autoimmune, inflammatory disease of the CNS. In most patients, the disease follows a relapsing - remitting course and is characterized by dynamic inflammatory demyelinating lesions in the CNS. Although on the surface MS may appear consistent with a

  14. Multiple sclerosis or neurological manifestations of Celiac disease

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2013-01-01

    Full Text Available Multiple sclerosis (MS and celiac disease (CD are considered to be T-cell-mediated autoimmune disease. We discuss about a known case of CD-showed relapsing - remitting neurological symptoms compatible with MS. In this rare co-occurrence subject, MS-CD patient, the interaction between MS - and CD-related inflammatory processes is open to discussion.

  15. Menstrually related worsening of symptoms in multiple sclerosis

    NARCIS (Netherlands)

    Zorgdrager, A; DeKeyser, J

    The objective of this study was to investigate whether the menstrual cycle influences multiple sclerosis (MS) symptoms. Seventy-two normally menstruating women (aged 20-50 years) with MS were interviewed. Of the 60 patients with a relapsing-remitting form of MS (RR-MS), 26 (43%) regularly

  16. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) Download Document Pediatric MS Learn More Transverse Myelitis Learn More Neuromyelitis Optica (NMO) Learn More HTLV-I ... Learn More Acute Disseminated Encephalomyelitis (ADEM) Learn More ...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Text Print Discover More Here are a few related topics that may interest you Living with MS (.pdf) Download Brochure Focus on Employment (.pdf) Download Brochure Working with MS (.pdf) Download Brochure Taming Stress (.pdf) Download Brochure Multiple Sclerosis and Your Emotions (. ...

  18. The development of clinical activity in relapsing-remitting MS is associated with a decrease of FasL mRNA and an increase of Fas mRNA in peripheral blood

    NARCIS (Netherlands)

    Lopatinskaya, L.; Boxel van-Dezaire, A.H.H.; Barkhof, F.; Polman, C.H.; Lucas, C.J.; Nagelkerken, L.

    2003-01-01

    In this longitudinal study, we examined the expression of Fas, FasL, CCR3, CCR5 and CXCR3 mRNA in peripheral blood mononuclear cells (PBMCs) of secondary progressive (SP) and relapsing-remitting (RR) multiple sclerosis (MS) patients. In RR patients, FasL, CCR3 and CCR5 mRNA levels were increased

  19. Fluctuations of spontaneous EEG topographies predict disease state in relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Markus Gschwind

    2016-01-01

    In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.

  20. Juxtacortical Lesions and Cortical Thinning in Multiple Sclerosis.

    Science.gov (United States)

    Pareto, D; Sastre-Garriga, J; Auger, C; Vives-Gilabert, Y; Delgado, J; Tintoré, M; Montalban, X; Rovira, A

    2015-12-01

    The role of juxtacortical lesions in brain volume loss in multiple sclerosis has not been fully clarified. The aim of this study was to explore the role of juxtacortical lesions on cortical atrophy and to investigate whether the presence of juxtacortical lesions is related to local cortical thinning in the early stages of MS. A total of 131 patients with clinically isolated syndrome or with relapsing-remitting MS were scanned on a 3T system. Patients with clinically isolated syndrome were classified into 3 groups based on the presence and topography of brain lesions: no lesions (n = 24), only non-juxtacortical lesions (n = 33), and juxtacortical lesions and non-juxtacortical lesions (n = 34). Patients with relapsing-remitting MS were classified into 2 groups: only non-juxtacortical lesions (n = 10) and with non-juxtacortical lesions and juxtacortical lesions (n = 30). A juxtacortical lesion probability map was generated, and cortical thickness was measured by using FreeSurfer. Juxtacortical lesion volume in relapsing-remitting MS was double that of patients with clinically isolated syndrome. The insula showed the highest density of juxtacortical lesions, followed by the temporal, parietal, frontal, and occipital lobes. Patients with relapsing-remitting MS with juxtacortical lesions showed significantly thinner cortices overall and in the parietal and temporal lobes compared with those with clinically isolated syndrome with normal brain MR imaging. The volume of subcortical structures (thalamus, pallidum, putamen, and accumbens) was significantly decreased in relapsing-remitting MS with juxtacortical lesions compared with clinically isolated syndrome with normal brain MR imaging. The spatial distribution of juxtacortical lesions was not found to overlap with areas of cortical thinning. Cortical thinning and subcortical gray matter volume loss in patients with a clinically isolated syndrome or relapsing-remitting MS was related to the presence of juxtacortical

  1. Relapsing/remitting type 1 diabetes

    NARCIS (Netherlands)

    van Megen, Kayleigh M.; Spindler, Matthew P.; Keij, Fleur M.; Bosch, Ineke; Sprangers, Fleur; van Royen-Kerkhof, Annet; Nikolic, Tatjana; Roep, Bart O.

    2017-01-01

    Aims/hypothesis: Type 1 diabetes is believed to be an autoimmune disease associated with irreversible loss of insulin secretory function that follows a chronic progressive course. However, it has been speculated that relapsing/remitting disease progression may occur in type 1 diabetes. Methods: We

  2. Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis

    NARCIS (Netherlands)

    Ramsaransing, GSM; Heersema, DJ; De Keyser, J

    The majority of patients with multiple sclerosis (MS) experience gradual progression of disability, either as secondary progressive MS (SPMS) or primary progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign course with little or no disease progression and minimal disability

  3. 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....

  4. 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

  5. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Bates, David; Edan, Gilles

    2011-01-01

    Natalizumab, a highly specific a4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very...

  6. Tumor necrosis factor alpha gene polymorphism in multiple sclerosis and optic neuritis

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Sandberg-Wollheim, M

    1990-01-01

    The NcoI tumor necrosis factor (TNF alpha) polymorphism was studied in relapsing/remitting multiple sclerosis and monosymptomatic optic neuritis. The frequency of the NcoI marker phenotypes did not differ between healthy controls and the two disease groups. No extra or missing DNA fragments were...

  7. Predicting and preventing the future: actively managing multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Relapsing-remitting multiple sclerosis (MS) has a highly variable clinical course but a number of demographic, clinical and MRI features can guide the clinician in the assessment of disease activity and likely disability outcome. It is also clear that the inflammatory activity in the first five years of relapsing-remitting MS results in the neurodegenerative changes seen in secondary progressive MS 10-15 years later. While conventional first-line disease modifying therapy has an effect on relapses, about one third of patients have a suboptimal response to treatment. With the advent of highly active second-line therapies with their evident marked suppression of inflammation, the clinician now has the tools to manage the course of relapsing-remitting MS more effectively. The development of treatment optimisation recommendations based on the clinical response to first-line therapies can guide the neurologist in more active management of the early course of relapsing-remitting MS, with the aim of preventing both acute inflammatory axonal injury and the neurodegenerative process which leads to secondary progressive MS.

  8. The potential role for ocrelizumab in the treatment of multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Blinkenberg, Morten

    2016-01-01

    B cells play a central role in the pathogenesis in multiple sclerosis (MS), being involved in the activation of proinflammatory T cells, secretion of proinflammatory cytokines, and production of autoantibodies directed against myelin. Hence, the usage of B-cell-depleting monoclonal antibodies....... Other anti-CD20 monoclonal antibodies have been tested as treatments for MS, including ofatumumab that has shown beneficial results in placebo-controlled phase II trials in patients with relapsing-remitting MS. Ocrelizumab is now in phase III development for the treatment of relapsing-remitting MS...

  9. Cortical N-acetyl aspartate is a predictor of long-term clinical disability in multiple sclerosis

    DEFF Research Database (Denmark)

    Wu, Xingchen; Hanson, Lars G.; Skimminge, Arnold Jesper Møller

    2014-01-01

    Objective: To evaluate the prognostic value of the cortical N-acetyl aspartate to creatine ratio (NAA/Cr) in early relapsing-remitting multiple sclerosis (RRMS). Methods: Sixteen patients with newly diagnosed RRMS were studied by serial MRI and MR spectroscopic imaging (MRSI) once every 6 months ...

  10. Bimonthly assessment of magnetization transfer magnetic resonance imaging parameters in multiple sclerosis: a 14-month, multicentre, follow-up study

    NARCIS (Netherlands)

    Mesaros, S.; Rocca, M.A.; Sormani, M.P.; Valsasina, P.; Markowitz, C.; De Stefano, N.; Montalban, X.; Barkhof, F.; Ranjeva, J.P.; Sailer, M.; Kappos, L.; Comi, G.; Filippi, M.

    2010-01-01

    This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing-remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion

  11. 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....

  12. Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis Determinação dos níveis de ICAM-1 e TNFalfaR solúvel no líquido cefalorraqueano e soro numa população de pacientes brasileiros com esclerose múltipla forma surto-remissão

    Directory of Open Access Journals (Sweden)

    Soniza Vieira Alves-Leon

    2001-03-01

    Full Text Available Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS, a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF and serum levels of soluble intercellular adhesion molecule (ICAM-1 and TNFalphaR (60kD from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (pCitocinas e moléculas de adesão estão implicadas na patogênese da esclerose múltipla (EM, uma doença inflamatória crônica do sistema nervoso central. Neste estudo, nós determinamos os níveis solúveis da molécula de adesão intercelular (sICAM-1 e TNFalfaR (60kD no soro e líquido cefalorraqueano (LCR de 20 pacientes com EM clinicamente definida durante surto ou remissão. Os pacientes com EM apresentaram, em comparação com os grupos controle formados por indivíduos sadios e com hérnia de disco intervertebral submetidos a mielografia, níveis significativamente (p< 0.001 elevados de sICAM-1 e TNFalfaR tanto no soro como no LCR. Independente do estágio da doença, nenhuma diferença significativa foi encontrada entre os pacientes durante o surto (657±124.9 ng/ml ou na remissão (627±36.2 ng/ml. Um aumento consistente dos níveis de TNFalfaR no soro e LCR, apontam para a existência de processo inflamatório continuado no tecido cerebral dos pacientes com EM, a despeito da ausência de sinais clínicos de doença em atividade.

  13. 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.

  14. 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.

  15. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis

    DEFF Research Database (Denmark)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Fredriksen, Jette Lautrup

    2016-01-01

    Background Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis...... associated with Interferon-beta treatment. Case presentation We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved...... Interferon-beta-1-alpha therapy in patients with multiple sclerosis....

  16. Spatial Correlation of Pathology and Perfusion Changes within the Cortex and White Matter in Multiple Sclerosis.

    Science.gov (United States)

    Mulholland, A D; Vitorino, R; Hojjat, S-P; Ma, A Y; Zhang, L; Lee, L; Carroll, T J; Cantrell, C G; Figley, C R; Aviv, R I

    2018-01-01

    The spatial correlation between WM and cortical GM disease in multiple sclerosis is controversial and has not been previously assessed with perfusion MR imaging. We sought to determine the nature of association between lobar WM, cortical GM, volume and perfusion. Nineteen individuals with secondary-progressive multiple sclerosis, 19 with relapsing-remitting multiple sclerosis, and 19 age-matched healthy controls were recruited. Quantitative MR perfusion imaging was used to derive CBF, CBV, and MTT within cortical GM, WM, and T2-hyperintense lesions. A 2-step multivariate linear regression (corrected for age, disease duration, and Expanded Disability Status Scale) was used to assess correlations between perfusion and volume measures in global and lobar normal-appearing WM, cortical GM, and T2-hyperintense lesions. The Bonferroni adjustment was applied as appropriate. Global cortical GM and WM volume was significantly reduced for each group comparison, except cortical GM volume of those with relapsing-remitting multiple sclerosis versus controls. Global and lobar cortical GM CBF and CBV were reduced in secondary-progressive multiple sclerosis compared with other groups but not for relapsing-remitting multiple sclerosis versus controls. Global and lobar WM CBF and CBV were not significantly different across groups. The distribution of lobar cortical GM and WM volume reduction was disparate, except for the occipital lobes in patients with secondary-progressive multiple sclerosis versus those with relapsing-remitting multiple sclerosis. Moderate associations were identified between lobar cortical GM and lobar normal-appearing WM volume in controls and in the left temporal lobe in relapsing-remitting multiple sclerosis. No significant associations occurred between cortical GM and WM perfusion or volume. Strong correlations were observed between cortical-GM perfusion, normal appearing WM and lesional perfusion, with respect to each global and lobar region within HC, and

  17. 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 ...

  18. Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

    Science.gov (United States)

    Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

    2016-01-01

    Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

  19. Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis.

    Directory of Open Access Journals (Sweden)

    Hanni S M Kiiski

    Full Text Available Conduction along the optic nerve is often slowed in multiple sclerosis (MS. This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis.

  20. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring

    DEFF Research Database (Denmark)

    Kappos, Ludwig; Bates, David; Edan, Gilles

    2011-01-01

    Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very......, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.......Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very...... active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS...

  1. Safety and Efficacy of Fingolimod in Treatment-Naïve Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    James J. Marriott

    2011-01-01

    Full Text Available Fingolimod was recently approved for use in the United States after two phase III trials confirmed its effectiveness in reducing disease activity in relapsing-remitting multiple sclerosis. These positive results, coupled with the important fact that this is the first oral disease-modifying therapy, has lead to considerable enthusiasm amongst physicians and patients. However, fingolimod is associated with rare but serious adverse events. In addition, unlike conventional disease-modifying therapies, cardiopulmonary, ophthalmological and dermatological safety monitoring unfamiliar to both neurologists and patients is required before and during treatment. This paper will discuss these issues from the perspective of using fingolimod as a first-line disease-modifying therapy in treatment-Naïve relapsing-remitting multiple sclerosis patients

  2. Comparison effectiveness of Dialectic Behavioral Therapy and Behavior Cognitive Therapy on Depression in the Multiple sclerosis

    OpenAIRE

    Narges Zamani; Mehran Farhadi; Hosein Jenaabadi

    2017-01-01

    Balsimelli S, Mendes MF, Bertolucci PH, Tilbery CP. Attention impairment associated with relapsing-remitting multiple sclerosis patients with mild incapacity. Arq Neuropsiquiatr 2007;65(2A):262-7. Zamani N, Ahmadi V, Ataie Moghanloo V, Mirshekar S. Comparing the effectiveness of two therapeutic methods of dialectical behavior therapy and cognitive behavior therapy on the improvement of impulsive behavior in the patients suffering  from major depressive disorder (MDD) showing a t...

  3. Investigation of autoantibody profiles for cerebrospinal fluid biomarker discovery in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Beyer, Natascha Helena; Lueking, Angelika; Kowald, Axel

    2012-01-01

    Using the UNIarray® marker technology platform, cerebrospinal fluid immunoglobulin G reactivities of 15 controls and 17 RRMS patients against human recombinant proteins were investigated. Patient cerebrospinal fluids were oligoclonal band positive and reactivities were compared to that of sex...

  4. Guided Imagery Improves Mood, Fatigue, and Quality of Life in Individuals With Multiple Sclerosis: An Exploratory Efficacy Trial of Healing Light Guided Imagery.

    Science.gov (United States)

    Case, Laura K; Jackson, Paula; Kinkel, Revere; Mills, Paul J

    2018-01-01

    Multiple sclerosis is a disabling and progressive neurological disease that has significant negative effects on health-related quality of life. This exploratory efficacy study examined the effects of Healing Light Guided Imagery (HLGI), a novel variant of guided imagery, compared with a wait-list control in patients with relapsing-remitting multiple sclerosis. Changes in the Beck Depression Inventory, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life instrument (physical and mental components) were compared between groups. Patients who completed HLGI (N = 9) showed significant reductions in depressed mood ( P mental ( P journaling (N = 8). Our results suggest that HLGI can improve self-reported physical and mental well-being in patients with relapsing-remitting multiple sclerosis. Further research is needed to study the effectiveness of this therapy, as well as its mind-body mechanisms of action.

  5. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Comi, G; Martinelli, V; Rodegher, M

    2009-01-01

    treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel Udgivelsesdato: 2009/10/31......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

  6. 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.

  7. 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.

  8. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Comi, G; Martinelli, V; Rodegher, M

    2009-01-01

    BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis....... treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.......BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...

  9. 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

  10. Multiple sclerosis

    International Nuclear Information System (INIS)

    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

  11. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability.

    Science.gov (United States)

    Scalfari, Antonio; Neuhaus, Anneke; Degenhardt, Alexandra; Rice, George P; Muraro, Paolo A; Daumer, Martin; Ebers, George C

    2010-07-01

    The relationship of relapses to long-term disability in multiple sclerosis is uncertain. Relapse reduction is a common therapeutic target but clinical trials have shown dissociation between relapse suppression and disability accumulation. We investigated relationships between relapses and disability progression for outcomes of requiring assistance to walk, being bedridden and dying from multiple sclerosis [Disability Status Scale 6, 8, 10] by analysing 28 000 patient-years of evolution in 806-bout onset patients from the London Ontario natural history cohort. Having previously shown no effect of relapse frequency among progressive multiple sclerosis subtypes, here we examined these measures in the pre-progressive or relapsing-remitting phase. Survival was compared among groups stratified by (i) early relapses--number of attacks during the first 2 years of multiple sclerosis; (ii) length of first inter-attack interval; (iii) interval between onset and Disability Status Scale 3 (moderate disability); (iv) number of attacks from the third year of disease up to onset of progression; and (v) during the entire relapsing-remitting phase. Early clinical features can predict hard disability outcomes. Frequent relapses in the first 2 years and shorter first inter-attack intervals predicted shorter times to reach hard disability endpoints. Attack frequencies, in the first 2 years, of 1 versus >or=3, gave differences of 7.6, 12.8 and 20.3 years in times from disease onset to Disability Status Scale 6, 8 and 10, respectively. Time to Disability Status Scale 3 highly and independently predicted time to Disability Status Scale 6, 8 and 10. In contrast, neither total number of relapsing-remitting phase attacks nor of relapses experienced during the relapsing-remitting phase after the second year up to onset of progression showed a deleterious effect on times from disease onset, from progression onset and from Disability Status Scale 3 to these hard endpoints. The failure of a

  12. Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis

    DEFF Research Database (Denmark)

    Martinez-Lapiscina, Elena H; Arnow, Sam; Wilson, James A

    2016-01-01

    of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. METHODS: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis...... with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. FINDINGS: 879 patients with clinically isolated syndrome...

  13. [Oral treatments in multiple sclerosis].

    Science.gov (United States)

    Meca-Lallana, José Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

    2014-12-01

    The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Natalizumab therapy of multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Multiple sclerosis (MS) is the commonest disabling neurological disease of young and middle-aged adults affecting 1 million persons world wide. The illness begins with a relapsing-remitting MS course in 85%-90% of patients; the other 10%-15% have a primary progressive onset MS. Our current understanding is that MS is an autoimmune disorder with an inflammatory T-cell attack on myelin or some component of the oligodendrocyte--myelin structure. Relapses of disease activity result in plaques of demyelination with destruction of myelin and, to a lesser, extent axons. Lymphocytes within the central nervous system tissue recruit more cells leading to an inflammatory cascade that causes myelin damage, axonal disruption, and neuronal death. If the plaque occurs in a vocal area of the central nervous system then symptoms relating to that area result. However, magnetic resonance imaging shows that approximately 10 times more lesions occur in asymptomatic areas of the brain. Recovery from an initial relapse may appear relatively complete but persistent inflammation results in axonal injury and residual disability results. With time and accumulated lesion load, secondary degeneration of denuded axons results in the phase of secondary progressive MS usually 15-20 years after onset.

  15. Pediatric multiple sclerosis in Venezuela

    Directory of Open Access Journals (Sweden)

    Joaquín A. Peña

    2012-04-01

    Full Text Available OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS. METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%, brainstem/cerebellum and spinal cord affectation (27.6%, headache (26%. Less frequent symptoms were sensory symptoms (8% and optic neuritis (7%. DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela.

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

    Directory of Open Access Journals (Sweden)

    Manuel Vázquez-Marrufo

    Full Text Available BACKGROUND: 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. RESULTS: 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 (p<0.05. ANOVAs showed for the patient group a significant latency delay for P1 and N1 components (p<0.05 and a decrease of P3 amplitude for congruent and incongruent stimuli (p<0.01. With regard to correlation analysis, PASAT-3s and SDMT showed significant correlations with behavioral measures of the Attention Network Test (p<0.01 and an ERP parameter (CNV amplitude. CONCLUSIONS: Behavioral data are highly correlated with the neuropsychological scores and show that the alerting and orienting mechanisms in the patient group were impaired. Reduced amplitude for the Contingent Negative Variation in the patient group suggests that this component could be a physiological marker related to the alerting and orienting impairment in relapsing-remitting multiple 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

  17. 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 ...

  18. Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Kaspar-Josche Streitberger

    Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

  19. 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.

  20. 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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

  5. 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.

  6. Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

    Science.gov (United States)

    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.

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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…

  13. 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)

  14. Rhabdomyolysis following interferon-beta treatment in a patient with multiple sclerosis - A case report.

    Science.gov (United States)

    Dalbjerg, Sara Maria; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2016-07-01

    Multiple sclerosis is an inflammatory disease of the central nervous system for which there is currently no cure. Interferon-beta-1-alpha is worldwide one of the most widely used treatments in multiple sclerosis. To our knowledge there is one previous reported case of rhabdomyolysis associated with Interferon-beta treatment. We describe a 30 year old man with relapsing remitting multiple sclerosis who developed rhabdomyolysis and increased creatine kinase following Interferon-beta-1-alpha therapy. After the medication was discontinued, the patient rapidly improved. Clinicians should be aware of the possibility of rhabdomyolysis occurring during Interferon-beta-1-alpha therapy. In cases where patients complain of severe myalgia, and in particular if weakness is reported, creatine kinase activity should be measured to prevent irreversible rhabdomyolysis during Interferon-beta-1-alpha therapy in patients with multiple sclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Neuroactive steroid levels in plasma and cerebrospinal fluid of male multiple sclerosis patients.

    Science.gov (United States)

    Caruso, Donatella; Melis, Marta; Fenu, Giuseppe; Giatti, Silvia; Romano, Simone; Grimoldi, Maria; Crippa, Donatella; Marrosu, Maria Giovanna; Cavaletti, Guido; Melcangi, Roberto Cosimo

    2014-08-01

    Neuroactive steroid family includes molecules synthesized in peripheral glands (i.e., hormonal steroids) and directly in the nervous system (i.e., neurosteroids) which are key regulators of the nervous function. As already reported in clinical and experimental studies, neurodegenerative diseases affect the levels of neuroactive steroids. However, a careful analysis comparing the levels of these molecules in cerebrospinal fluid (CSF) and in plasma of multiple sclerosis (MS) patients is still missing. To this aim, the levels of neuroactive steroids were evaluated by liquid chromatography-tandem mass spectrometry in CSF and plasma of male adults affected by Relapsing-Remitting MS and compared with those collected in control patients. An increase in pregnenolone and isopregnanolone levels associated with a decrease in progesterone metabolites, dihydroprogesterone, and tetrahydroprogesterone was observed in CSF of MS patients. Moreover, an increase of 5α-androstane-3α,17β-diol and of 17β-estradiol levels associated with a decrease of dihydrotestosterone also occurred. In plasma, an increase in pregnenolone, progesterone, and dihydrotestosterone and a decrease in dihydroprogesterone and tetrahydroprogesterone levels were reported. This study shows for the first time that the levels of several neuroactive steroids, and particularly those of progesterone and testosterone metabolites, are deeply affected in CSF of relapsing-remitting MS male patients. We here demonstrated that, the cerebrospinal fluid and plasma levels of several neuroactive steroids are modified in relapsing remitting multiple sclerosis male patients. Interestingly, we reported for the first time that, the levels of progesterone and testosterone metabolites are deeply affected in cerebrospinal fluid. These findings may have an important relevance in therapeutic and/or diagnostic field of multiple sclerosis. © 2014 International Society for Neurochemistry.

  16. 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)

  17. 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

  18. Nutrition Facts in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Paolo Riccio

    2015-02-01

    Full Text Available The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.

  19. CLIPPERS-like MRI findings in a patient with multiple sclerosis.

    Science.gov (United States)

    Ferreira, R M; Machado, G; Souza, A S; Lin, K; Corrêa-Neto, Y

    2013-04-15

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) has been described as a clinically and radiologically distinct pontine-predominant encephalomyelitis with a favorable response to high dose corticosteroids and usually requiring chronic immunosuppresive therapy. Brain magnetic resonance imaging (MRI) reveals a characteristic pattern of punctate and curvilinear enhancement lesions in the pons extending variably to surrounding areas. We herein describe such imaging findings in a patient with a definite diagnosis of relapsing-remitting multiple sclerosis (MS). Copyright © 2013 Elsevier B.V. All rights reserved.

  20. 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...

  1. Pathological Assessment of Brain White Matter in Relapsing-Remitting MS Patients using Quantitative Magnetization Transfer Imaging

    Directory of Open Access Journals (Sweden)

    Khodarahm Pahlevan

    2011-09-01

    Full Text Available Introduction: Multiple sclerosis (MS is characterized by lesions in the white matter (WM of the central nervous system. Magnetic resonance imaging is the most specific and sensitive method for diagnosis of multiple sclerosis. However, the ability of conventional MRI to show histopathologic heterogeneity of MS lesions is insufficient. Quantitative magnetization transfer imaging (qMTI is a relatively new method to investigate pathologic processes of the brain tissue occurring in MS patients. Material and Methods: Voxel-based analyses allow regional comparisons between groups to be made for the whole brain in a single analysis. This is done by coregistering data from all individual subjects to a reference brain, generally referred to as the "standard space", and then comparing them on a voxel-by-voxel basis. This study aimed to analyze whole-brain quantitative T1 maps, not to find global changes or changes in selected regions, but specifically to investigate the spatial distribution throughout the brain of T1 increases in MS WM with respect to control WM. In this study, 11 healthy controls, 10 relapsing-remitting (RR MS patients and 13 CIS patients were studied using MT-MRI imaging. MT parameters, including magnetization transfer ratio (MTR, magnetization transfer rate between free protons and restricted macromolecular protons, Ksat and longitudinal relaxation times (with and without MT saturation pulse, T1sat and T1free values were evaluated. Results: The results showed that, at a group level, there is widespread involvement of WM throughout the brain in CIS MS and especially in RRMS, where a significant T1 increase was found in 15.58% of WM voxels (normals < RR. Discussion and Conclusion: This study demonstrates that WM in large parts of the brain is susceptible to disease processes in RR and CIS MS

  2. Gray Matter Is Targeted in First-Attack Multiple Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao; Schepmoes, Athena A.; Xie, Fang; Bergquist, Jonas P.; Vecsei, Lazlo' ; Zadori, Denes; Camp, David G.; Holland, Bart K.; Smith, Richard D.; Coyle, Patricia K.

    2013-09-10

    The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We found that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.

  3. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  4. 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...

  5. The Combined Quantification and Interpretation of Multiple Quantitative Magnetic Resonance Imaging Metrics Enlightens Longitudinal Changes Compatible with Brain Repair in Relapsing-Remitting Multiple Sclerosis Patients

    NARCIS (Netherlands)

    Bonnier, G.; Marechal, B.; Fartaria, M.J.; Marques, J.P.; Simioni, S.; Schluep, M.; Du Pasquier, R.; Thiran, J.-P.; Krueger, G.; Granziera, C.

    2017-01-01

    Objective: Quantitative and semi-quantitative MRI (qMRI) metrics provide complementary specificity and differential sensitivity to pathological brain changes compatible with brain inflammation, degeneration and repair. Moreover, advanced MRI metrics with overlapping elements amplify the true

  6. Multiple sclerosis and positive lyme serology

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    Marco Aurélio Lana-Peixoto

    1994-12-01

    Full Text Available As Lyme neuroborreliosis (LNB may clinically mimick multiple sclerosis (MS the presence of antibodies to Borrelia burgdorferi in serum of patients with a MS-like disease in non-edemic areas for Lyme disease may be troublesome. We report the case of a 45-year-old white female with the diagnosis of relapsing/ remitting form of MS due to a 15-year history of optic neuritis and recurrent episodes of motor and sensation disturbance in the upper right limb and in both lower extremites associated with bladder dysfunction. A magnetic resonance imaging of the brain revealed multiple high intensity periventricular white matter lesions. The patient had been exposed to ticks but did not recall the presence of erythema migrans. ELISA for Lyme disease was positive in two different laboratories and the positive serology was confirmed by Western blotting. No convincing reponse followed treatment with ceftriaxone. Although it is clear that the patient had been infect by Borrelia burgdorferi the relationship of this spirochetal infection with the neurological disease could not be ascertained.

  7. 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.

  8. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

    Science.gov (United States)

    Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

    2014-11-01

    Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included

  9. [Pegylation and interferons in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Diego Centonze

    2016-07-01

    Full Text Available Pegylation is a procedure used for drug development since the 1970s and consists of the conjugation of a polyethylene glycol molecule (PEG to a drug. PEG has shown to be safe and effective in improving the pharmacokinetic and pharmacodynamic profile of drugs. Recently, a 20 kDa linear chain of PEG was conjugated to interferon beta-1a with the aim to offer a new treatment option to relapsing-remitting multiple sclerosis (RRMS patients. Due to a prolonged bioavailability, this new drug can be administered less frequently (every two weeks than the other interferons beta available, thus allowing to hypothesize a better adherence to the treatment, which, in turn, should result in better clinical and economic outcomes. A phase III clinical trial has proven its effectiveness compared to placebo in RRMS patients, as well as a safety profile comparable to that found in other interferon beta preparations. The immunogenicity of this new molecule is < 1%, thus minimizing the suppression or reduction of interferon beta biological activity that could come from the development of Neutralizing Antibodies (NAbs. [Article in Italian

  10. Effects of Sport Climbing on Multiple Sclerosis

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    Julia Steimer

    2017-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmune and neurodegenerative disease of the central nervous system (CNS with different types of disease courses (relapsing-remitting, secondary-progressive, primary progressive that leads to physical as well as mental disability. The symptoms comprise paresis or/and paralysis, ataxia, bladder dysfunction, visual problems as well as effects on cognition. There is limited data regarding the possible effects of sport climbing respectively therapeutic climbing on patients with MS. Sport climbing offers many potentially beneficial effects for patients with MS since there are effects on coordination, muscular strength, and cognition to name the most relevant ones. Also, disease models in rodents point toward such positive outcomes of climbing. Therefore, we assessed the currently available research literature on general effects of physical exercise, impact of climbing on body and mind and therapeutic climbing for prevention or therapy for the treatment of MS. The sparse published controlled trials that investigated this sport activity on different groups of patients with neurological or geriatric diseases grossly differ in study design and outcome parameters. Nevertheless, it appears that climbing offers the opportunity to improve some of the symptoms of patients with MS and can contribute to an enhanced quality of life.

  11. 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

  12. 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

  13. [Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy

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    Gianluca Furneri

    2016-06-01

    RESULTS: In the base-case analysis, DMF was more efficacious than alternatives, in terms of both survival (19.496 vs. 19.297-19.461 discounted LYs, respectively, and QALYs (6.548 vs. 5.172- 6.212 discounted QALYs, respectively. Per-patient lifetime costs with DMF amounted to € 276,500, similarly to the other options. DMF was the drug with the largest effect of disability cost reduction. DMF was dominant vs. IFN beta-1a 44 mcg and cost-effective vs. all other IFNs, GA and teriflunomide, with incremental cost-effectiveness ratio (ICERs between € 11,272 and € 23,409. All ICER values were lower than the € 50,000 per QALY threshold. One-way sensitivity analysis showed that, for all tested scenarios, ICER of DMF vs. therapeutic alternatives remained favourable (≤ 50.000 €/QALY gained and the results of probabilistic sensitivity analysis showed that the probability for DMF of being favourable (≤ 50.000 €/QALY gained was between around 70% and 93%, thus ensuring robustness of the results. CONCLUSIONS: The results of this economic analysis show that, at the current price and the described assumptions, DMF represents a cost-effective option vs. other available first-line treatments indicated in RRMS in the perspective of the Italian NHS. [Article in Italian

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

    Science.gov (United States)

    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

  15. Corrigendum to ‘Multiple sclerosis: New insights and trends’

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    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.

  16. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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 ...

  19. Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Torrealdea Javier

    2011-07-01

    Full Text Available Abstract Background The relapsing-remitting dynamics is a hallmark of autoimmune diseases such as Multiple Sclerosis (MS. Although current understanding of both cellular and molecular mechanisms involved in the pathogenesis of autoimmune diseases is significant, how their activity generates this prototypical dynamics is not understood yet. In order to gain insight about the mechanisms that drive these relapsing-remitting dynamics, we developed a computational model using such biological knowledge. We hypothesized that the relapsing dynamics in autoimmunity can arise through the failure in the mechanisms controlling cross-regulation between regulatory and effector T cells with the interplay of stochastic events (e.g. failure in central tolerance, activation by pathogens that are able to trigger the immune system. Results The model represents five concepts: central tolerance (T-cell generation by the thymus, T-cell activation, T-cell memory, cross-regulation (negative feedback between regulatory and effector T-cells and tissue damage. We enriched the model with reversible and irreversible tissue damage, which aims to provide a comprehensible link between autoimmune activity and clinical relapses and active lesions in the magnetic resonances studies in patients with Multiple Sclerosis. Our analysis shows that the weakness in this negative feedback between effector and regulatory T-cells, allows the immune system to generate the characteristic relapsing-remitting dynamics of autoimmune diseases, without the need of additional environmental triggers. The simulations show that the timing at which relapses appear is highly unpredictable. We also introduced targeted perturbations into the model that mimicked immunotherapies that modulate effector and regulatory populations. The effects of such therapies happened to be highly dependent on the timing and/or dose, and on the underlying dynamic of the immune system. Conclusion The relapsing dynamic in MS

  20. Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

    Science.gov (United States)

    Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

    2010-01-01

    Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

  1. Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study

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    Gonzalez-Toledo Eduardo

    2007-10-01

    Full Text Available Abstract Background The presence of antiphospholipid antibodies (APLA in multiple sclerosis (MS patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA. Methods A consecutive cohort of 24 subjects with relapsing-remitting (RR MS were studied of whom 7 were in remission (Rem and 17 in exacerbation (Exc. All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL, β2 glycoprotein I (β2GPI, Factor VII/VIIa (FVIIa, phosphatidylcholine (PC, phosphatidylserine (PS and phosphatidylethanolamine (PE. Results In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p Conclusion The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.

  2. Diffusion tensor MR imaging evaluation of the corpus callosum of patients with multiple sclerosis

    International Nuclear Information System (INIS)

    Rueda, Fernanda; Domingues, Romeu Cortes; Papais-Alvarenga, Regina M.; Gasparetto, Emerson L.

    2008-01-01

    Objective: To evaluate the fractional anisotropy (FA) values of the normal-appearing white matter of the corpus callosum (CC) in patients with relapsing-remitting multiple sclerosis (MS). Method: Fifty-seven patients with diagnosis of relapsing-remitting MS and 47 age- and gender-matched controls were studied. A conventional MR imaging protocol and a DTI sequence were performed. One neuro radiologist placed the regions of interest (ROIs) in the FA maps in five different portions of the normal-appearing CC (rostrum, genu, anterior and posterior portion of the body and splenium) in all cases. The statistical analysis was performed with the Mann-Whitney U test and p<0.05 was considered statistically significant. Results: The FA values were lower in the MS patients compared with the controls (p<0.05) in the following CC regions: rostrum (0.720 vs 0.819), anterior body (0.698 vs 0.752), posterior body (0.711 vs 0.759) and splenium (0.720 vs 0.880). Conclusion: In this series, there was a robust decrease in the FA in all regions of the normal-appearing CC, being significant in the rostrum, body and splenium. This finding suggests that there is a subtle and diffuse abnormality in the CC, which could be probably related to myelin content loss, axonal damage and gliosis. (author)

  3. Correlation between white matter damage and gray matter lesions in multiple sclerosis patients

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    Xue-mei Han

    2017-01-01

    Full Text Available We observed the characteristics of white matter fibers and gray matter in multiple sclerosis patients, to identify changes in diffusion tensor imaging fractional anisotropy values following white matter fiber injury. We analyzed the correlation between fractional anisotropy values and changes in whole-brain gray matter volume. The participants included 20 patients with relapsing-remitting multiple sclerosis and 20 healthy volunteers as controls. All subjects underwent head magnetic resonance imaging and diffusion tensor imaging. Our results revealed that fractional anisotropy values decreased and gray matter volumes were reduced in the genu and splenium of corpus callosum, left anterior thalamic radiation, hippocampus, uncinate fasciculus, right corticospinal tract, bilateral cingulate gyri, and inferior longitudinal fasciculus in multiple sclerosis patients. Gray matter volumes were significantly different between the two groups in the right frontal lobe (superior frontal, middle frontal, precentral, and orbital gyri, right parietal lobe (postcentral and inferior parietal gyri, right temporal lobe (caudate nucleus, right occipital lobe (middle occipital gyrus, right insula, right parahippocampal gyrus, and left cingulate gyrus. The voxel sizes of atrophic gray matter positively correlated with fractional anisotropy values in white matter association fibers in the patient group. These findings suggest that white matter fiber bundles are extensively injured in multiple sclerosis patients. The main areas of gray matter atrophy in multiple sclerosis are the frontal lobe, parietal lobe, caudate nucleus, parahippocampal gyrus, and cingulate gyrus. Gray matter atrophy is strongly associated with white matter injury in multiple sclerosis patients, particularly with injury to association fibers.

  4. Frontal parenchymal atrophy measures in multiple sclerosis.

    Science.gov (United States)

    Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

    2004-10-01

    The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: PColor Word Interference test, Pcognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures

  5. Assessment of patients with multiple sclerosis according to tests of the Multiple Sclerosis Functional Composite

    Directory of Open Access Journals (Sweden)

    Anelise Ineu Figueiredo

    Full Text Available Abstract Introduction: The Multiple Sclerosis Functional Composite (MSFC is a scale that evaluates the functional and cognitive aspects of patients with multiple sclerosis (MS. Objective: To compare the performance of individuals with the relapsing-remitting form of MS (RRMS with a group of healthy subjects using the MSFC. Methods: Twenty subjects were investigated in this study, consisting of 10 patients with clinical diagnosis of RRMS and 10 controls with similar gender and age to the group with the disease. The three tests that comprise the MSFC were used for the evaluation of gait, upper limb motor function and cognition (memory and processing speed. Student's t-test was used to assess data with normal distribution and data with skewed distribution were evaluated using the Mann-Whitney test. Results: The results showed that the patients with RRMS took longer to perform the locomotion test (6.91 ± 2.35 compared to the control group (5.16 ± 1.28. The MS group (22.06 ± 5.44 also showed greater difficulty in performing a task with the dominant upper limb compared to the healthy subjects (17.79 ± 2.96. No statistically significant difference was found between the groups in the performance of cognitive tasks (p = .65. Conclusion: The use of the MSFC tests proved valuable for measuring possible motor and cognitive impairments in patients with RRMS. Thus, it is suggested that this scale is adopted in clinical practice, improving therapies for the treatment of MS patients and thereby providing them a better quality of life.

  6. Plasma Biomarkers Discriminate Clinical Forms of Multiple Sclerosis

    Science.gov (United States)

    Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Seyfferth, Ansgar; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Fernández-Paredes, Lidia; Albert, Matthew L.; Sánchez-Ramón, Silvia

    2015-01-01

    Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. PMID:26039252

  7. Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review.

    Science.gov (United States)

    Kalincik, Tomas

    2015-01-01

    Relapses (episodic exacerbations of neurological signs or symptoms) are a defining feature of relapsing-remitting multiple sclerosis (MS), the most prevalent MS phenotype. While their diagnostic value relates predominantly to the definition of clinically definite MS, their prognostic value is determined by their relatively high associated risk of incomplete remission resulting in residual disability. The mechanisms governing a relapse incidence are unknown, but numerous modifiers of relapse risk have been described, including demographic and clinical characteristics, many of which represent opportunities for improved disease management. Also relapse phenotypes have been associated with patient and disease characteristics and an individual predisposition to certain phenotypic presentations may imply individual neuroanatomical disease patterns. While immunomodulatory therapies and corticosteroids represent the mainstay of relapse prevention and acute management, respectively, their effect has only been partial and further search for more efficient relapse therapies is warranted. Other areas of research include pathophysiology and determinants of relapse incidence, recurrence and phenotypes, including the characteristics of the relapsing and non-relapsing multiple sclerosis variants and their responsiveness to therapies. © 2015 S. Karger AG, Basel.

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

    Science.gov (United States)

    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.

  9. Inflammasome Proteins As Biomarkers of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert W. Keane

    2018-03-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease that affects the brain and spinal cord. The inflammasome is a multiprotein complex that contributes to the innate immune response in animal models of MS as well as in patients with the disease. Important to the care of patients with MS is the need for biomarkers that can predict disease onset, disease exacerbation, as well as response to treatment. In this study, we analyzed serum samples from 32 patients with MS and 120 age-matched controls, and provide receiver operator characteristic (ROC curves with associated confidence intervals following analyses of serum samples from patients with MS, most of which had the relapsing-remitting form of the disease, and from healthy unaffected donors, and determine the sensitivity and specificity of inflammasome proteins as biomarkers of MS. We report that caspase-1 (1.662 ± 0.6024 difference between means, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC (407.5 ± 35.79, and interleukin (IL-18 (78.53 + 17.86 were elevated in the serum of MS patients when compared to controls. Interestingly, the levels of IL-1β (−0.5961 ± 0.265 were lower in the MS cohort. Importantly, the area under the curve (AUC for ASC and caspase-1 were 0.9448 and 0.848, respectively. Taken together, these data suggest that ASC and caspase-1 could be potential candidate biomarkers for MS onset.

  10. Retinal periphlebitis in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Stamenković Miroslav

    2011-01-01

    Full Text Available Background/Aim. Multiple sclerosis (MS is an immunemediated disorder of the central nervous system (CNS, characterized by inflammation, demyelination and axonal loss. Retinal periphlebitis (RP is often present in MS patients with similar evolution and histopathological changes as MS lesions. The aim of this study was to analyze the presence of RP in MS patients during different clinical phases, and its connection with impairment of blood-brain barrier. Methods. The study included 45 patients (26 females and 19 males with MS. Their average age was 33.2 ± 8.1 years. There were 28 patients with relapsing-remitting (RR form, 7 with primary progresive (PP and 10 with secondary progressive (SP form of MS. There were 27 patients in the relapse and 18 patients in the remission phase. The average MS duration was 7.48 ± 1.3 years. Ophthalmological, neurological and MRI examination were performed in all the patients, as well as cerebrospinal fluid sampling. Albumin ratio and IgG index were calculated in all the patients. Results. There were 9 patients with RP, and 36 without it. MS duration was significantly longer in the RP group. RP was much more common in the progressive form and was not present in the remission phase of MS. Albumin ratio values were increased in the group with RP. IgG index and IgG synthesis according to Tourtellotte formula, were statistically higher in the group of patients with RP. The values of visual evoked potentials (VEP's latency were significantly higher in the group of patients with RP. Conclusion. The presence of RP is a reliable indicator of MS activity and might be considered as a parameter for monitoring the disease activity and effects of the treatment.

  11. 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

  12. A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

    KAUST Repository

    Kannan, Venkateshan

    2017-03-29

    Multiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.

  13. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

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    Liu, Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Duan, Yunyun, E-mail: xiaoyun81.love@163.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); He, Yong, E-mail: yong.h.he@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Yu, Chunshui, E-mail: csyuster@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Wang, Jun, E-mail: jun_wang@bnu.edu.cn [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China); Huang, Jing, E-mail: sainthj@126.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Ye, Jing, E-mail: jingye.2007@yahoo.com.cn [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Parizel, Paul M., E-mail: paul.parizel@ua.ac.be [Department of Radiology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, 8 Belgium (Belgium); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shu, Ni, E-mail: nshu55@gmail.com [State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875 (China)

    2012-10-15

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS.

  14. Whole brain white matter changes revealed by multiple diffusion metrics in multiple sclerosis: A TBSS study

    International Nuclear Information System (INIS)

    Liu, Yaou; Duan, Yunyun; He, Yong; Yu, Chunshui; Wang, Jun; Huang, Jing; Ye, Jing; Parizel, Paul M.; Li, Kuncheng; Shu, Ni

    2012-01-01

    Objective: To investigate whole brain white matter changes in multiple sclerosis (MS) by multiple diffusion indices, we examined patients with diffusion tensor imaging and utilized tract-based spatial statistics (TBSS) method to analyze the data. Methods: Forty-one relapsing-remitting multiple sclerosis (RRMS) patients and 41 age- and gender-matched normal controls were included in this study. Diffusion weighted images were acquired by employing a single-shot echo planar imaging sequence on a 1.5 T MR scanner. Voxel-wise analyses of multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were performed with TBSS. Results: The MS patients had significantly decreased FA (9.11%), increased MD (8.26%), AD (3.48%) and RD (13.17%) in their white matter skeletons compared with the controls. Through TBSS analyses, we found abnormal diffusion changes in widespread white matter regions in MS patients. Specifically, decreased FA, increased MD and increased RD were involved in whole-brain white matter, while several regions exhibited increased AD. Furthermore, white matter regions with significant correlations between the diffusion metrics and the clinical variables (the EDSS scores, disease durations and white matter lesion loads) in MS patients were identified. Conclusion: Widespread white matter abnormalities were observed in MS patients revealed by multiple diffusion metrics. The diffusion changes and correlations with clinical variables were mainly attributed to increased RD, implying the predominant role of RD in reflecting the subtle pathological changes in MS

  15. Personality factors in recently diagnosed multiple sclerosis patients: a preliminary investigation with the NEO-FFI scale

    Directory of Open Access Journals (Sweden)

    Aline Braz de Lima

    2015-03-01

    Full Text Available This article describes some prevalent personality dimensions of recently diagnosed multiple sclerosis patients. A sample of 33 female recently diagnosed with relapsing-remitting multiple sclerosis (RRMS was assessed with the NEO-FFI personality scale. Beck depression (BDI and anxiety (BAI scales were also used. No significant levels of anxiety or depression were identified in this group. As for personality factors, conscientiousness was the most common factor found, whereas openness to experience was the least observed. Literature on the relationship between personality and MS is scarce and there are no Brazilian studies on this subject. Some personality traits might complicate or facilitate the experience of living with a chronic, disabling and uncertain neurological condition such as MS.

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

    DEFF Research Database (Denmark)

    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...

  17. Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis.

    Science.gov (United States)

    Ranganathan, Usha; Kaunzner, Ulrike; Foster, Stacyann; Vartanian, Timothy; Perumal, Jai S

    2018-04-01

    Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). Although Immune thrombocytopenia (ITP) has been reported as a secondary autoimmune phenomenon following alemtuzumab infusion, immediate thrombocytopenia during the infusion has not been reported. We report transient, reversible, self-limiting acute-onset thrombocytopenia during the first course with alemtuzumab. In total, 3 of 22 paitents developed mild self-limited bruising associated with a drop in platelet count from their baseline during the intial 5-day course of alemtuzumab. Upon chart review, all 22 patients who received alemtuzumab developed an immediate mostly asymptomatic drop in platelet count which returned to normal within 2 months post-infusion.

  18. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

  19. CSF inflammation and axonal damage are increased and correlate in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Khademi, Mohsen

    2013-01-01

    BACKGROUND: The mechanism underlying disease progression in progressive multiple sclerosis (MS) is uncertain. Pathological studies found widespread inflammation in progressive MS brains correlating with disease progression and axonal damage. OBJECTIVES: To study cerebrospinal fluid (CSF) biomarkers...... and clarify whether inflammation and axonal damage are associated in progressive MS. METHODS: Using enzyme-linked immunosorbent assay (ELISA), we analysed CSF from 40 secondary progressive (SPMS), 21 primary progressive (PPMS), and 36 relapsing-remitting (RRMS) and 20 non-inflammatory neurological disease...... (NIND) patients. Twenty-two of the SPMS patients participated in an MBP8298 peptide clinical trial and had CSF follow-up after one year. RESULTS: Compared to NIND patients, inflammatory biomarkers osteopontin and matrix metalloproteinase-9 (MMP9) were increased in all MS patients while CXCL13...

  20. Visual pathway abnormalities were found in most multiple sclerosis patients despite history of previous optic neuritis

    Directory of Open Access Journals (Sweden)

    Stella Maris Costa Castro

    2013-07-01

    Full Text Available Objective It was to investigate visual field (VF abnormalities in a group of multiple sclerosis (MS patients in the remission phase and the presence of magnetic resonance imaging (MRI lesions in the optic radiations. Methods VF was assessed in 60 participants (age range 20-51 years: 35 relapsing-remitting MS patients [20 optic neuritis (+, 15 optic neuritis (-] and 25 controls. MRI (3-Tesla was obtained in all patients. Results Visual parameters were abnormal in MS patients as compared to controls. The majority of VF defects were diffuse. All patients except one had posterior visual pathways lesions. No significant difference in lesion number, length and distribution was noted between patients with and without history of optic neuritis. One patient presented homonymous hemianopsia. Conclusion Posterior visual pathway abnormalities were found in most MS patients despite history of previous optic neuritis.

  1. Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis

    DEFF Research Database (Denmark)

    Lundell, H; Svolgaard, O; Dogonowski, A-M

    2017-01-01

    OBJECTIVE: To investigate how atrophy is distributed over the cross section of the upper cervical spinal cord and how this relates to functional impairment in multiple sclerosis (MS). METHODS: We analysed the structural brain MRI scans of 54 patients with relapsing-remitting MS (n=22), primary...... progressive MS (n=9), secondary progressive MS (n=23) and 23 age- and sex-matched healthy controls. We measured the cross-sectional area (CSA), left-right width (LRW) and anterior-posterior width (APW) of the spinal cord at the segmental level C2. We tested for a nonparametric linear relationship between...... and specific MSIS subscores. CONCLUSION: In patients with MS, atrophy of the upper cervical cord is most evident in the antero-posterior direction. As APW of the cervical cord can be readily derived from standard structural MRI of the brain, APW constitutes a clinically useful neuroimaging marker of disease...

  2. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    and neurological disability. METHODS: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically......OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...... deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction...

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

    DEFF Research Database (Denmark)

    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...

  4. The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment-sensitive biomarkers

    DEFF Research Database (Denmark)

    Khademi, M.; Bornsen, L.; Rafatnia, F.

    2009-01-01

    BACKGROUND: Natalizumab affects systemic cytokine expressions and clinical course in relapsing-remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP...... showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy. CONCLUSIONS: Natalizumab attenuates pro-inflammatory mediators intrathecally and the reduced pro-inflammatory milieu may allow...... increased production of the anti-inflammatory mediator IL-10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune-modifying treatment which could be used as biomarkers for this therapy Udgivelsesdato...

  5. Spasmodic Dysphonia in Multiple Sclerosis Treatment With Botulin Toxin A: A Pilot Study.

    Science.gov (United States)

    Di Stadio, Arianna; Bernitsas, Evanthia; Restivo, Domenico Antonio; Alfonsi, Enrico; Marchese-Ragona, Rosario

    2018-04-09

    This study aims to evaluate the effect of botulin toxin A in patients with multiple sclerosis (MS) affected by spasmodic dysphonia (SD) and to show the safety and effectiveness of this treatment in long-term observation. This is a pilot study on three relapsing-remitting MS patients with SD and their response to botulin toxin A. None of the patients reported dysphagia or other adverse events. Significant improvement was observed in terms of both voice quality and laryngostroboscopy results. The treatment effect was durable for 6-8 months. Botulin toxin A is a safe treatment that can be successfully used to treat SD in patients with MS. Larger studies are necessary to confirm our results. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  6. MRI outcomes with cladribine tablets for multiple sclerosis in the CLARITY study

    DEFF Research Database (Denmark)

    Comi, Giancarlo; Cook, Stuart D; Giovannoni, Gavin

    2013-01-01

    We herein provide a comprehensive assessment of magnetic resonance imaging (MRI) outcomes from CLARITY, a 96-week, double-blind study demonstrating significant clinical and MRI improvements in patients with relapsing-remitting multiple sclerosis (RRMS) treated with cladribine tablets. Patients...... with RRMS were randomized 1:1:1 to annual short-course therapy with cladribine tablets cumulative dose 3.5 or 5.25 mg/kg or placebo. MRI endpoints included mean number of T1 gadolinium-enhancing (Gd+), active T2 and combined unique (CU) lesions/patient/scan. MRI-measured disease activity was significantly...... reduced in both cladribine tablets groups versus placebo. The proportion of patients with no active lesions at study end was: T1 Gd+ lesions: 86.8 and 91.0 versus 48.3 % (p ...

  7. [Multiple sclerosis. Clinical survey of 50 patients followed at the Ambulatory of Neurology UNIFESP-EPM].

    Science.gov (United States)

    De Oliveira, E M; Annes, M; Oliveira, A S; Gabbai, A A

    1999-03-01

    Multiple sclerosis, seems to be a rare disease however in the population herein studied it is similar to the one described by others, in Brazil and abroad. We studied 50 patients classified according Poser's criteria that were followed at the Department of Neurology UNIFESP-EPM from 1983 to 1995. The clinical findings of these 50 patients were similar to those described in other series. We found a high prevalence among female young patients who presented relapsing-remitting evolution. The most common symptoms were those related to pyramidal and cerebellar dysfunctions. The EDSS score seems to be worse in patients with specific cerebellar and pyramidal signs, higher number of relapses and longer time of disease but it is not related to the number of white matter lesions found at MRI.

  8. Quantitative Magnetic Resonance Imaging of Brainstem Volumes, Plaques, and Surface Area in the Occipital Regions of Patients with Multiple Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Alper, F.; Kantarci, M.; Altunkaynak, E.; Varoglu, A. O.; Karaman, A.; Oral, E.; Okur, A. [Ataturk Univ., Erzurum (Turkey). Depts. of Radiology, Histology, Neurology and Embryology, Psychiatry

    2006-07-15

    Purpose: To determine brainstem volumes, number of plaques, and surface areas in the occipital lobes of patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and to investigate whether there is any correlation between brainstem volume and the number/surface areas of plaque in the occipital lobes. Material and Methods: Magnetic resonance imaging was obtained on 14 relapsing-remitting (RR) and 13 secondary progressive (SP) MS patients and 26 female control subjects. The Cavalieri method was used by modern design stereology to measure brainstem volume. The point-counting grid was used to evaluate sclerotic plaque surface areas in the occipital lobe. The number of plaques in the imaging section was calculated. Results: Brainstem volumes for RR and SP with multiple sclerosis and control subjects were 3647 mm{sup 3} , 3515 mm{sup 3} , and 4517 mm{sup 3} , respectively. Mean number of plaques in the right-left occipital lobe was found to be 2.7-3.4 in RR-MS and 5.2-2.8 in SP-MS. Mean plaque surface area in the right-left occipital lobe was determined to be 58.52-88.24 mm{sup 2} in RR MS and 124.3-64.82 mm{sup 2} in SP MS. Brainstem volumes were significantly reduced in both groups of patients with MS compared to controls ( P <0.01). Conclusion: Magnetic-resonance-estimated volume and surface area values in multiple sclerosis may facilitate our understanding of the clinical situation of patients and provide a simple index for evaluating therapeutic efficiency.

  9. Quantitative Magnetic Resonance Imaging of Brainstem Volumes, Plaques, and Surface Area in the Occipital Regions of Patients with Multiple Sclerosis

    International Nuclear Information System (INIS)

    Alper, F.; Kantarci, M.; Altunkaynak, E.; Varoglu, A. O.; Karaman, A.; Oral, E.; Okur, A.

    2006-01-01

    Purpose: To determine brainstem volumes, number of plaques, and surface areas in the occipital lobes of patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and to investigate whether there is any correlation between brainstem volume and the number/surface areas of plaque in the occipital lobes. Material and Methods: Magnetic resonance imaging was obtained on 14 relapsing-remitting (RR) and 13 secondary progressive (SP) MS patients and 26 female control subjects. The Cavalieri method was used by modern design stereology to measure brainstem volume. The point-counting grid was used to evaluate sclerotic plaque surface areas in the occipital lobe. The number of plaques in the imaging section was calculated. Results: Brainstem volumes for RR and SP with multiple sclerosis and control subjects were 3647 mm 3 , 3515 mm 3 , and 4517 mm 3 , respectively. Mean number of plaques in the right-left occipital lobe was found to be 2.7-3.4 in RR-MS and 5.2-2.8 in SP-MS. Mean plaque surface area in the right-left occipital lobe was determined to be 58.52-88.24 mm 2 in RR MS and 124.3-64.82 mm 2 in SP MS. Brainstem volumes were significantly reduced in both groups of patients with MS compared to controls ( P <0.01). Conclusion: Magnetic-resonance-estimated volume and surface area values in multiple sclerosis may facilitate our understanding of the clinical situation of patients and provide a simple index for evaluating therapeutic efficiency

  10. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis.

    Science.gov (United States)

    Motl, R W; Goldman, M

    2011-02-01

    We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (VO₂(peak) ) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Study 1 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = -0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = -0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = -0.40) had statistically significant associations with VO₂(peak). The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. © 2010 John Wiley & Sons A/S.

  11. Upper limb movement analysis during gait in multiple sclerosis patients.

    Science.gov (United States)

    Elsworth-Edelsten, Charlotte; Bonnefoy-Mazure, Alice; Laidet, Magali; Armand, Stephane; Assal, Frederic; Lalive, Patrice; Allali, Gilles

    2017-08-01

    Gait disorders in multiple sclerosis (MS) are well studied; however, no previous study has described upper limb movements during gait. However, upper limb movements have an important role during locomotion and can be altered in MS patients due to direct MS lesions or mechanisms of compensation. The aim of this study was to describe the arm movements during gait in a population of MS patients with low disability compared with a healthy control group. In this observational study we analyzed the arm movements during gait in 52 outpatients (mean age: 39.7±9.6years, female: 40%) with relapsing-remitting MS with low disability (mean EDSS: 2±1) and 25 healthy age-matched controls using a 3-dimension gait analysis. MS patients walked slower, with increased mean elbow flexion and decreased amplitude of elbow flexion (ROM) compared to the control group, whereas shoulder and hand movements were similar to controls. These differences were not explained by age or disability. Upper limb alterations in movement during gait in MS patients with low disability can be characterized by an increase in mean elbow flexion and a decrease in amplitude (ROM) for elbow flexion/extension. This upper limb movement pattern should be considered as a new component of gait disorders in MS and may reflect subtle motor deficits or the use of compensatory mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. [Information processing speed and influential factors in multiple sclerosis].

    Science.gov (United States)

    Zhang, M L; Xu, E H; Dong, H Q; Zhang, J W

    2016-04-19

    To study the information processing speed and the influential factors in multiple sclerosis (MS) patients. A total of 36 patients with relapsing-remitting MS (RRMS), 21 patients with secondary progressive MS (SPMS), and 50 healthy control subjects from Xuanwu Hospital of Capital Medical University between April 2010 and April 2012 were included into this cross-sectional study.Neuropsychological tests was conducted after the disease had been stable for 8 weeks, including information processing speed, memory, executive functions, language and visual perception.Correlation between information processing speed and depression, fatigue, Expanded Disability Status Scale (EDSS) were studied. (1)MS patient groups demonstrated cognitive deficits compared to healthy controls.The Symbol Digit Modalities Test (SDMT) (control group 57±12; RRMS group 46±17; SPMS group 35±10, Pinformation processing (Pinformation processing speed, verbal memory and executive functioning are seen in MS patients, especially in SPMS subtype, while visual-spatial function is relatively reserved.Age, white matter change scales, EDSS scores, depression are negatively associated with information processing speed.

  13. High-dose contrast-enhanced MRI in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

    1996-05-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

  14. 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.

  15. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julia Krämer

    2015-09-01

    Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  16. Epilepsy in multiple sclerosis: The role of temporal lobe damage.

    Science.gov (United States)

    Calabrese, M; Castellaro, M; Bertoldo, A; De Luca, A; Pizzini, F B; Ricciardi, G K; Pitteri, M; Zimatore, S; Magliozzi, R; Benedetti, M D; Manganotti, P; Montemezzi, S; Reynolds, R; Gajofatto, A; Monaco, S

    2017-03-01

    Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( ptemporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

  17. Psychiatric disorders revealing multiple sclerosis after 20 years of evolvement

    Directory of Open Access Journals (Sweden)

    Aicha Slassi Sennou

    2014-01-01

    Full Text Available Previous research indicates that the onset of psychiatric disorders is sometimes associated with multiple sclerosis (MS evolving several years later. However, information on why this might occur, and on the outcomes of such patients, is still lacking. We aim to discuss these limitations with the current paper. We describe a 51-year-old female who demonstrated severe anxiety disorder and depression years before developing MS neurological symptoms. The patient was treated for these psychiatric disorders over 20 years. In the last 3 years of her treatment, the patient demonstrated a choreic-type of movement disorder in all her limbs. This disorder is consistent with relapsing-remitting MS. Clinical and magnetic resonance imaging (MRI examinations demonstrated aspects of MS, without MS being diagnosed conclusively. The visual evoked potential indicated a diagnosis of conduction abnormalities. The established diagnosis was slow relapsing MS. The patient underwent methylprednisolone bolus (1 g/day. This case-study suggests that health professionals should conduct a full neurological assessment when they find atypical psychiatric symptoms in a patient. This would make sure that patients receive a better standard of care, and thus experience a better quality of life.

  18. High-dose contrast-enhanced MRI in multiple sclerosis

    International Nuclear Information System (INIS)

    Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

    1996-01-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

  19. 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

  20. Rehabilitation and multiple sclerosis

    DEFF Research Database (Denmark)

    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...

  1. 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.

  2. Impact on healthcare resource utilization of multiple sclerosis in Spain.

    Science.gov (United States)

    Sicras-Mainar, Antoni; Ruíz-Beato, Elena; Navarro-Artieda, Ruth; Maurino, Jorge

    2017-12-29

    Multiple sclerosis (MS) is a chronic disease with a high socioeconomic impact. The aim of this study was to assess healthcare resources utilization and costs in a sample of patients with MS. A retrospective, cohort study was conducted using electronic medical records from 19 primary care centres in Asturias and Catalonia, Spain. Adult patients diagnosed with MS were distributed into two groups according to the Expanded Disability Status Scale (EDSS) score: 0-3.5 (no-moderate disability) and 4-9.5 (severe disability). Healthcare (direct cost) and non-healthcare costs (work productivity losses) were analysed. An analysis of covariance (ANCOVA) was used for correction, p < 0.05. A multiple regression model was performed to obtain the variables associated with costs. A total of 222 patients were analyzed; mean (SD) age: 45.5 (12.5) years, 64.4% female, and 62.2% presented a diagnosis of relapsing-remitting MS. Median EDSS score was 2.5, with 68.5% of the patients with no to moderate disability. The mean annual cost per MS patient was €25,103. For no-moderate and severe disability, the ANCOVA-adjusted mean annual cost was €23,157 and €29,242, respectively (p = 0.013). Direct costs and MS disease-modifying therapy accounted for 39.4% and 31.7% of the total costs, respectively. The total costs were associated with number of relapses (β = 0.135, p = 0.001), time since diagnosis (β = 0.281, p = 0.023), and age (β = 0.198, p = 0.037). Multiple sclerosis imposes a substantial economic burden on the Spanish National Health System, patients and society as a whole. Costs significantly correlated with disease progression.

  3. Resting-state connectivity of pre-motor cortex reflects disability in multiple sclerosis.

    Science.gov (United States)

    Dogonowski, A-M; Siebner, H R; Soelberg Sørensen, P; Paulson, O B; Dyrby, T B; Blinkenberg, M; Madsen, K H

    2013-11-01

    To characterize the relationship between motor resting-state connectivity of the dorsal pre-motor cortex (PMd) and clinical disability in patients with multiple sclerosis (MS). A total of 27 patients with relapsing-remitting MS (RR-MS) and 15 patients with secondary progressive MS (SP-MS) underwent functional resting-state magnetic resonance imaging. Clinical disability was assessed using the Expanded Disability Status Scale (EDSS). Independent component analysis was used to characterize motor resting-state connectivity. Multiple regression analysis was performed in SPM8 between the individual expression of motor resting-state connectivity in PMd and EDSS scores including age as covariate. Separate post hoc analyses were performed for patients with RR-MS and SP-MS. The EDSS scores ranged from 0 to 7 with a median score of 4.3. Motor resting-state connectivity of left PMd showed a positive linear relation with clinical disability in patients with MS. This effect was stronger when considering the group of patients with RR-MS alone, whereas patients with SP-MS showed no increase in coupling strength between left PMd and the motor resting-state network with increasing clinical disability. No significant relation between motor resting-state connectivity of the right PMd and clinical disability was detected in MS. The increase in functional coupling between left PMd and the motor resting-state network with increasing clinical disability can be interpreted as adaptive reorganization of the motor system to maintain motor function, which appears to be limited to the relapsing-remitting stage of the disease. © 2013 John Wiley & Sons A/S.

  4. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Directory of Open Access Journals (Sweden)

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  5. Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions.

    Science.gov (United States)

    Gajofatto, A; Turatti, M; Bianchi, M R; Forlivesi, S; Gobbin, F; Azzarà, A; Monaco, S; Benedetti, M D

    2016-03-01

    Benign multiple sclerosis (BMS) definitions rely on physical disability level but do not account sufficiently for cognitive impairment which, however, is not rare. To study the evolution of physical disability and cognitive performance of a group of patients with BMS followed at an University Hospital Multiple Sclerosis Center. A consecutive sample of 24 BMS cases (diagnosis according to 2005 McDonald's criteria, relapsing-remitting course, disease duration ≥ 10 years, and expanded disability status scale [EDSS] score ≤ 2.0) and 13 sex- and age-matched non-BMS patients differing from BMS cases for having EDSS score 2.5-5.5 were included. Main outcome measures were as follows: (i) baseline and 5-year follow-up cognitive impairment defined as failure of at least two tests of the administered neuropsychological battery; (ii) EDSS score worsening defined as confirmed increase ≥ 1 point (or 0.5 point if baseline EDSS score = 5.5). At inclusion, BMS subjects were 41 ± 8 years old and had median EDSS score 1.5 (range 0-2), while non-BMS patients were 46 ± 8 years old and had median EDSS score 3.0 (2.5-5.5). At baseline 16% of patients in both groups were cognitively impaired. After 5 years, EDSS score worsened in 8% of BMS and 46% of non-BMS patients (P = 0.008), while the proportion of cognitively impaired subjects increased to 25% in both groups. Patients with BMS had better physical disability outcome at 5 years compared to non-BMS cases. However, cognitive impairment frequency and decline over time appeared similar. Neuropsychological assessment is essential in patients with BMS given the distinct pathways followed by disease progression in cognitive and physical domains. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Sexual Dysfunction and Incidence of Depression in Multiple Sclerosis Patients

    Science.gov (United States)

    Zavoreo, Iris; Gržinčić, Tihana; Preksavec, Marina; Madžar, Tomislav; Bašić Kes, Vanja

    2016-09-01

    Multiple sclerosis (MS) is one of the most common diseases of the central nervous system and usually occurs at the age when people would be expected to be in the prime of their sexual lives. In everyday practice, sexual dysfunction is underestimated because clinicians mostly concentrate on the classic neurologic deficits and often overlook symptoms that can seriously affect the quality of life. Our study included 98 patients (42 men and 56 women, mean age 35±12 years) with relapse from our MS register, with established diagnosis of relapsing remitting multiple sclerosis according to McDonald criteria. Patients completed the questionnaires (Sexual Satisfaction Scale, SSS and Beck Depression Scale BDS), and underwent neurological assessment (Expanded Disability Status Scale, EDSS). All patients were in the group with EDSS 2 to 4 points (mobile patients). There was no statistically significant difference in BDS and SSS values according to EDSS score. Correlation coefficients were calculated (BDS and SSS) for men (p=0.42) and women (p=0.44), yielding positive correlation. There was no statistically significant difference in BDS and SSS values according to gender, disease duration or immunomodulatory therapy. In our group of patients, despite low EDSS score (fully ambulatory without aid, self sufficient patients) we found positive correlation between sexual dysfunction and depression, showing that even in such patients the quality of life can be decreased. In conclusion, sexual dysfunction and depression are mostly under-recognized by neurologists because they are not part of routine testing; therefore, some additional questionnaires should be used in the evaluation in MS patients, even those with low EDSS score, in order to improve their quality of life.

  7. Brain intra- and extracellular sodium concentration in multiple sclerosis: a 7 T MRI study.

    Science.gov (United States)

    Petracca, Maria; Vancea, Roxana O; Fleysher, Lazar; Jonkman, Laura E; Oesingmann, Niels; Inglese, Matilde

    2016-03-01

    Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. [Multiple sclerosis management system 3D. Moving from documentation towards management of patients].

    Science.gov (United States)

    Schultheiss, T; Kempcke, R; Kratzsch, F; Eulitz, M; Pette, M; Reichmann, H; Ziemssen, T

    2012-04-01

    The increasing therapeutic options for relapsing-remitting multiple sclerosis require a specific treatment and risk management to recognize the individual response as well as potential side effects. To switch from pure MS documentation to MS management by implementing a new multiple sclerosis management and documentation tool may be of importance. This article presents the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and visualization of visit schedules and mandatory examinations via defined study modules by integration of data input from patients, attending physicians and MS nurses. It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information is collected via interactive touch screens. A specific module which is part of MSDS 3D's current version allows the monthly monitoring of patients under treatment with natalizumab. A checklist covering clinical signs of progressive multifocal leukoencephalopathy (PML) and a detailed questionnaire about the handling of natalizumab in practice have additionally been added. The MS patient management system MSDS 3D has successfully been implemented and is currently being evaluated in a multi-centre setting. Advanced assessment of patient data may allow improvements in clinical practice and research work. The addition of a checklist and a questionnaire into the natalizumab module may support the recognition of PML during its early, treatable course.

  9. Intra-individual variability in information processing speed reflects white matter microstructure in multiple sclerosis.

    Science.gov (United States)

    Mazerolle, Erin L; Wojtowicz, Magdalena A; Omisade, Antonina; Fisk, John D

    2013-01-01

    Slowed information processing speed is commonly reported in persons with multiple sclerosis (MS), and is typically investigated using clinical neuropsychological tests, which provide sensitive indices of mean-level information processing speed. However, recent studies have demonstrated that within-person variability or intra-individual variability (IIV) in information processing speed may be a more sensitive indicator of neurologic status than mean-level performance on clinical tests. We evaluated the neural basis of increased IIV in mildly affected relapsing-remitting MS patients by characterizing the relation between IIV (controlling for mean-level performance) and white matter integrity using diffusion tensor imaging (DTI). Twenty women with relapsing-remitting MS and 20 matched control participants completed the Computerized Test of Information Processing (CTIP), from which both mean response time and IIV were calculated. Other clinical measures of information processing speed were also collected. Relations between IIV on the CTIP and DTI metrics of white matter microstructure were evaluated using tract-based spatial statistics. We observed slower and more variable responses on the CTIP in MS patients relative to controls. Significant relations between white matter microstructure and IIV were observed for MS patients. Increased IIV was associated with reduced integrity in more white matter tracts than was slowed information processing speed as measured by either mean CTIP response time or other neuropsychological test scores. Thus, despite the common use of mean-level performance as an index of cognitive dysfunction in MS, IIV may be more sensitive to the overall burden of white matter disease at the microstructural level. Furthermore, our study highlights the potential value of considering within-person fluctuations, in addition to mean-level performance, for uncovering brain-behavior relationships in neurologic disorders with widespread white matter pathology.

  10. Magnetic resonance imaging features of the spinal cord in pediatric multiple sclerosis: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Verhey, Leonard H. [Hospital for Sick Children, Neuroscience and Mental Health, Toronto, ON (Canada); University of Toronto, Institute of Medical Science, Faculty of Medicine, Toronto, ON (Canada); Branson, Helen M.; Shroff, Manohar [Hospital for Sick Children, Department of Diagnostic Imaging (Neuroradiology), Toronto, ON (Canada); University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Makhija, Monica [Hospital for Sick Children, Neuroscience and Mental Health, Toronto, ON (Canada); Banwell, Brenda [Hospital for Sick Children, Neuroscience and Mental Health, Toronto, ON (Canada); University of Toronto, Institute of Medical Science, Faculty of Medicine, Toronto, ON (Canada); University of Toronto, Department of Pediatrics (Neurology), Toronto, ON (Canada)

    2010-12-15

    Spinal cord lesions in adults with multiple sclerosis (MS) are thought to contribute to disability. The magnetic resonance imaging (MRI) appearance and clinical correlates of spinal cord lesions in children with MS have not been reported. T1-weighted pre- and post-gadolinium and T2-weighted TSE/FSE spine MR images of 36 children (age, 14.3 {+-} 3.3) with relapsing-remitting MS (annualized relapse rate, 0.7; disease duration, 7.5 {+-} 3.3 years) were analyzed for total lesion count, lesion location and length, intramedullary extent, and gadolinium enhancement. Clinical, demographic, laboratory, and MRI data were correlated. Lesions preferentially involved the cervical region, were predominantly focal, and involved only a portion of the transverse cord diameter. However, ten of 36 patients demonstrated longitudinally extensive lesions. Children with the highest clinical relapse rate also tended to have more spinal cord lesions and were more likely to accrue new lesions on serial spinal scans. These preliminary data suggest that MS lesions of the spinal cord in children are radiographically similar to that of adult-onset MS - supporting a common biology of pediatric- and adult-onset disease. However, children with relapsing-remitting MS can also develop longitudinally extensive lesions, suggesting that such lesions may be less specific for diseases such as neuromyelitis optica in pediatric patients. All patients recovered well from spinal cord attacks, and the presence of spinal cord lesions in the first few years of disease did not correlate with physical disability. Measures of spinal cord atrophy and longer periods of observation are required to determine the impact of spinal cord involvement in pediatric-onset MS. (orig.)

  11. Magnetic resonance imaging features of the spinal cord in pediatric multiple sclerosis: a preliminary study

    International Nuclear Information System (INIS)

    Verhey, Leonard H.; Branson, Helen M.; Shroff, Manohar; Makhija, Monica; Banwell, Brenda

    2010-01-01

    Spinal cord lesions in adults with multiple sclerosis (MS) are thought to contribute to disability. The magnetic resonance imaging (MRI) appearance and clinical correlates of spinal cord lesions in children with MS have not been reported. T1-weighted pre- and post-gadolinium and T2-weighted TSE/FSE spine MR images of 36 children (age, 14.3 ± 3.3) with relapsing-remitting MS (annualized relapse rate, 0.7; disease duration, 7.5 ± 3.3 years) were analyzed for total lesion count, lesion location and length, intramedullary extent, and gadolinium enhancement. Clinical, demographic, laboratory, and MRI data were correlated. Lesions preferentially involved the cervical region, were predominantly focal, and involved only a portion of the transverse cord diameter. However, ten of 36 patients demonstrated longitudinally extensive lesions. Children with the highest clinical relapse rate also tended to have more spinal cord lesions and were more likely to accrue new lesions on serial spinal scans. These preliminary data suggest that MS lesions of the spinal cord in children are radiographically similar to that of adult-onset MS - supporting a common biology of pediatric- and adult-onset disease. However, children with relapsing-remitting MS can also develop longitudinally extensive lesions, suggesting that such lesions may be less specific for diseases such as neuromyelitis optica in pediatric patients. All patients recovered well from spinal cord attacks, and the presence of spinal cord lesions in the first few years of disease did not correlate with physical disability. Measures of spinal cord atrophy and longer periods of observation are required to determine the impact of spinal cord involvement in pediatric-onset MS. (orig.)

  12. Longitudinal follow-up with MR imaging and Gd-DTPA to assess the evolution of multiple sclerosis

    International Nuclear Information System (INIS)

    Berry, I.; Manelfe, C.; Bensemhoun, C.; Mekies, C.; Clanet, M.

    1990-01-01

    This paper assesses whether the changes seen on longitudinal follow-up with Gd-DTPA-enhanced MR imaging can help in evaluating the prognosis of multiple sclerosis (MS). Thirty patients with definite MS (relapsing-remitting in 22, progressive-chronic in eight) underwent 54 MR studies performed during disease evolution (21 relapses prior to steroid treatment, eight chronic progressions) and stability (n = 25). Another group of seven patients underwent repetitive MR imaging every 3 months (eight to 10 controls) and also during relapses. MR imaging was performed at 0.5 T with T1- and T2-weighted sequences; Gd-DTPA was injected intravenously (0.1 mmol/kg)

  13. Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

    Science.gov (United States)

    Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

    2017-04-01

    Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

  14. Lack of CD4+ T cell percent decrease in alemtuzumab-treated multiple sclerosis patients with persistent relapses.

    Science.gov (United States)

    Rolla, Simona; De Mercanti, Stefania Federica; Bardina, Valentina; Horakova, Dana; Habek, Mario; Adamec, Ivan; Cocco, Eleonora; Annovazzi, Pietro; Vladic, Anton; Novelli, Francesco; Durelli, Luca; Clerico, Marinella

    2017-12-15

    Alemtuzumab, a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), induces lymphopenia especially of CD4+ T cells. Here, we report the atypical CD4+ T population behaviour of two patients with persistent disease activity despite repeated alemtuzumab treatments. Whereas lymphocytes count decreased and fluctuated accordingly to alemtuzumab administration, their CD4+ cell percentage was not or just mildly affected and was slightly below the lowest normal limit already before alemtuzumab. These cases anticipate further studies aimed to investigate whether the evaluation of the CD4+ cell percentage could represent a helpful tool to address the individual clinical response to alemtuzumab. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. The nature of verbal memory impairment in multiple sclerosis: a list-learning and meta-analytic study.

    Science.gov (United States)

    Lafosse, Jose M; Mitchell, Sandra M; Corboy, John R; Filley, Christopher M

    2013-10-01

    The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing.

  16. 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 ...

  17. [Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

    Science.gov (United States)

    Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

    To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. Urea cycle disorder misdiagnosed as multiple sclerosis: a case report and review of the literature.

    Science.gov (United States)

    Algahtani, Hussein; Alameer, Seham; Marzouk, Yousef; Shirah, Bader

    2018-04-01

    Urea cycle disorders are a group of inborn errors of metabolism caused by dysfunction of any of the six enzymes or two transport proteins involved in urea biosynthesis. In this paper, we report a patient who presented with neurological dysfunction and coma in the immediate postpartum period. She was misdiagnosed for many years as a case of multiple sclerosis. The importance of reporting this case is to illustrate that the wrong diagnosis of patients as being affected with multiple sclerosis for many years due to magnetic resonance imaging abnormalities rather than the classic relapsing-remitting nature of the disease may lead to catastrophic consequences. The patient was treated with intravenous steroids several times, which is contraindicated in patients with urea cycle disorders as it may precipitate acute hyperammonemic attacks. In addition, the management of urea cycle disorder could have started earlier and avoided multiple admissions to the intensive care unit. We believe that the presence of symmetric hyperintense insular cortical changes are seen in multiple hyperammonemic processes, and in the context of the clinical presentation and high ammonia levels can be suggestive of a urea cycle disorder. For any patient presenting with atypical clinical features, images should be reviewed and discussed in detail with an experienced neuroradiologist. In addition, the ammonia levels should be checked if a urea cycle disorder is suspected.

  4. Acute Responses of a Physical Training Session with a Nintendo Wii on Hemodynamic Variables of an Individual with Multiple Sclerosis.

    Science.gov (United States)

    Monteiro Junior, Renato Sobral; Dantas, Aretha; de Souza, Cíntia Pereira; da Silva, Elirez Bezerra

    2012-12-01

    Multiple sclerosis is a neurological illness that decreases motor functions. This disease can cause weakness of cardiorespiratory muscles and impaired functional capacity and quality of life. Therefore it requires preventive treatments. This study investigated the acute responses of a virtual physical training session with the Nintendo(®) (Kyoto, Japan) Wii™ on hemodynamic variables of an individual with multiple sclerosis (relapsing-remitting). A 34-year-old man with multiple sclerosis with previous experience in aerobic, strength, and functional training (2 years) was tested. His Expanded Disability Status Scale was 2.5. We compared the heart rate, blood pressure, and double product obtained at rest and during (heart rate) and after the Nintendo Wii games "Boxing" and "Sword Play." In rest, the variables were measured in the supine position. Our results showed positive hemodynamic alterations after execution of both games. The peak of heart rate was 121 beats per minute (65% of maximal heart rate) and 104 beats per minute (56% of maximal heart rate) for "Boxing" and "Sword Play," respectively. The training session with "Boxing" was able to stimulate the heart rate to achieve the recommended values for the maintenance of physical fitness in accordance with the American College of Sports Medicine guidelines. We conclude that an exercise training program with the Nintendo Wii may improve physical fitness in people with multiple sclerosis. Moreover, these activities could improve affective status and perhaps maintain the individual engaged at treatment program.

  5. 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

  6. 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...

  7. 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...

  8. 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.

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

    Science.gov (United States)

    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.

  10. Finger and foot tapping as alternative outcomes of upper and lower extremity function in multiple sclerosis.

    Science.gov (United States)

    Tanigawa, Makoto; Stein, Jason; Park, John; Kosa, Peter; Cortese, Irene; Bielekova, Bibiana

    2017-01-01

    While magnetic resonance imaging contrast-enhancing lesions represent an excellent screening tool for disease-modifying treatments in relapsing-remitting multiple sclerosis (RRMS), this biomarker is insensitive for testing therapies against compartmentalized inflammation in progressive multiple sclerosis (MS). Therefore, alternative sensitive outcomes are needed. Using machine learning, clinician-acquired disability scales can be combined with timed measures of neurological functions such as walking speed (e.g. 25-foot walk; 25FW) or fine finger movements (e.g. 9-hole peg test; 9HPT) into sensitive composite clinical scales, such as the recently developed combinatorial, weight-adjusted disability scale (CombiWISE). Ideally, these complementary simplified measurements of certain neurological functions could be performed regularly at patients' homes using smartphones. We asked whether tests amenable to adaptation to smartphone technology, such as finger and foot tapping have comparable sensitivity and specificity to current non-clinician-acquired disability measures. We observed that finger and foot tapping can differentiate RRMS and progressive MS in a cross-sectional study and can also measure yearly and two-year disease progression in the latter, with better power (based on z-scores) in comparison to currently utilized 9HPT and 25FW. Replacing the 9HPT and 25FW with simplified tests broadly adaptable to smartphone technology may enhance the power of composite scales for progressive MS.

  11. New insights into the burden and costs of multiple sclerosis in Europe.

    Science.gov (United States)

    Kobelt, Gisela; Thompson, Alan; Berg, Jenny; Gannedahl, Mia; Eriksson, Jennifer

    2017-07-01

    The current focus in multiple sclerosis (MS) is on early diagnosis and drug intervention, with a view to modifying disease progression. Consequently, healthcare costs have shifted from inpatient care and rehabilitation to outpatient care. This European burden of illness study provides data that can be combined with other evidence to assess whether management approaches provide value to society. A cross-sectional study was conducted in 16 countries. Patients reported on their disease, health-related quality of life (HRQoL) and resource consumption. Descriptive analyses were performed by disease severity. Costs are reported from a societal perspective in 2015€ PPP (adjusted for purchasing power parity). The 16,808 participants had a mean age of 51.5 years, and 52% had relapsing-remitting multiple sclerosis (RRMS). Work capacity declined from 82% to 8%, and utility declined from normal population values to less than zero with advancing disease. Mean costs were 22,800€ PPP in mild, 37,100€ PPP in moderate and 57,500€ PPP in severe disease; healthcare accounted for 68%, 47% and 26%, respectively. Fatigue and cognitive difficulties were reported by 95% and 71% of participants, respectively; both had a significant independent effect on utility. Costs and utility were highly correlated with disease severity, but resource consumption was heavily influenced by healthcare systems organisation and availability of services.

  12. Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis.

    Science.gov (United States)

    Lundell, H; Svolgaard, O; Dogonowski, A-M; Romme Christensen, J; Selleberg, F; Soelberg Sørensen, P; Blinkenberg, M; Siebner, H R; Garde, E

    2017-10-01

    To investigate how atrophy is distributed over the cross section of the upper cervical spinal cord and how this relates to functional impairment in multiple sclerosis (MS). We analysed the structural brain MRI scans of 54 patients with relapsing-remitting MS (n=22), primary progressive MS (n=9), secondary progressive MS (n=23) and 23 age- and sex-matched healthy controls. We measured the cross-sectional area (CSA), left-right width (LRW) and anterior-posterior width (APW) of the spinal cord at the segmental level C2. We tested for a nonparametric linear relationship between these atrophy measures and clinical impairments as reflected by the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impairment Scale (MSIS). In patients with MS, CSA and APW but not LRW were reduced compared to healthy controls (P<.02) and showed significant correlations with EDSS, MSIS and specific MSIS subscores. In patients with MS, atrophy of the upper cervical cord is most evident in the antero-posterior direction. As APW of the cervical cord can be readily derived from standard structural MRI of the brain, APW constitutes a clinically useful neuroimaging marker of disease-related neurodegeneration in MS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

    Directory of Open Access Journals (Sweden)

    Sahar Vesal

    2016-01-01

    Full Text Available Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS disease duration on personality type A and B in relation to individuals' behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18 based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years, 38% (5-10 years, 20% (10-20 years, and 12% (more than 20 years. Significant relationship was observed between disease duration and tendency to type A (higher stress. This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B.

  14. Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka

    Directory of Open Access Journals (Sweden)

    S. M. K. Gamage

    2018-01-01

    Full Text Available Multiple sclerosis (MS is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP results, oligoclonal bands (OCB, and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

  15. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.; Button, Tom; Tuohy, Orla C.; Jones, Joanne L.; May, Karen; Somerfield, Jennifer; Green, Alison J E; Giovannoni, Gavin; Compston, Alastair D.; Fahey, Michael T.; Coles, Alasdair J.

    2011-01-01

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  16. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  17. SIMULTANEOUS DISC HERNIATION IN PATIENTS WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Kalina V. Drenska

    2013-04-01

    Full Text Available Background: Multiple sclerosis (MS is a chronic autoimmune, inflammatory demyelinating disease of the central nervous system. Commonly, MS patients present with accompanying degenerative vertebral disc diseases. Simultaneous disc herniations situated in the cervical or lumbosacral spine can mimic the clinical symptoms of MS and worsen patients’ quality of life.Objective: to investigate the incidence rate and clinical impact of accompanying disc herniations in patients with MS.Material and methods: Our study covered 330 patients (220 females and 110 males, mean age 40.5±12.4 years with clinically definite MS, according to McDonald’s criteria. Comprehensive neurological examinations, EDSS (Expanded Disability Status Scale assessments, and MRI neuroimaging were carried out. Statistical data processing was performed by using the method of variation analysis.Results: Relapsing-remitting MS (RRMS was diagnosed in 280 patients while 50 patients presented with secondary progressive MS (SPMS. Disc herniation was found in 64 (19.4% of our patients. Cervical disc pathology was detected in 38 patients (11.5% of the cases and lumbosacral - in 26 (7.9% of the cases. EDSS scores ranged from 2.5 to 5.5. EDSS evaluation showed statistically significantly worse scores in MS patients with disc herniation comorbidity (p<0, 05.Conclusion: Our own data confirm the assumption that MS patients often present with accompanying degenerative disc pathology. We suggest that comorbidity of disc herniation and MS exert an additional unfavorable effect on patient’s disability and individual quality of life.

  18. Primary progressive multiple sclerosis diagnostic criteria: a reappraisal.

    Science.gov (United States)

    Montalban, X; Sastre-Garriga, J; Filippi, M; Khaleeli, Z; Téllez, N; Vellinga, M M; Tur, C; Brochet, B; Barkhof, F; Rovaris, M; Miller, D H; Polman, C H; Rovira, A; Thompson, A J

    2009-12-01

    The diagnostic criteria used in primary progressive (PP) and relapsing-remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years - PPMS-1): C1: Barkhof-Tintoré (as in 2005 McDonald's criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald's criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald's criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria.

  19. Relapses in Multiple Sclerosis: Definition, Pathophysiology, Features, Imitators, and Treatment

    Directory of Open Access Journals (Sweden)

    Serhan Sevim

    2016-09-01

    Full Text Available Relapse in multiple sclerosis (MS is defined as a neurologic deficit associated with an acute inflammatory demyelinating event that lasts at least 24 hours in the absence of fever and infection. Myelinoclasis and axonal transection occur in relapses. Diagnosis, prognosis, treatment, and many other features of the disease are directly related to the relapses. MS starts as the relapsing-remitting (RRMS form in 85% of patients. A large number of relapses in the first years, polysymptomatic relapses, and pyramidal system, brain stem, and spinal cord involvement are signs of a poor outcome. The average frequency of relapses is approximately one per year during the first years of RRMS. The frequency of relapses increases during systemic infections, psychological stress, and in the postpartum first 3 months. Seventy-five percent of relapses are monosymptomatic. Pseudo-relapses and paroxysmal symptoms are distinguished from relapses by their sudden onset, sudden termination, and shorter duration. Contrast enhancement is valuable in imaging, but undetectable in most relapses. The regression in the first few weeks of relapses is explained by reduction of the edema, and by remyelination in the following months. Relapses and their features are also among the main determinants of treatment. High-dose methylprednisolone and early treatment with adrenocorticotropic hormone reduce post-relapse disability and shorten the duration of relapses. Plasmapheresis is a good option for patients who do not respond to steroid treatment. Identification of relapses by patients and physicians, distinguishing them from imitators, proper evaluation, treatment when necessary, and monitoring the results are of great importance for patients with MS. The educational levels of patients and physicians regarding these parameters should be increased. Well-designed studies that evaluate the long-term effect of relapse treatment on disability are needed.

  20. Altered serotonin transporter availability in patients with multiple sclerosis

    International Nuclear Information System (INIS)

    Hesse, Swen; Sabri, Osama; Moeller, Franziska; Thomae, Eva; Then Bergh, Florian; Petroff, David; Lobsien, Donald; Luthardt, Julia; Becker, Georg-Alexander; Patt, Marianne; Seese, Anita; Meyer, Philipp M.; Regenthal, Ralf

    2014-01-01

    Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET. Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [ 11 C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Wuerzburger Erschoepfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability. Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p = 0.05). Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS. (orig.)

  1. Neuroinflammatory component of gray matter pathology in multiple sclerosis.

    Science.gov (United States)

    Herranz, Elena; Giannì, Costanza; Louapre, Céline; Treaba, Constantina A; Govindarajan, Sindhuja T; Ouellette, Russell; Loggia, Marco L; Sloane, Jacob A; Madigan, Nancy; Izquierdo-Garcia, David; Ward, Noreen; Mangeat, Gabriel; Granberg, Tobias; Klawiter, Eric C; Catana, Ciprian; Hooker, Jacob M; Taylor, Norman; Ionete, Carolina; Kinkel, Revere P; Mainero, Caterina

    2016-11-01

    In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with 11 C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent 11 C-PBR28 MR-PET. MS subjects underwent 7T T2*-weighted imaging for cortical lesion segmentation, and neurological and cognitive evaluation. 11 C-PBR28 binding was measured using normalized 60- to 90-minute standardized uptake values and volume of distribution ratios. Relative to controls, MS subjects exhibited abnormally high 11 C-PBR28 binding across the brain, the greatest increases being in cortex and cortical lesions, thalamus, hippocampus, and NAWM. MS WM lesions showed relatively modest TSPO increases. With the exception of cortical lesions, where TSPO expression was similar, 11 C-PBR28 uptake across the brain was greater in SPMS than in RRMS. In MS, increased 11 C-PBR28 binding in cortex, deep GM, and NAWM correlated with neurological disability and impaired cognitive performance; cortical thinning correlated with increased thalamic TSPO levels. In MS, neuroinflammation is present in the cortex, cortical lesions, deep GM, and NAWM, is closely linked to poor clinical outcome, and is at least partly linked to neurodegeneration. Distinct inflammatory-mediated factors may underlie accumulation of cortical and WM lesions. Quantification of TSPO levels in MS could prove to be a sensitive tool for evaluating in vivo the inflammatory component of GM pathology, particularly in cortical lesions. Ann Neurol 2016;80:776-790. © 2016 American Neurological Association.

  2. Clinical experiences with cannabinoids in spasticity management in multiple sclerosis.

    Science.gov (United States)

    Lorente Fernández, L; Monte Boquet, E; Pérez-Miralles, F; Gil Gómez, I; Escutia Roig, M; Boscá Blasco, I; Poveda Andrés, J L; Casanova-Estruch, B

    2014-06-01

    Spasticity is a common symptom among patients with multiple sclerosis (MS). This study aims to assess the effectiveness and safety of the combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in clinical practice for the treatment of spasticity in MS. Retrospective observational study with patients treated with inhaled THC/CBD between April 2008 and March 2012. Descriptive patient and treatment variables were collected. Therapeutic response was evaluated based on the doctor's analysis and overall impression. Of the 56 patients who started treatment with THC/CBD, 6 were excluded because of missing data. We evaluated 50 patients (42% male) with a median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%). Treatment was discontinued in 16 patients because of ineffectiveness (7 patients), withdrawal (4), and adverse effects (5). The median exposure time in patients whose treatment was discontinued was 30 days vs 174 days in those whose treatment continued at the end of the study. THC/CBD was effective in 80% of patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1), nausea (1), and paranoid ideation (1). THC/CBD appears to be a good alternative to standard treatment as it improves refractory spasticity in MS and has an acceptable toxicity profile. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  3. Longitudinal relationships among posturography and gait measures in multiple sclerosis.

    Science.gov (United States)

    Fritz, Nora E; Newsome, Scott D; Eloyan, Ani; Marasigan, Rhul Evans R; Calabresi, Peter A; Zackowski, Kathleen M

    2015-05-19

    Gait and balance dysfunction frequently occurs early in the multiple sclerosis (MS) disease course. Hence, we sought to determine the longitudinal relationships among quantitative measures of gait and balance in individuals with MS. Fifty-seven ambulatory individuals with MS (28 relapsing-remitting, 29 progressive) were evaluated using posturography, quantitative sensorimotor and gait measures, and overall MS disability with the Expanded Disability Status Scale at each session. Our cohort's age was 45.8 ± 10.4 years (mean ± SD), follow-up time 32.8 ± 15.4 months, median Expanded Disability Status Scale score 3.5, and 56% were women. Poorer performance on balance measures was related to slower walking velocity. Two posturography measures, the anterior-posterior sway and sway during static eyes open, feet apart conditions, were significant contributors to walk velocity over time (approximate R(2) = 0.95), such that poorer performance on the posturography measures was related to slower walking velocity. Similarly, the anterior-posterior sway and sway during static eyes closed, feet together conditions were also significant contributors to the Timed 25-Foot Walk performance over time (approximate R(2) = 0.83). This longitudinal cohort study establishes a strong relationship between clinical gait measures and posturography. The data show that increases in static posturography and reductions in dynamic posturography are associated with a decline in walk velocity and Timed 25-Foot Walk performance over time. Furthermore, longitudinal balance measures predict future walking performance. Quantitative walking and balance measures are important additions to clinical testing to explore longitudinal change and understand fall risk in this progressive disease population. © 2015 American Academy of Neurology.

  4. Stress Urinary Incontinence in Women With Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Caroline Massot

    2016-09-01

    Full Text Available Purpose To report the prevalence and risk factors of stress urinary incontinence (SUI and the prevalence of intrinsic sphincter deficiency in women with multiple sclerosis (MS. Methods We conducted a retrospective study. Female patients with MS, followed for lower urinary tract symptoms (LUTS during a 15-year period were included. Demographic data, MS history, expanded disability status scale (EDSS score at the urodynamic visit, obstetrical past, birth weight, LUTS, and urodynamic findings were collected. SUI was defined as incontinence during cough, or any effort. A maximum urethral closure pressure less than 30 cm H2O defined intrinsic sphincter deficiency. Results We included 363 women with a mean age of 46.7±10.8 years and a mean disease duration of 12.9±8.7 years. The incidence of relapsing remitting MS, a secondary progressive form, and a primary progressive form was 60.6%, 32.8%, and 6.6%, respectively. The prevalence of SUI was 31.4%. The prevalence of intrinsic sphincter deficiency was 1.4% and 0.8% of these patients had a SUI (P=0.300. In a multivariate analysis, women with a SUI had significantly higher birth weight (P=0.030, a pelvic organ prolapse (P=0.021, urgent urinary incontinence (P=0.006, a lower EDSS score (P=0.019, and a weaker containing effort (P<0.001. Conclusions The prevalence of SUI in women with MS was 31.4%. This symptom could affect the quality of life of women with MS.

  5. Diffusion Weighted Imaging in Acute Attacks of Multiple Sclerosis

    International Nuclear Information System (INIS)

    Davoudi, Yasmin; Foroughipour, Mohsen; Torabi, Reza; Layegh, Parvaneh; Matin, Nassim; Shoeibi, Ali

    2016-01-01

    Multiple sclerosis (MS) is one of the most common autoimmune disorders of the central nervous system. In spite of various imaging modalities, the definitive diagnosis of MS remains challenging. This study was designed to evaluate the usefulness of diffusion weighted imaging (DWI) in the diagnosis of acute MS attack and to compare its results with contrast enhanced MRI (CE-MRI). In this cross sectional study, seventy patients with definite diagnosis of relapsing-remitting MS were included. CE-MRI using 0.1 mmol/kg gadolinium as well as DWI sequences were performed for all patients. The percentage of patients with positive DWI was compared with the results of CE-MRI and the consistency between the two imaging modalities was evaluated. Moreover, the relationship between the time of onset of patient’s symptoms and test results for both methods were investigated. CE-MRI yielded positive results for 61 (87%) patients and DWI yielded positive for 53 (76%) patients. In fifty patients (71.42%), both tests were positive and in six cases (8.57%), both were negative. The test results of three patients turned out to be positive in DWI, while they tested negative in CE-MRI. There was no significant relationship between the results of CE-MRI as well as DWI and the time of imaging from the onset of symptoms. These data indicate that while CE-MRI will depict more positive results, there are cases in which DWI will show a positive result while CE-MRI is negative. We suggest that the combination of these two imaging modalities might yield more positive results in diagnosing acute MS attack giving rise to a more accurate diagnosis

  6. Altered serotonin transporter availability in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Hesse, Swen; Sabri, Osama [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Integrated Research and Treatment Center (IFB) Adiposity Diseases, University of Leipzig, Leipzig (Germany); Moeller, Franziska; Thomae, Eva; Then Bergh, Florian [University of Leipzig, Department of Neurology, Leipzig (Germany); Petroff, David [University of Leipzig, Coordinating Centre for Clinical Studies, Leipzig (Germany); Lobsien, Donald [University of Leipzig, Department of Neuroradiology, Leipzig (Germany); Luthardt, Julia; Becker, Georg-Alexander; Patt, Marianne; Seese, Anita; Meyer, Philipp M. [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Regenthal, Ralf [University of Leipzig, Clinical Pharmacology, Rudolf-Boehm-Institute of Pharmacology and Toxicology, Leipzig (Germany)

    2014-05-15

    Modulation of the immune system by the CNS may involve serotonergic regulation via the brain serotonin transporters (SERT). This regulation may be disturbed in patients with CNS disorders including multiple sclerosis (MS). Central serotonergic mechanisms have not been investigated in MS by in vivo imaging. The objective of the study was to assess the availability of SERT in antidepressant-naive patients with MS by means of PET. Included in this study were 23 patients with MS and 22 matched healthy volunteers who were investigated with PET and the SERT-selective marker [{sup 11}C]DASB, and distribution volume ratios were determined. Clinical assessment of the patients included the expanded disability status scale, the MS fatigue scale Wuerzburger Erschoepfungsinventar bei MS (WEIMuS) and the Beck Depression Inventory (BDI). The PET data were analysed with both volume-of-interest and voxel-based analyses to determine regional SERT availability. Patients had lower SERT availability in the cingulate cortex, the thalamus and the insula, and increased availability in the orbitofrontal cortex. Patients with relapsing/remitting MS tended to have lower SERT in the hippocampus, whereas patients with primary progressive disease showed increased SERT availability in prefrontal regions. There was a positive correlation between SERT availability in the insula and both depression and fatigue scores (r = 0.56 vs. BDI, p = 0.02; r = 0.49 vs. WEIMuS, p = 0.05). Serotonergic neurotransmission in MS patients is altered in limbic and paralimbic regions as well as in the frontal cortex that this appears to contribute to psychiatric symptoms of MS. (orig.)

  7. Chaos theory for clinical manifestations in multiple sclerosis.

    Science.gov (United States)

    Akaishi, Tetsuya; Takahashi, Toshiyuki; Nakashima, Ichiro

    2018-06-01

    Multiple sclerosis (MS) is a demyelinating disease which characteristically shows repeated relapses and remissions irregularly in the central nervous system. At present, the pathological mechanism of MS is unknown and we do not have any theories or mathematical models to explain its disseminated patterns in time and space. In this paper, we present a new theoretical model from a viewpoint of complex system with chaos model to reproduce and explain the non-linear clinical and pathological manifestations in MS. First, we adopted a discrete logistic equation with non-linear dynamics to prepare a scalar quantity for the strength of pathogenic factor at a specific location of the central nervous system at a specific time to reflect the negative feedback in immunity. Then, we set distinct minimum thresholds in the above-mentioned scalar quantity for demyelination possibly causing clinical relapses and for cerebral atrophy. With this simple model, we could theoretically reproduce all the subtypes of relapsing-remitting MS, primary progressive MS, and secondary progressive MS. With the sensitivity to initial conditions and sensitivity to minute change in parameters of the chaos theory, we could also reproduce the spatial dissemination. Such chaotic behavior could be reproduced with other similar upward-convex functions with appropriate set of initial conditions and parameters. In conclusion, by applying chaos theory to the three-dimensional scalar field of the central nervous system, we can reproduce the non-linear outcome of the clinical course and explain the unsolved disseminations in time and space of the MS patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Interferon Treatment of Multiple Sclerosis

    OpenAIRE

    Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

    2012-01-01

    Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

  9. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  11. Gender as a prognostic factor and its impact on the incidence of multiple sclerosis in Lorraine, France.

    Science.gov (United States)

    Debouverie, M

    2009-11-15

    We sought to identify (a) the change of incidence rates among gender from 1990 to 2002 from the LORSEP (Lorraine Multiple Sclerosis) population-based cohort, and (b) the role of gender as a predictive demographic factor of disability during the initial course of the disease among multiple sclerosis (MS) patients. The incidence rates of multiple sclerosis (MS) in Lorraine, France, have significantly increased in women, but not in men, from 1990 to 2002 but this increase in incidence of MS was not related to a better ascertainment of patients with mild disability. A total of 2871 MS patients were analyzed. For relapsing-remitting (RR) patients, a multivariate analysis showed that a shorter time to the assignment of an EDSS score of 3 and 4 was associated with the late onset MS, incomplete recovery from the first relapse and a high number of relapses during the first 5 years after the MS onset. Median times were not influenced by gender or by time between the first two relapses. The data were very different for the time between the assignment of scores of 4 and 6, since the median times were not influenced by any of the predicting variables.

  12. 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.

  13. Assessment of cognition using the Rao's Brief Repeatable Battery of Neuropsychological Tests on a group of Brazilian patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Joseph Bruno Bidin Brooks

    2011-12-01

    Full Text Available To assess the cognition of patients with multiple sclerosis (MS using the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB-N. METHOD: BRB-N was translated and adapted for control subjects. Subsequently, it was applied to a group of patients with relapsing-remitting (RR MS. RESULTS: The assessment on the healthy controls (n=47 showed that the correlation between tests on the same cognitive domain was high and that there was a five-factor solution that explained 90% of the total variance. Except for the Word List Generation subset of tests, the performance of patients with RRMS (n=39 was worse than that of the healthy controls. CONCLUSION: BRB-N is a relatively simple method to assess cognition of patients with MS in the daily clinic. It does not take long to apply and does not require special skills or equipment.

  14. Association of Expanded Disability Status Scale and Cytokines after Intervention with Co-supplemented Hemp Seed, Evening Primrose Oils and Hot-natured Diet in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Behzad Baradaran

    2013-02-01

    Full Text Available Introduction: Multiple sclerosis (MS is an inflammatory demyelinating disease of the central nervous system (CNS. Because of limited efficacy and adverse side effects, identifying novel therapeutic and protective agents is important. The aim of this study is to examine the correlations between expanded disability status scale (EDSS and cytokines after intervention with co-supplemented hemp seed and evening primrose oils and hot-natured diet in patients with relapsing-remitting multiple sclerosis (RRMS. Methods: We studied a group of 23 patients with clinically definite RRMS, with EDSS<6 who received co-supplemented hemp seed and evening primrose oils with advising hot-natured diet. Clinically EDSS and immunological factors (plasma cytokines of IL-4, IFN-γ and IL-17 were assessed at baseline and after 6 months. Results: Mean follow-up was 180±2.9 days (N=23, 7 Male and 16 Females aged 25.0±7.5 years with disease duration 6.26±3.9 years. After 6 months, significant improvements in extended disability status score were found in the patients in agreement with decrease cytokines of IFN-γ and IL-17 and increase cytokines of IL-4. Clinical and immunological parameters showed improvement in the patients after the intervention. Conclusion: Our study shows that co-supplemented hemp seed and evening primrose oils with hot-natured diet can have beneficial effects in improving clinical symptoms in relapsing remitting MS patients and significant correlation was found between EDSS and immunological findings.

  15. Cognitive performance of neuromyelitis optica patients: comparison with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Sandra Vanotti

    2013-06-01

    Full Text Available The aim of the present research was to investigate cognitive pattern of patients with neuromyelitis optica (NMO and to compare it with multiple sclerosis (MS patients' performance. Methods: Fourteen NMO, 14 relapsing remitting multiple sclerosis (RRMS, and 14 healthy control patients participated in the investigation. Neuropsychological functions were evaluated with the Brief Repeatable Neuropsychological Battery for MS; Symbol Digit Modalities Test; Digit Span; and Semantic Fluency. Results: Fifty-seven percent of NMO patients and 42.85% of the MS ones had abnormal performance in at least two cognitive tests. The NMO Group showed abnormal performance in verbal fluency, verbal and visual memories, with greater attention deficits. NMO patients outperformed healthy control in the paced auditory serial addition test (PASAT. However, no difference was found between NMO and RRMS patients. Conclusions: The NMO Group showed more dysfunction in attention and verbal fluencies than in verbal and visual memories. When compared with the MS patients, a similar dysfunction pattern was found. O objetivo da presente pesquisa foi investigar o padrão cognitivo de pacientes com neuromielite óptica (NMO e compará-lo com o desempenho de pacientes com esclerose múltipla (EM. Métodos: Quatorze pacientes com NMO, 14 com esclerose múltipla recorrente remitente (EMRR e 14 participantes do Controle saudáveis participaram da presente investigação. As funções neuropsicológicas foram avaliadas com a Bateria Breve de Testes Neuropsicológicos de Rao, Teste Símbolo Digit e a Fluência Semântica. Resultados: Cinquenta e sete por cento dos pacientes com NMO e 42,85% daqueles com EM apresentaram desempenho anormal em pelo menos dois testes cognitivos. O Grupo NMO apresentarou desempenho anormal na fluência verbal e nas memórias visual e verbal, com maiores déficits de atenção. Pacientes com NMO superaram os controles saudáveis em PASAT. No entanto, não foi

  16. Factors affecting bone mineral density in multiple sclerosis patients

    Science.gov (United States)

    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

  17. Insulin resistance in drug naive patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kostić Smiljana

    2017-01-01

    Full Text Available Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS, the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR and reduced insulin sensitivity (IS in untreated patients with MS could play a role in disease progression and degree of functional disability. Methods. The study included 31 patients with relapsing-remitting (RR MS and 14 healthy controls from the same geographic area matched by age, ethnicity and number of smokers. The glucose tolerance, IS, and IR were examined using an oral glucose tolerance test (OGTT and using basal plasma glucose and insulin levels. The functional disability and disease progression were evaluated by the Expanded Disability Status Scale (EDSS and Multiple Sclerosis Severity Score (MSSS. Results. The MS patients tolerated glucose equally well as the healthy controls. Basal concentrations of insulin were significantly higher in the MS group (p < 0.05, as well as insulin plasma level 30 min after oral glucose load (p < 0.01. The patients with MS had significantly higher values of homeostasis model assessment indexes of IR (HOMA-IR (p = 0.027; p = 0.028. The percentage of IS (HOMA2 %S and whole body IS index (ISI Matsuda showed significantly lower values in the MS patients than in the controls (p = 0.005; p = 0.001. The insulinogenic index in the first 30 min of OGTT was significantly higher in MS patients (p = 0.005. The measures of functional disability and MS progression did not correlate significantly with the investigated parameters of IR and IS indexes. Conclusion. This study demonstrates for the first time the existence of hyperinsulinemia, reduced insulin sensitivity and normal glucose tolerance that indicate the initial

  18. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  19. Multiple sclerosis and suicide.

    Science.gov (United States)

    Feinstein, Anthony; Pavisian, Bennis

    2017-06-01

    Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

  20. Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey.

    Science.gov (United States)

    Anens, Elisabeth; Emtner, Margareta; Zetterberg, Lena; Hellström, Karin

    2014-03-10

    There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey - Revised, Exercise Self-Efficacy Scale, Falls-Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active.

  1. 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.

  2. Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

    Science.gov (United States)

    Voortman, Margarete M; Stojakovic, Tatjana; Pirpamer, Lukas; Jehna, Margit; Langkammer, Christian; Scharnagl, Hubert; Reindl, Markus; Ropele, Stefan; Seifert-Held, Thomas; Archelos, Juan-Jose; Fuchs, Siegrid; Enzinger, Christian; Fazekas, Franz; Khalil, Michael

    2017-10-01

    Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). CSF FLC were significantly increased in CIS/MS compared to controls (all p multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

  3. Reactivation of BK polyomavirus in patients with multiple sclerosis receiving natalizumab therapy.

    LENUS (Irish Health Repository)

    Lonergan, Roisin M

    2012-02-01

    Natalizumab therapy in multiple sclerosis has been associated with JC polyomavirus-induced progressive multifocal leucoencephalopathy. We hypothesized that natalizumab may also lead to reactivation of BK, a related human polyomavirus capable of causing morbidity in immunosuppressed groups. Patients with relapsing remitting multiple sclerosis treated with natalizumab were prospectively monitored for reactivation of BK virus in blood and urine samples, and for evidence of associated renal dysfunction. In this cohort, JC and BK DNA in blood and urine; cytomegalovirus (CMV) DNA in blood and urine; CD4 and CD8 T-lymphocyte counts and ratios in peripheral blood; and renal function were monitored at regular intervals. BK subtyping and noncoding control region sequencing was performed on samples demonstrating reactivation. Prior to commencement of natalizumab therapy, 3 of 36 patients with multiple sclerosis (8.3%) had BK viruria and BK reactivation occurred in 12 of 54 patients (22.2%). BK viruria was transient in 7, continuous in 2 patients, and persistent viruria was associated with transient viremia. Concomitant JC and CMV viral loads were undetectable. CD4:CD8 ratios fluctuated, but absolute CD4 counts did not fall below normal limits. In four of seven patients with BK virus reactivation, transient reductions in CD4 counts were observed at onset of BK viruria: these resolved in three of four patients on resuppression of BK replication. No renal dysfunction was observed in the cohort. BK virus reactivation can occur during natalizumab therapy; however, the significance in the absence of renal dysfunction is unclear. We propose regular monitoring for BK reactivation or at least for evidence of renal dysfunction in patients receiving natalizumab.

  4. HLA DRB5*01 Association Survey with Multiple Sclerosis in Khuzestan Province of Iran

    Directory of Open Access Journals (Sweden)

    Tahereh Latifi Pakdehi

    2017-08-01

    Full Text Available Background Multiple sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system (CNS. Although the cause of MS is currently unknown, both genetic and environmental factors have been shown to contribute to the pathogenesis of MS. The human leukocyte antigen (HLA class II alleles DRB1*1501, DRB5*0101, DQA1*0102, DQB1*0602 may have an important genetic effect. However, this is controversial in different population studies. Objectives The aim of this study was to investigate the correlation of HLA DRB5*01 with MS in Khuzestan province. Methods The present case-control study focused on HLA DRB5*01 association in 202 MS patients from Khuzestan. Seventy four point two five percent (74.25% of patients classified as relapsing-remitting and other patients were as primary-progressive, secondary progressive and progressive-relapsing MS. One hundred eighty seven persons that have no any inflammatory diseases investigated as control group. Polymerase chain reaction amplification method was performed to determine the type of HLA with sequence-specific primers (PCR-SSP. The frequencies of the mentioned allele were compared between the patients and control group using SPSS 21 statistical software and the chi square test. Results Twenty- seven point seven two percent (27.72% of patients and 21.39% from the control group were positive with this type of HLA. Conclusions This is the first study that investigate HLA DRB5*01 association with multiple sclerosis patients in Khuzestan. We found that there is no association between HLA DRB5*01 with multiple sclerosis in Khuzestan province (P = 0.148.

  5. Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

    Science.gov (United States)

    Garcia-Martin, Elena; Ara, Jose R; Martin, Jesus; Almarcegui, Carmen; Dolz, Isabel; Vilades, Elisa; Gil-Arribas, Laura; Fernandez, Francisco J; Polo, Vicente; Larrosa, Jose M; Pablo, Luis E; Satue, Maria

    2017-05-01

    To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. Observational and longitudinal study. One hundred patients with relapsing-remitting MS and 50 healthy controls. All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  6. Falls in multiple sclerosis.

    Science.gov (United States)

    Matsuda, Patricia N; Shumway-Cook, Anne; Bamer, Alyssa M; Johnson, Shana L; Amtmann, Dagmar; Kraft, George H

    2011-07-01

    To examine incidence, associated factors, and health care provider (HCP) response to falls in persons with multiple sclerosis (MS). Cross-sectional retrospective design. Community setting. Four hundred seventy-four persons with MS. Mailed survey questionnaire examined incidence, risk factors, and HCP response to falls in persons with MS who were dwelling in the community. Univariate and multiple ordinal regression analysis identified variables associated with single and multiple falls. Falls, causes and perceived reasons for falls, and HCP response. A total of 265 participants (58.2%) reported one or more falls in the previous 6 months, and 58.5% of falls were medically injurious. Trips/slips while walking accounted for 48% of falls. Factors associated with falls included use of a cane or walker (odds ratio [OR] 2.62; 95% confidence interval [CI] 1.66-4.14), income falls; recommended strategies included safety strategies (53.2%), use of gait assistive devices (42.1%), exercise/balance training (22.2%), and home modifications (16.6%). Factors associated with falls in persons with MS are similar to those in other populations with neurologic diseases. Despite the high incidence of falls, fewer than 50% of people with MS receive information about prevention of falls from an HCP. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  7. 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

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    /kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  8. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial

    DEFF Research Database (Denmark)

    Ravnborg, Mads; Sørensen, Per Soelberg; Andersson, Magnus

    2010-01-01

    status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets....... Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained...

  9. [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.

  10. Expression Profile of Long Non-Coding RNAs in Serum of Patients with Multiple Sclerosis.

    Science.gov (United States)

    Santoro, Massimo; Nociti, Viviana; Lucchini, Matteo; De Fino, Chiara; Losavio, Francesco Antonio; Mirabella, Massimiliano

    2016-05-01

    Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) that leads to severe neurological disability. There is an interest in potential biomarkers that could provide information predicting disease activity and progression. Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of various human disorders, such as oncologic, cardiovascular, and neurodegenerative diseases. No studies have so far explored a potential link between lncRNAs and MS pathology. We screened 84 lncRNAs, involved in autoimmunity and human inflammatory response, in the serum of relapsing-remitting MS (RR-MS) patients (n = 12), age-matched controls (n = 12), and in patients with idiopathic inflammatory myopathy (IIM) (n = 12). We used the following criteria for lncRNAs analysis: fold change >2 and p TUG1), and 7SK small nuclear (RN7SK RNA). Literature data showed that NEAT1, TUG1, and RN7SK RNA play an important role in neurodegenerative processes. Our results indicate that these lncRNAs may be involved in MS pathogenesis. Additional experimental data are needed to clarify the molecular mechanisms through which lncRNAs up-regulation may have a role in MS.

  11. Does hippotherapy effect use of sensory information for balance in people with multiple sclerosis?

    Science.gov (United States)

    Lindroth, Jodi L; Sullivan, Jessica L; Silkwood-Sherer, Debbie

    2015-01-01

    This case-series study aimed to determine if there were observable changes in sensory processing for postural control in individuals with multiple sclerosis (MS) following physical therapy using hippotherapy (HPOT), or changes in balance and functional gait. This pre-test non-randomized design study, with follow-up assessment at 6 weeks, included two females and one male (age range 37-60 years) with diagnoses of relapse-remitting or progressive MS. The intervention consisted of twelve 40-min physical therapy sessions which included HPOT twice a week for 6 weeks. Sensory organization and balance were assessed by the Sensory Organization Test (SOT) and Berg Balance Scale (BBS). Gait was assessed using the Functional Gait Assessment (FGA). Following the intervention period, all three participants showed improvements in SOT (range 1-8 points), BBS (range 2-6 points), and FGA (average 4 points) scores. These improvements were maintained or continued to improve at follow-up assessment. Two of the three participants no longer over-relied on vision and/or somatosensory information as the primary sensory input for postural control, suggesting improved use of sensory information for balance. The results indicate that HPOT may be a beneficial physical therapy treatment strategy to improve balance, functional gait, and enhance how some individuals with MS process sensory cues for postural control. Randomized clinical trials will be necessary to validate results of this study.

  12. Diffusion tensor imaging of occult injury of optic radiation following optic neuritis in multiple sclerosis.

    Science.gov (United States)

    Chen, Jiafeng; Zhu, Lijun; Li, He; Lu, Ziwen; Chen, Xin; Fang, Shaokuan

    2016-10-01

    Multiple sclerosis (MS) is easily detected by routine magnetic resonance imaging (MRI). However, it is not possible to detect early or occult lesions in MS by routine MRI, and this may explain the inconsistency between the severity of the lesions found by MRI and the degree of clinical disability of patients with MS. The present study included 10 patients with relapsing-remitting MS and 10 healthy volunteers. Each patient underwent routine 3.0 T MRI, diffusion tensor imaging (DTI), and diffusion tensor tractography (DTT). Optic nerve and optic radiation were analyzed by DTI and DTT. The fractional anisotropy (FA), mean diffusivity (MD), λ // , and λ ┴ values were measured. In the 10 patients with MS, 7 optic nerves were affected, and 13 optic nerves were not affected. Cranial MRI showed that optic nerve thickening and hyperintensity occurred in 2 patients with MS. In the directionally encoded color maps, a hypointensive green signal in the optic nerve was observed in 3 patients with MS. The FA values were significantly lower and the MD, λ // , and λ ┴ values were significantly higher in the affected and unaffected optic nerves and optic radiations in patients with MS in comparison with controls (P0.05). Diffusion tensor imaging is sensitive in the detection of occult injury of the optic nerve and optic radiation following optic neuritis. Diffusion tensor imaging may be a useful tool for the early diagnosis, treatment and management of MS.

  13. Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Maria Di Bari

    2016-11-01

    Full Text Available Multiple sclerosis (MS is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE and butyrylcholinesterase (BuChE. Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD, is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.

  14. Information processing speed and attention in multiple sclerosis: Reconsidering the Attention Network Test (ANT).

    Science.gov (United States)

    Roth, Alexandra K; Denney, Douglas R; Lynch, Sharon G

    2015-01-01

    The Attention Network Test (ANT) assesses attention in terms of discrepancies between response times to items that differ in the burden they place on some facet of attention. However, simple arithmetic difference scores commonly used to capture these discrepancies fail to provide adequate control for information processing speed, leading to distorted findings when patient and control groups differ markedly in the speed with which they process and respond to stimulus information. This study examined attention networks in patients with multiple sclerosis (MS) using simple difference scores, proportional scores, and residualized scores that control for processing speed through statistical regression. Patients with relapsing-remitting (N = 20) or secondary progressive (N = 20) MS and healthy controls (N = 40) of similar age, education, and gender completed the ANT. Substantial differences between patients and controls were found on all measures of processing speed. Patients exhibited difficulties in the executive control network, but only when difference scores were considered. When deficits in information processing speed were adequately controlled using proportional or residualized score, deficits in the alerting network emerged. The effect sizes for these deficits were notably smaller than those for overall information processing speed and were also limited to patients with secondary progressive MS. Deficits in processing speed are more prominent in MS than those involving attention, and when the former are properly accounted for, differences in the latter are confined to the alerting network.

  15. Self-esteem is associated with perceived stress in multiple sclerosis patients.

    Science.gov (United States)

    N Ifantopoulou, Parthena; K Artemiadis, Artemios; Triantafyllou, Nikolaos; Chrousos, George; Papanastasiou, Ioannis; Darviri, Christina

    2015-07-01

    Previous studies have showed that perceived stress (PS) in patients with multiple sclerosis (MS) constitutes an important factor for disease onset, relapse, symptomatology and psychological adjustment. The aim of this pilot cross-sectional study was to examine the role of self-esteem in PS, after controlling for sociodemographical characteristics, depression and personality in MS patients. Sixty-six relapsing-remitting MS patients (66.67% females, mean age of 40 ± 11.1 years old, mean duration of disease 133.6 ± 128.8 months) were studied. Perceived stress, self-esteem, depression and personality type were assessed using self-administered questionnaires. Hierarchical multivariate regression modelling was used. Higher education and depression and lower self-esteem were independently and significantly associated with increased PS, accounting for 40.5% of its variance. Univariate analyses revealed that low extroversion and openness and higher neurotism were associated with higher PS, although no significant after adjusting for other factors. Although our findings need further confirmation, psychological interventions targetting self-esteem are strongly encouraged.

  16. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, M. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Department of Radiology, Medical School, University of Minnesota, MN(United States); Tali, T.; Isik, S. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Kocer, B. [Department of Neurology, Gazi University Medical School, Ankara (Turkey)

    2000-12-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  17. From Leflunomide to Teriflunomide: Drug Development and Immunosuppressive Oral Drugs in the Treatment of Multiple Sclerosis.

    Science.gov (United States)

    Aly, Lilian; Hemmer, Bernhard; Korn, Thomas

    2017-01-01

    Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, orally available second generation immunosuppressive agents have been approved or are filed for licensing as MS therapeutics. Due to semi-selective targeting of cellular processes, these second-generation immunosuppressive compounds might rather be immunomodulatory. For example, Teriflunomide inhibits the de novo pyrimidine synthesis and thus only targets rapidly proliferating cells, including lymphocytes. It is used as first line disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Review of online content related to oral immunosuppressants in MS with an emphasis on Teriflunomide. Teriflunomide and Cladribine are second-generation immunosuppressants that are efficient in the treatment of MS patients. For Teriflunomide, a daily dose of 14 mg reduces the annualized relapse rate (ARR) by more than 30% and disability progression by 30% compared to placebo. Cladribine reduces the ARR by about 50% compared to placebo but has not yet been licensed due to unresolved safety concerns. We also discuss the significance of older immunosuppressive compounds including Azathioprine, Mycophenolate mofetile, and Cyclophosphamide in current MS therapy. Teriflunomide has shown a favorable safety and efficacy profile in RRMS and is a therapeutic option for a distinct group of adult patients with RRMS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

    Science.gov (United States)

    Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

    2014-09-01

    Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (ptreatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

  19. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    Science.gov (United States)

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  20. Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

    Science.gov (United States)

    Zipoli, V; Portaccio, E; Siracusa, G; Pracucci, G; Sorbi, S; Amato, M P

    2003-10-01

    We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

  1. Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.

    Science.gov (United States)

    Dineen, Robert A; Bradshaw, Christopher M; Constantinescu, Cris S; Auer, Dorothee P

    2012-01-01

    Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, Pvisual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, Precall in MS patients with mild memory dysfunction.

  2. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bettina Kuenz

    Full Text Available BACKGROUND: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS, relapsing-remitting (RR and chronic progressive (CP MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138- and plasma blasts (CD19+CD138+ in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP-9 and the B cell chemokine CxCL-13. CONCLUSIONS: Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS.

  3. 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.

  4. Molecular Profiling of Glatiramer Acetate Early Treatment Effects in Multiple Sclerosis

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    Achiron, Anat; Feldman, Anna; Gurevich, Michael

    2009-01-01

    Background: Glatiramer acetate (GA, Copaxone®) has beneficial effects on the clinical course of relapsing-remitting multiple sclerosis (RRMS). However, the exact molecular mechanisms of GA effects are only partially understood. Objective: To characterized GA molecular effects in RRMS patients within 3 months of treatment by microarray profiling of peripheral blood mononuclear cells (PBMC). Methods: Gene-expression profiles were determined in RRMS patients before and at 3 months after initiation of GA treatment using Affimetrix (U133A-2) microarrays containing 14,500 well-characterized human genes. Most informative genes (MIGs) of GA-induced biological convergent pathways operating in RRMS were constructed using gene functional annotation, enrichment analysis and pathway reconstruction bioinformatic softwares. Verification at the mRNA and protein level was performed by qRT-PCR and FACS. Results: GA induced a specific gene expression molecular signature that included altered expression of 480 genes within 3 months of treatment; 262 genes were up-regulated, and 218 genes were down-regulated. The main convergent mechanisms of GA effects were related to antigen-activated apoptosis, inflammation, adhesion, and MHC class-I antigen presentation. Conclusions: Our findings demonstrate that GA treatment induces alternations of immunomodulatory gene expression patterns that are important for suppression of disease activity already at three months of treatment and can be used as molecular markers of GA activity. PMID:19893201

  5. Identification of targets and new developments in the treatment of multiple sclerosis – focus on cladribine

    Directory of Open Access Journals (Sweden)

    Clemens Warnke

    2010-06-01

    Full Text Available Clemens Warnke1, Heinz Wiendl2, Hans-Peter Hartung1, Olaf Stüve3, Bernd C Kieseier11Department of Neurology, Heinrich-Heine University Düsseldorf, Germany; 2Department of Neurology – Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Germany; 3Department of Neurology, Dallas VA Medical Center and UT Southwestern Medical Center, Dallas, Texas, USAAbstract: Orally available disease-modifying drugs for relapsing-remitting multiple sclerosis (MS represent an unmet need for this chronic and debilitating disease. Among 5 currently investigated drugs at phase 3 clinical stage, promising efficacy data for fingolimod and oral cladribine have recently been published. However, benefits need to be weighed against the risks to define the role of these compounds within current treatment regimens. In this review, data on the efficacy of a promising compound, oral cladribine, are discussed and balanced with known and anticipated risks in a postmarketing era, and finally gives an outlook on the potential place of this drug in treatment algorithms for MS in the future.Keywords: immunosuppressant, oral drugs, risk–benefit, safety

  6. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    International Nuclear Information System (INIS)

    Teksam, M.; Tali, T.; Isik, S.; Kocer, B.

    2000-01-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  7. Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis.

    Science.gov (United States)

    Tauhid, Shahamat; Chu, Renxin; Sasane, Rahul; Glanz, Bonnie I; Neema, Mohit; Miller, Jennifer R; Kim, Gloria; Signorovitch, James E; Healy, Brian C; Chitnis, Tanuja; Weiner, Howard L; Bakshi, Rohit

    2015-11-01

    Multiple sclerosis (MS) commonly affects occupational function. We investigated the link between brain MRI and employment status. Patients with MS (n = 100) completed a Work Productivity and Activity Impairment (WPAI) (general health version) survey measuring employment status, absenteeism, presenteeism, and overall work and daily activity impairment. Patients "working for pay" were considered employed; "temporarily not working but looking for work," "not working or looking for work due to age," and "not working or looking for work due to disability" were considered not employed. Brain MRI T1 hypointense (T1LV) and T2 hyperintense (T2LV) lesion volumes were quantified. To assess lesional destructive capability, we calculated each subject's ratio of T1LV to T2LV (T1/T2). Normalized brain parenchymal volume (BPV) assessed brain atrophy. The mean (SD) age was 45.5 (9.7) years; disease duration was 12.1 (8.1) years; 75 % were women, 76 % were relapsing-remitting, and 76 % were employed. T1LV, T1/T2, Expanded Disability Status Scale (EDSS) scores, and activity impairment were lower and BPV was higher in the employed vs. not employed group (Wilcoxon tests, p 0.05). In multivariable logistic regression modeling, adjusting for age, sex, and disease duration, higher T1LV predicted a lower chance of employment (p 0.05). We report a link between brain atrophy and lesions, particularly lesions with destructive potential, to MS employment status.

  8. In-person and online social participation and emotional health in individuals with multiple sclerosis.

    Science.gov (United States)

    Sparling, Alica; Stutts, Lauren A; Sanner, Haley; Eijkholt, Marleen M

    2017-11-01

    Individuals with multiple sclerosis (MS) sometimes have barriers to social participation. The advent of the internet has created online support systems for social participation such as websites for individuals with MS. However, minimal research has been conducted about determinants of individuals' in-person and online social participation or how types of social participation contribute to emotional well-being. The present study aims are: (1) to assess the role of access to resources and other determinants as enabling in-person and online social participation, and (2) to analyze the association between social participation and emotional health of individuals with MS. The sample consisted of 508 individuals diagnosed with relapsing/remitting or secondary/progressive MS. Data from NARCOMS registry and data from original questionnaire on determinants of social participation and emotional health were merged. Logistic and linear regression analyses were performed. Individuals with access to the internet were more likely to participate online with friends (OR 5.47, p social participation with friends reported being happier (B = .38, p health and online social participation. Increasing access to in-person social participation with friends will likely have the most positive impact on emotional health. Future research should examine the aspects of online participation that are helpful or harmful.

  9. Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study.

    Science.gov (United States)

    Schwartz, Carolyn E; Ayandeh, Armon; Ramanathan, Murali; Benedict, Ralph; Dwyer, Michael G; Weinstock-Guttman, Bianca; Zivadinov, Robert

    2015-08-12

    Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve-building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. There were group differences in past and current reserve-building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve-building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle-modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities.

  10. Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

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    Carrubba, Simona; Minagar, Alireza; Chesson, Andrew L; Frilot, Clifton; Marino, Andrew A

    2012-04-01

    Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

  11. Thalamic lesions in multiple sclerosis by 7T MRI: Clinical implications and relationship to cortical pathology.

    Science.gov (United States)

    Harrison, Daniel M; Oh, Jiwon; Roy, Snehashis; Wood, Emily T; Whetstone, Anna; Seigo, Michaela A; Jones, Craig K; Pham, Dzung; van Zijl, Peter; Reich, Daniel S; Calabresi, Peter A

    2015-08-01

    Pathology in both cortex and deep gray matter contribute to disability in multiple sclerosis (MS). We used the increased signal-to-noise ratio of 7-tesla (7T) MRI to visualize small lesions within the thalamus and to relate this to clinical information and cortical lesions. We obtained 7T MRI scans on 34 MS cases and 15 healthy volunteers. Thalamic lesion number and volume were related to demographic data, clinical disability measures, and lesions in cortical gray matter. Thalamic lesions were found in 24/34 of MS cases. Two lesion subtypes were noted: discrete, ovoid lesions, and more diffuse lesional areas lining the periventricular surface. The number of thalamic lesions was greater in progressive MS compared to relapsing-remitting (mean ±SD, 10.7 ±0.7 vs. 3.0 ±0.7, respectively, p < 0.001). Thalamic lesion burden (count and volume) correlated with EDSS score and measures of cortical lesion burden, but not with white matter lesion burden or white matter volume. Using 7T MRI allows identification of thalamic lesions in MS, which are associated with disability, progressive disease, and cortical lesions. Thalamic lesion analysis may be a simpler, more rapid estimate of overall gray matter lesion burden in MS. © The Author(s), 2015.

  12. Agreement analysis comparing iPad LCVA and Sloan testing in multiple sclerosis patients.

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    Sattarnezhad, Neda; Farrow, Samantha; Kimbrough, Dorlan; Glanz, Bonnie; Healy, Brian; Chitnis, Tanuja

    2017-06-01

    Visual symptoms are common in multiple sclerosis (MS). Low-contrast visual acuity (LCVA) testing using Sloan charts has demonstrated increased sensitivity for visual deficits compared to high-contrast acuity testing. Computerized testing of visual acuity may facilitate use in the clinic setting. To evaluate the agreement between an iPad-based and Sloan testing of LCVA in a cohort of MS patients. A total of 38 patients with relapsing-remitting MS were enrolled after providing informed written consent at Partners MS Center, Brigham and Women's hospital. Monocular LCVA was measured using retroilluminated Sloan chart and iPad-based LogMAR chart. Number of correct letters and agreement between two measurements were assessed for each eye using Bland-Altman analysis and paired t-test. For both eyes, there was no significant difference in number correct between the two measurements using a paired t-test, and there was high correlation between two measurements (oculus dextrus (OD) r = 0.89, p iPad-based LCVA test shows good agreement with Sloan testing in MS patients.

  13. Application of diffusional kurtosis imaging to detect occult brain damage in multiple sclerosis and neuromyelitis optica.

    Science.gov (United States)

    Qian, Wenshu; Chan, Koon Ho; Hui, Edward S; Lee, Chi Yan; Hu, Yong; Mak, Henry Ka-Fung

    2016-11-01

    Multiple sclerosis (MS) and neuromyelitis optica (NMO) are two common types of inflammatory demyelinating disease of the central nervous system. Early distinction of NMO from MS is crucial but quite challenging. In this study, 13 NMO spectrum disorder patients (Expanded Disability Status Scale (EDSS) of 3.0 ± 1.7, ranging from 2 to 6.5; disease duration of 5.3 ± 4.7 years), 17 relapsing-remitting MS patients (EDSS of 2.6 ± 1.4, ranging from 1 to 5.5; disease duration of 7.9 ± 7.8 years) and 18 healthy volunteers were recruited. Diffusional kurtosis imaging was employed to discriminate NMO and MS patients at the early or stable stage from each other, and from healthy volunteers. The presence of alterations in diffusion and diffusional kurtosis metrics in normal-appearing white matter (NAWM) and diffusely increased mean diffusivity (MD) in the cortical normal-appearing gray matter (NAGM) favors the diagnosis of MS rather than NMO. Meanwhile, normal diffusivities and kurtosis metrics in all NAWM as well as increases in MD in the frontal and temporal NAGM suggest NMO. Our results suggest that diffusion and diffusional kurtosis metrics may well aid in discriminating the two diseases. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Vitamin D3 supplementation in multiple sclerosis: Symptoms and biomarkers of depression.

    Science.gov (United States)

    Rolf, Linda; Muris, Anne-Hilde; Bol, Yvonne; Damoiseaux, Jan; Smolders, Joost; Hupperts, Raymond

    2017-07-15

    Depressive symptoms are common in multiple sclerosis (MS), and both depression and MS have been associated with a poor vitamin D status. As cytokine-mediated inflammatory processes play a role in the pathogenesis of both disorders, we hypothesized that vitamin D 3 supplementation reduces depressive symptoms in MS via its immunomodulatory properties. In this randomized pilot study relapsing remitting (RR) MS patients received either vitamin D 3 supplementation (n=20; 14.000IU/day) or placebo (n=20) during 48weeks. Pre- and post-supplementation depression scores, measured using the Hospital Anxiety Depression Scale (HADS) depression subscale (HADS-D), showed a significant decrease within the vitamin D 3 group (median HADS-D 4.0 to 3.0, p=0.02), a trend towards a decrease within the placebo group (median HADS-D 3.0 to 2.0, p=0.06), but no significantly different reductions between groups (p=0.78). Furthermore, no reductions in pro- and anti-inflammatory cytokine balances, secreted by stimulated leukocytes and CD8 + T cells, were found in the vitamin D 3 compared to the placebo arm. Therefore, we found no evidence for a reduction of depressive symptoms or related biomarkers upon vitamin D 3 supplementation in RRMS patients in this exploratory study. Whether vitamin D 3 supplementation is of benefit in manifest depression in MS needs to be assessed by additional studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.

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    Timucin Avsar

    Full Text Available Multiple sclerosis (MS is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179. Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5 which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5 system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10 pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5. An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.

  16. Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

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    Bastianello Stefano

    2011-10-01

    Full Text Available Abstract Background Chronic cerebrospinal venous insufficiency (CCSVI has recently been reported to be associated with multiple sclerosis (MS. However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian. All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients. Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity.

  17. Quantifying Gait Impairment Using an Instrumented Treadmill in People with Multiple Sclerosis

    Science.gov (United States)

    Kalron, Alon; Dvir, Zeevi; Frid, Lior; Achiron, Anat

    2013-01-01

    Background and Objective. Treadmill gait analysis has been proposed as an attractive alternative for overground walking measuring systems. The purpose of this study was twofold: first to determine spatiotemporal parameters of treadmill gait in patients with multiple sclerosis (MS) and second to examine whether these parameters are associated with specific functional impairments in this cohort. Method. Eighty-seven relapsing-remitting patients diagnosed with MS, 50 women and 37 men, aged 40.9 ± 11.9 with an expanded disability status scale (EDSS) score of 2.7 ± 1.6, participated in this study. Twenty-five apparently healthy subjects, 14 women and 11 men, aged 38.5 ± 9.4, served as controls. Spatiotemporal gait parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). People with MS demonstrated significantly shorter steps, extended stride time, wider base of support, longer step time, reduced single support phase, and a prolonged double support phase compared to the healthy controls. The EDSS score was significantly correlated with all spatiotemporal gait parameters. Conclusion. The instrumented treadmill may be an effective tool in assessing ambulation capabilities of people with MS. PMID:23878746

  18. Depressive Symptoms in Multiple Sclerosis from an In Vivo Study with TBSS

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    Yujuan Shen

    2014-01-01

    Full Text Available Clinically significant depression can impact up to 50% of patients with multiple sclerosis (MS over a course of their life time, which is associated with an increased morbidity and mortality. In our study, fifteen relapsing-remitting MS (RRMS patients and 15 age- and gender-matched normal controls were included. Diffusion tensor imaging (DTI was acquired by employing a single-shot echo planar imaging sequence on a 3.0 T MR scanner and fractional anisotropy (FA was performed with tract-based spatial statistics (TBSS approach. Finally, widespread WM and GM abnormalities were observed in RRMS patients. Moreover, the relationships between the depressive symptoms which can be measured by Hamilton depression rating scale (HAMD as well as clinical disabilities measured by the expanded disability status scale (EDSS and FA changes were listed. There was a positive relation between EDSS and the FA changes in the right inferior parietal lobule, while negative relation was located in the left anterior cingulate cortex and hippocampus. Also a positive relation between HAMD and FA changes was found in the right posterior middle cingulate gyrus, the right hippocampus, the left hypothalamus, the right precentral gyrus, and the posterior cingulate which demonstrated a link between the depressive symptoms and clinically relevant brain areas in RRMS patients.

  19. Multiple sclerosis decreases explicit counterfactual processing and risk taking in decision making.

    Science.gov (United States)

    Simioni, Samanta; Schluep, Myriam; Bault, Nadège; Coricelli, Giorgio; Kleeberg, Joerg; Du Pasquier, Renaud A; Gschwind, Markus; Vuilleumier, Patrik; Annoni, Jean-Marie

    2012-01-01

    Deficits in decision making (DM) are commonly associated with prefrontal cortical damage, but may occur with multiple sclerosis (MS). There are no data concerning the impact of MS on tasks evaluating DM under explicit risk, where different emotional and cognitive components can be distinguished. We assessed 72 relapsing-remitting MS (RRMS) patients with mild to moderate disease and 38 healthy controls in two DM tasks involving risk with explicit rules: (1) The Wheel of Fortune (WOF), which probes the anticipated affects of decisions outcomes on future choices; and (2) The Cambridge Gamble Task (CGT) which measures risk taking. Participants also underwent a neuropsychological and emotional assessment, and skin conductance responses (SCRs) were recorded. In the WOF, RRMS patients showed deficits in integrating positive counterfactual information (paffect than controls (disappointment: p = 0.007; regret: p = 0.01), although their implicit emotional reactions as measured by post-choice SCRs did not differ. In the CGT, RRMS patients differed from controls in quality of DM (p = 0.01) and deliberation time (p = 0.0002), the latter difference being correlated with attention scores. Such changes did not result in overall decreases in performance (total gains). The quality of DM under risk was modified by MS in both tasks. The reduction in the expression of disappointment coexisted with an increased risk aversion in the WOF and alexithymia features. These concomitant emotional alterations may have implications for better understanding the components of explicit DM and for the clinical support of MS patients.

  20. Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

    Science.gov (United States)

    Heidker, Rebecca M; Emerson, Mitchell R; LeVine, Steven M

    2016-12-01

    While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.

  1. MRI outcomes with cladribine tablets for multiple sclerosis in the CLARITY study.

    Science.gov (United States)

    Comi, Giancarlo; Cook, Stuart D; Giovannoni, Gavin; Rammohan, Kottil; Rieckmann, Peter; Sørensen, Per Soelberg; Vermersch, Patrick; Hamlett, Anthony C; Viglietta, Vissia; Greenberg, Steven J

    2013-04-01

    We herein provide a comprehensive assessment of magnetic resonance imaging (MRI) outcomes from CLARITY, a 96-week, double-blind study demonstrating significant clinical and MRI improvements in patients with relapsing-remitting multiple sclerosis (RRMS) treated with cladribine tablets. Patients with RRMS were randomized 1:1:1 to annual short-course therapy with cladribine tablets cumulative dose 3.5 or 5.25 mg/kg or placebo. MRI endpoints included mean number of T1 gadolinium-enhancing (Gd+), active T2 and combined unique (CU) lesions/patient/scan. MRI-measured disease activity was significantly reduced in both cladribine tablets groups versus placebo. The proportion of patients with no active lesions at study end was: T1 Gd+ lesions: 86.8 and 91.0 versus 48.3 % (p tablet groups when data were stratified by baseline disease characteristics. For example, the percentage of patients who remained lesion-free over the study was significantly greater in cladribine tablet groups than in the placebo group for all lesion types regardless of relapse category at baseline (p MRI-measured disease activity was greatly reduced by both doses of cladribine tablets, with consistent effect across clinically relevant patient populations. These findings add to our scientific understanding of the neurological impact of this therapeutic modality in patients with RRMS.

  2. Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects

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    Deepali Mathur

    2017-12-01

    Full Text Available Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS. In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s expression and suggest that MS appears to be linked with metabolic deformity.

  3. Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

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    Jonas Bergquist

    2012-06-01

    Full Text Available Multiple Sclerosis (MS is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject.

  4. Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

    Science.gov (United States)

    Füvesi, Judit; Hanrieder, Jörg; Bencsik, Krisztina; Rajda, Cecilia; Kovács, S. Krisztián; Kaizer, László; Beniczky, Sándor; Vécsei, László; Bergquist, Jonas

    2012-01-01

    Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. PMID:22837721

  5. Superior temporal gyrus thickness correlates with cognitive performance in multiple sclerosis.

    Science.gov (United States)

    Achiron, Asaf; Chapman, Joab; Tal, Sigal; Bercovich, Eran; Gil, Hararai; Achiron, Anat

    2013-07-01

    Decreased cortical thickness that signifies gray matter pathology and its impact on cognitive performance is a research field with growing interest in relapsing-remitting multiple sclerosis (RRMS) and needs to be further elucidated. Using high-field 3.0 T MRI, three-dimensional T1-FSPGR (voxel size 1 × 1 × 1 mm) cortical thickness was measured in 82 regions in the left hemisphere (LH) and right hemisphere (RH) in 20 RRMS patients with low disease activity and in 20 age-matched healthy subjects that in parallel underwent comprehensive cognitive evaluation. The correlation between local cortical atrophy and cognitive performance was examined. We identified seven regions with cortical tissue loss that differed between RRMS and age-matched healthy controls. These regions were mainly located in the frontal and temporal lobes, specifically within the gyrus rectus, inferior frontal sulcus, orbital gyrus, parahippocampal gyrus, and superior temporal gyrus, with preferential left asymmetry. Increased cortical thickness was identified in two visual sensory regions, the LH inferior occipital gyrus, and the RH cuneus, implicating adaptive plasticity. Correlation analysis demonstrated that only the LH superior temporal gyrus thickness was associated with cognitive performance and its thickness correlated with motor skills (r = 0.65, p = 0.003), attention (r = 0.45, p = 0.042), and information processing speed (r = 0.50, p = 0.025). Our findings show that restricted cortical thinning occurs in RRMS patients with mild disease and that LH superior temporal gyrus atrophy is associated with cognitive dysfunction.

  6. Changes in gross grasp strength and fine motor skills in adolescents with pediatric multiple sclerosis.

    Science.gov (United States)

    Squillace, Mary; Ray, Sharon; Milazzo, Maria

    2015-01-01

    This study examined the gross grasp strength and fine motor dexterity of adolescents, who are diagnosed with multiple sclerosis (MS). A total sample size of 72 participants between the ages of 13 to 17 was studied. Thirty six with a diagnosis of pediatric relapse remitting MS and 36 matched control participants were selected from various local youth groups. Data on hand strength and dexterity was collected using a dynamometer, nine hole peg board and Purdue pegboard on both groups. Utilizing ANCOVA to describe the differences across the two groups by diagnosis, controlling for age and gender, it was found that the MS group demonstrated significantly decreased dexterity when compared to age and gender matched controls. There was no significant difference in gross grasp strength by diagnostic group. This preliminary study showed that children with a diagnosis of pediatric MS may have differences in fine motor dexterity, but not gross grasp strength from their peers who do not have the diagnosis. Further study is indicated to examine this phenomenon.

  7. Albumin and multiple sclerosis.

    Science.gov (United States)

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  8. 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

  9. 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....

  10. 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...

  11. 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...

  12. 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

  13. [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.

  14. Electrophysiological Evaluation of Dysphagia in the Mild or Moderate Patients with Multiple Sclerosis: A Concept of Subclinical Dysphagia.

    Science.gov (United States)

    Beckmann, Yesim; Gürgör, Nevin; Çakır, Ahmet; Arıcı, Şehnaz; İncesu, Tülay Kurt; Seçil, Yaprak; Ertekin, Cumhur

    2015-06-01

    Swallowing mechanism and neurogenic dysphagia in MS have been rarely studied by electromyographical (EMG) methods. This study aims to evaluate the presence of subclinical dysphagia in patients with mild multiple sclerosis (MS) using electrophysiological methods. A prospective study of 51 patients with relapsing remitting multiple sclerosis and 18 age-matched healthy adults was investigated. We used electromyography to measure the activity of the submental muscles during swallowing. Electrophysiological recordings of patients were obtained during relapse, after relapse, and at any time in remission period. Clinical dysphagia was found in 12% of MS patients, while electrophysiological swallowing abnormalities were encountered in 33% of patients. Subclinical dysphagia was determined in 35% of patients during an MS relapse, in 20% of patients after a relapse, and in 25% of all 51 patients in the remission period based on EMG findings. Duration of swallowing signal of submental muscles in all MS patients was found to be longer than in normal subjects (p = 0.001). During swallowing of 50 ml of sequential water, the compensatory respiratory cycles occurred more often in MS patients than normal subjects, especially during a relapse (p = 0.005). This is the first study investigating swallowing abnormalities and subclinical dysphagia from the electrophysiological aspect in MS patients with mild disability. The electrophysiological tests described in this study are useful to uncover subclinical dysphagia since they have the advantage of being rapid, easy to apply, non-invasive, and without risk for the patients.

  15. Viruses and Multiple Sclerosis

    Science.gov (United States)

    Virtanen, Jussi Oskari; Jacobson, Steve

    2016-01-01

    Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents. PMID:22583435

  16. High-intensity resistance training in multiple sclerosis - An exploratory study of effects on immune markers in blood and cerebrospinal fluid, and on mood, fatigue, health-related quality of life, muscle strength, walking and cognition.

    Science.gov (United States)

    Kierkegaard, Marie; Lundberg, Ingrid E; Olsson, Tomas; Johansson, Sverker; Ygberg, Sofia; Opava, Christina; Holmqvist, Lotta Widén; Piehl, Fredrik

    2016-03-15

    High-intensity resistance training is unexplored in people with multiple sclerosis. To evaluate effects of high-intensity resistance training on immune markers and on measures of mood, fatigue, health-related quality of life, muscle strength, walking and cognition. Further, to describe participants' opinion and perceived changes of the training. Twenty patients with relapsing-remitting multiple sclerosis performed high-intensity resistance training at an intensity of 80% of one-repetition maximum, twice a week for 12 weeks. Blood and optional cerebrospinal fluid samples, and data on secondary outcome measures were collected before and after intervention. A study-specific questionnaire was used for capturing participants' opinion. Seventeen participants completed the study. Plasma cytokine levels of tumor necrosis factor were significantly decreased post-intervention (p=0.001). Exploratory cytokine analyses in cerebrospinal fluid (n=8) did not reveal major changes. Significant and clinically important improvements were found in fatigue (p=0.001) and health-related quality of life (p=0.004). Measures of mood (p=0.002), muscle strength (p ≤ 0.001), walking speed (p=0.013) and cognition (p=0.04) were also improved. A majority of participants evaluated the training as very good and perceived changes to the better. High-intensity resistance training in persons with relapsing remitting multiple sclerosis with low disability had positive effects on peripheral pro-inflammatory cytokine levels, led to clinically relevant improvements in measures of fatigue and health-related quality of life, and was well tolerated. These results provide a basis for a larger randomized trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial.

    Science.gov (United States)

    Leist, Thomas P; Comi, Giancarlo; Cree, Bruce A C; Coyle, Patricia K; Freedman, Mark S; Hartung, Hans-Peter; Vermersch, Patrick; Casset-Semanaz, Florence; Scaramozza, Matthew

    2014-03-01

    Patients who develop relapsing-remitting multiple sclerosis (MS) present with a first clinical demyelinating event. In this double-blind, multicentre, randomised, phase 3 study we investigated the effect of oral cladribine on conversion to clinically definite MS in patients with a first clinical demyelinating event, when given at the same doses shown to be effective in relapsing-remitting MS. Between Oct 21, 2008, and Oct 11, 2010, we recruited patients aged 18-55 years, inclusive, from 160 hospitals, private clinics, or treatment centres in 34 countries. Eligible patients had a first clinical demyelinating event within 75 days before screening, at least two clinically silent lesions of at least 3 mm on a T2-weighted brain MRI scan, and an Expanded Disability Status Scale score of 5.0 or lower. Patients with a first clinical demyelinating event ≤75 days before screening were randomly assigned (1:1:1) to receive cladribine tablets at cumulative doses of 5.25 mg/kg or 3.5 mg/kg or placebo. Randomisation was done with a central web-based randomisation system and was stratified by geographic region. Masking was maintained using a two-physician model. The primary endpoint of this 96-week study was time to conversion to clinically definite MS according to the Poser criteria. This study is registered with ClinicalTrials.gov, number NCT00725985. Of 903 participants assessed for eligibility, 616 patients received cladribine 5.25 mg/kg (n=204), cladribine 3.5 mg/kg (n=206), or placebo (n=206). At trial termination on Oct 25, 2011, cladribine was associated with a risk reduction versus placebo for time to conversion to clinically definite MS (hazard ratio [HR] for 5.25 mg/kg=0.38, 95% CI 0.25-0.58, pMS diagnosis compared with placebo. The safety profile of cladribine was similar to that noted in a trial in patients with relapsing-remitting MS. Further research could clarify the potential effects of oral cladribine treatment in the early stages of MS. Merck Serono SA Geneva

  18. Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Elskamp, I.J. van den; Boden, B.; Barkhof, F. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); Dattola, V. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); University of Messina, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina (Italy); Knol, D.L. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Filippi, M. [Scientific Institute and University Ospedale San Raffaele, Neuroimaging Research Unit, Milan (Italy); Kappos, L. [University Hospital, University of Basel, Department of Neurology, Basel (Switzerland); Fazekas, F. [Medical University of Graz, Department of Neurology, Graz (Austria); Wagner, K. [Bayer-Schering Pharma, Berlin (Germany); Pohl, C. [Bayer-Schering Pharma, Berlin (Germany); University Hospital Bonn, Department of Neurology, Bonn (Germany); Sandbrink, R. [Bayer-Schering Pharma, Berlin (Germany); Heinrich-Heine-University Dusseldorf, Department of Neurology, Dusseldorf (Germany); Polman, C.H. [VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands); Uitdehaag, B.M.J. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands)

    2010-10-15

    Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. (orig.)

  19. Midkine and multiple sclerosis.

    Science.gov (United States)

    Takeuchi, Hideyuki

    2014-02-01

    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 development of Treg and DCreg leads to the development of autoimmune diseases. However, the factors that regulate Treg and DCreg are largely unknown. We recently showed that removal of midkine (MK) suppressed EAE due to an expansion of the Treg cell population as well as a decrease in the numbers of autoreactive Th1 and Th17 cells. MK decreased the Treg cell population by suppressing the phosphorylation of STAT5, which is essential for the expression of Foxp3, the master transcriptional factor of Treg cell differentiation. Furthermore, MK reduces the DCreg cell population by inhibiting the phosphorylation of STAT3, which is critical for DCreg development. Blockade of MK signalling by a specific RNA aptamer significantly elevated the population of DCreg and Treg cells and ameliorated EAE without detectable adverse effects. Therefore, the inhibition of MK may provide an effective therapeutic strategy against autoimmune diseases including MS. This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4. © 2013 The British Pharmacological Society.

  20. Analyzing clinical symptoms in multiple sclerosis using data mining

    Directory of Open Access Journals (Sweden)

    Zahra Raeisi

    2017-04-01

    Full Text Available Background: One of the today most common and incurable diseases that is associated with central neural system is ‘MS’ disease. Multiple sclerosis (MS is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. In this disease become apparent a wide spectrum of symptoms such as lose muscles control and their coordination and vision derangement. The goal of this research is to consider to two problems: 1- Recognition of effective clinical symptoms on MS disease and 2- Considering levels of effectiveness of age, sex and education levels factors on MS disease and association between these factors according to verity of categories of this disease. Methods: Data mining science in medicine is worthy of attention with main application in diagnosis, therapy and prognosis, respectively high volume of collected datum. The data that were used in this article are about patients of Chaharmahal and Bakhtiari Province and collected by cure assistance. In this paper classification and association methods in software engineering field are used. Classification is a general process related to categorization, the process in which ideas and objects are recognized, differentiated, and understood. Association rules are created by analyzing data for frequent if/then patterns and using the criteria support and confidence to identify the most important relationships. Results: In consideration of first problem in this paper, concluded vision-clinical symptoms are the most effective symptoms and in consideration of second problem, concluded that from 584 records, women affected four times more than men. In other word 70% of MS patients with high graduate are in relapsing-remitting category and 62.5% of MS patients are 20-40 years old. Conclusion: Some of symptoms are quite temporary and transitory and are ignored by people. Awareness of clinical-symptoms prevalence manner can be warning for people before starting

  1. Efficacy of group cognitive rehabilitation therapy in multiple sclerosis.

    Science.gov (United States)

    Mani, A; Chohedri, E; Ravanfar, P; Mowla, A; Nikseresht, A

    2018-06-01

    Cognitive impairment occurs in 40%-65% of patients with multiple sclerosis (MS). Several techniques for cognitive rehabilitation (CR) in these patients have been evaluated; however, the results have been controversial. In this study, we investigated the efficacy of group compensatory CR in patients with MS-related cognitive impairment. Thirty-four female patients with diagnosed relapsing-remitting MS and evidence of impaired cognitive function were included and randomized to intervention (n = 17) and control (n = 17) groups. CR intervention consisted of eight 2-hour sessions of comprehensive group CR over a 4-week period that focused on improvement of memory, attention, and executive function. As placebo, the control group received the same number of non-therapeutic group sessions. Assessment of cognitive function was performed before intervention (pretest), at the end of intervention (post-test), and 3 months later (follow-up). The study population included 34 patients with a mean age of 35.5 years. Statistical comparison of memory assessments at 3-month follow-up showed significantly higher scores in the CR group than in the control group (93.33 vs 86.40 for Addenbrooke's Cognitive Examination test and 16.58 vs 12.00 for visual memory, 19.32 vs 14.05 for verbal memory, and 51.28 vs 44.41 for general scores on the Memory Functioning Questionnaire test, respectively). Wisconsin card sorting test score comparison showed significantly lower total time consumption in the CR group than in the control group (308.1 vs 340.8 seconds, respectively). Behavior rating inventory of executive function-adult scores in all four subtests were significantly higher in the CR group than in the control group (40.25 vs 55.4 for behavioral regulation index, 51.16 vs 68.6 for metacognition index, and 97.41 vs 124.00 for global executive composite, respectively). Attention was the only domain in which we did not observe any significant variation between groups in terms of post

  2. [Epidemiological aspects of multiple sclerosis in Lublin (Poland)].

    Science.gov (United States)

    Łobińska, Alicja; Stelmasiak, Zbigniew

    2004-01-01

    The objective of this paper was to present an epidemiological analysis of multiple sclerosis (MS) in Lublin, identify MS prevalence as well as characterize the population of MS patients. Information about the patients was gathered and they were examined from 1996 to the end of 2000, that is within a 5-year period. The patients' data were obtained from the neurological departments in Lublin, most often neurological (but also general and ophthalmic) clinics, as well as from the Lublin MS Society. The remaining patients' data were obtained from the doctors, family members, the Lublin MS Society members, as well as from the hospital and clinic files. The patients were interviewed in detail using a prepared questionnaire. The diagnosis and its degree of certainty were determined in accordance with the Poser's criteria. The control group included 111 healthy people who were Lublin residents on the day of examination. The obtained results were analyzed in epidemiological and statistical terms. On the prevalence day (31 December 1997) there were 204 MS cases in Lublin, including 141 women (69%) and 63 men (31%). The calculated incidence ratio was 57.3/105. The average age of MS onset was estimated to be 30.1 years. On 31 December 1997 the average duration of the illness was 15.4 years. The average age for the examined cases was 45.5 years. The average DSS (Disability Status Scale) score was 3.5. Most often the disease began with a single symptom, in 155 cases (75.9%), whereas several symptoms occurred in 37 patients (18.1%). The most common symptoms at the illness onset were sensory impairments (52 patients), optic neuritis (42 people) and pyramidal symptoms (34 patients). The most common form of the illness was a disseminated form, which was diagnosed in 131 patients (64.2%). In the examined patient population four types of MS were recognized. The relapsing-remitting MS (RR-MS) was observed in 62 patients (30.3%), the secondary progressive MS (SP-MS) in 83 patients (40

  3. CYTOKINES AND HERPESVIRUSES IN CHILDREN WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    G. F. Zheleznikova

    2015-01-01

    Full Text Available It was determined earlier (G.P. Ivanova, 2012 that a chronic course of leukoencephalitis in teenagers caused by inadequate response of cytokine system to the combination of two herpesviruses (HV — EBV and HHV-6, leads to the development of multiple sclerosis (MS in 44% of cases. The research objective was to characterize the cytokine response in children with MS with simultaneous screening of the presence of active HV infections. 39 children with the diagnosis “MS” were under observation, 34 of them had relapsing-remitting (RR MS, and 5 children had a progressing course of MS (PMS. Concentration of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ, and IL-4 was identified in blood serum and cerebrospinal liquid (CSF by enzyme-linked immunosorbent assay, HV DNA was revealed by PCR. Cytokine status in children with MS had some differences depending on the phase of the disease, clinical severity of the relapse and the course of MS. The relapse phase of RRMS was associated with the accumulation of IL-8, IL-10, and IL-6 in the blood, and index IFNγ/IL-4 modulations in accordance with the clinical severity of the relapse. A severe aggravation of the disease in children with PMS was accompanied by the increase of IL-8 system response. HV DNA was revealed in 27 patients from 39 ones (69% in blood and in 17 patients (44% in CSF with the predominance of EBV (93%, frequently in combination with HHV-6. During an acute period the frequency of HV DNA identification increased 2–3 times to compare with the remission period. Unlike children with RRMS, a mixed-infection of 3–4 herpes viruses was revealed in all 5 patients with PMS. According to the results summary it is possible to make a conclusion that HV-infection has an important role in MS pathogenesis in teenagers, taking part in the aggravation and progression of the disease by its effect on the cytokine system response. EBV-infection dominates among HV, however the risk of MS development

  4. Effects of prolonged fasting on fatigue and quality of life in patients with multiple sclerosis.

    Science.gov (United States)

    Etemadifar, Masoud; Sayahi, Farnaz; Alroughani, Raed; Toghianifar, Nafiseh; Akbari, Mojtaba; Nasr, Zahra

    2016-06-01

    Fasting is one of the recommended worships of several great religions in the world. During the month of Ramadan, circadian rhythm and pattern of eating changes result in physiological, biochemical and hormonal changes in the body. Many Muslims with medical conditions ask their physicians about the feasibility and safety of fasting during Ramadan. In this study, we aim to assess the effect of Ramadan fasting on the quality of life and fatigue in multiple sclerosis (MS) patients. Relapsing-remitting MS (RRMS) patients according to McDonald's criteria who had mild disability (EDSS score ≤3) were included in this study. Fatigue and quality of life were were assessed using the validated Persian versions of modified fatigue impact scale (MFIS) and multiple sclerosis quality of life-54 (MSQOL-54) questionnaires, respectively. 218 patients (150 females and 68 males) were enrolled in our study. There was no statistically significant difference between the mean total score of MSIF before and after fasting (25.50 ± 13.81 versus 26.94 ± 16.65; p = 0.58). The mean physical health and mental health composites of quality of life increased significantly after fasting (p = 0.008 and p = 0.003 respectively). Despite the observed lack of favorable effects on fatigue, our results showed increased quality of life of MS patients once Ramadan has ended. Whether this is specifically related to Ramadan-related fasting deserves further testing in appropriately designed larger prospective clinical studies.

  5. Prevalence of Multiple Sclerosis in the Metropolitan Area of Edirne City, Turkey

    Directory of Open Access Journals (Sweden)

    Yahya Çelik

    2011-06-01

    Full Text Available Objective: The prevalence and incidence of multiple sclerosis may vary according to the influence of the altitude of a geographical area as well as the genetic and environmental factors. This study ained to determine the incidence and prevalence of multiple sclerosis in Edirne population.Material and Methods: Patients with a definite diagnosis of MS according to McDonald’s criteria, admitted to one of the three MS clinics in Edirne, were included in this two-stage study. Also the records of hospitals in İstanbul serving patients from Edirne, have been evaluated. Results: The prevalence rate of confirmed MS patients was 33.9/100000 (95% CI: 32-36 in 2003. The mean annual incidence was 3.48/100000 (95% CI: 2.90-4.00. Mean age of the patients was 36.5±9.6 years. Mean age at onset was 29.2±8.5 years. Mean duration of disease was 6.9±5.2 years. Overall, 69.2% had a relapsing-remitting course, 20.5% had a primary progressive course and 10.3% had a secondary progressive course. Mean Expanded Disability Status Scale score was 3.04±2.18. The prevalence and annual incidence after one year was 36.5 per 100000 (95% CI: 33.2-38.6 and 2.60 per 100000 (95% CI: 2.1-3.8, respectively.Conclusion: This is the first city-based MS prevalence study performed in Turkey. The MS prevalence in Edirne is similar to that of Greece and Bulgaria but lower than that of European countries.

  6. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sowa, Piotr [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Owren Nygaard, Gro [Oslo University Hospital, Department of Neurology, Oslo (Norway); Bjoernerud, Atle [Intervention Center, Oslo University Hospital, Oslo (Norway); University of Oslo, Department of Physics, Oslo (Norway); Gulowsen Celius, Elisabeth [Oslo University Hospital, Department of Neurology, Oslo (Norway); University of Oslo, Institute of Health and Society, Faculty of Medicine, Oslo (Norway); Flinstad Harbo, Hanne [University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo (Norway); Oslo University Hospital, Department of Neurology, Oslo (Norway); Kristiansen Beyer, Mona [Oslo University Hospital, Department of Radiology and Nuclear Medicine, Oslo (Norway); Oslo and Akershus University College of Applied Sciences, Department of Life Sciences and Health, Oslo (Norway)

    2017-07-15

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  7. Magnetic resonance imaging perfusion is associated with disease severity and activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Sowa, Piotr; Owren Nygaard, Gro; Bjoernerud, Atle; Gulowsen Celius, Elisabeth; Flinstad Harbo, Hanne; Kristiansen Beyer, Mona

    2017-01-01

    The utility of perfusion-weighted imaging in multiple sclerosis (MS) is not well investigated. The purpose of this study was to compare baseline normalized perfusion measures in subgroups of newly diagnosed MS patients. We wanted to test the hypothesis that this method can differentiate between groups defined according to disease severity and disease activity at 1 year follow-up. Baseline magnetic resonance imaging (MRI) including a dynamic susceptibility contrast perfusion sequence was performed on a 1.5-T scanner in 66 patients newly diagnosed with relapsing-remitting MS. From the baseline MRI, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were generated. Normalized (n) perfusion values were calculated by dividing each perfusion parameter obtained in white matter lesions by the same parameter obtained in normal-appearing white matter. Neurological examination was performed at baseline and at follow-up approximately 1 year later to establish the multiple sclerosis severity score (MSSS) and evidence of disease activity (EDA). Baseline normalized mean transit time (nMTT) was lower in patients with MSSS >3.79 (p = 0.016), in patients with EDA (p = 0.041), and in patients with both MSSS >3.79 and EDA (p = 0.032) at 1-year follow-up. Baseline normalized cerebral blood flow and normalized cerebral blood volume did not differ between these groups. Lower baseline nMTT was associated with higher disease severity and with presence of disease activity 1 year later in newly diagnosed MS patients. Further longitudinal studies are needed to confirm whether baseline-normalized perfusion measures can differentiate between disease severity and disease activity subgroups over time. (orig.)

  8. Optimization and stratification of multiple sclerosis treatment in fast developing economic countries: a perspective from Qatar.

    Science.gov (United States)

    Deleu, Dirk; Mesraoua, Boulenouar; El Khider, Hisham; Canibano, Beatriz; Melikyan, Gayane; Al Hail, Hassan; Mhjob, Noha; Bhagat, Anjushri; Ibrahim, Faiza; Hanssens, Yolande

    2017-03-01

    The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS that conform to the healthcare system in a fast-developing economic country such as Qatar. We conducted a systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane Database of Systematic Reviews (1 January 1990 through 30 September 2016). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites to obtain relevant safety information on these DMTs. For each of the DMTs, the mode of action, efficacy, safety and tolerability are briefly discussed. To facilitate the interpretation, the efficacy data of the pivotal phase III trials are expressed by their most clinically useful measure of therapeutic efficacy, the number needed to treat (NNT). In addition, an overview of head-to-head trials in RRMS is provided as well as a summary of the several different RRMS management strategies (lateral switching, escalation, induction, maintenance and combination therapy) and the potential role of each DMT. Finally, algorithms were developed for CIS, active and highly active or rapidly evolving RRMS and subsequent breakthrough disease or suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the DMTs, taking into account patient preference, allowed the provision of rational and safe patient-tailored treatment algorithms. Recommendations and algorithms for the management of CIS and RRMS have been developed relevant to the

  9. "THE RELATION OF HYPERHOMOCYSTEINEMIA TO COGNITIVE FUNCTION AND BRAIN ATROPHY IN PATIENTS WITH MULTIPLE SCLEROSIS "

    Directory of Open Access Journals (Sweden)

    M. Ghaffarpour

    2007-06-01

    Full Text Available Cognitive impairment may be a common even at the onset of multiple sclerosis (MS. In this case-control study, we tried to find out the probable relationship between homocysteine levels and cerebral atrophy or cognitive impairment in patients with multiple sclerosis. One hundred fifty six patients who had MS according to McDonald diagnostic criteria were included in this study. Patients’ age, gender, and educational level, MS duration and clinical type, disability, cognitive function state based on minimental state examination (MMSE, presence of hyperhomocysteinemia, and brain atrophy were evaluated. There was no statistically significant relationship between hyperhomocysteinemia and cognitive status. Total homocysteine levels had a significant correlation with MMSE score only in those patients with elementary level of education. Also total homocysteine levels and overall cerebral atrophy did not indicate significant relationship according to those independent variables mentioned above except in the patients with EDSS less than 6. When intercaudate ratio > 0.10 was applied as a criterion for cerebral atrophy, we found that hyperhomocysteinemia related significantly to intercaudate ratio > 0.10 in females, aged between 21 and 30 years, MS duration ≤ 5 years, primary progressive MS and relapsing-remitting MS clinical types, EDSS ≤ 3 and elementary level of education. We suggest applying MMSE only for the first step of cognitive function survey. In the next steps, much more exact test must be used (e.g. MSNQ. Also we can not suggest measuring plasma homocysteine level as criterion for monitoring the cognitive function in patients with MS.

  10. Employment and absenteeism in working-age persons with multiple sclerosis.

    Science.gov (United States)

    Salter, Amber; Thomas, Nina; Tyry, Tuula; Cutter, Gary; Marrie, Ruth Ann

    2017-05-01

    To better understand the impact of the clinical course of multiple sclerosis (MS) and disability on employment, absenteeism, and related factors. This study included respondents to the North American Research Committee on Multiple Sclerosis Registry spring 2015 update survey who were US or Canadian residents, aged 18-65 years and reported having relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). The RRMS and SPMS participants were combined to form the relapsing-onset MS (RMS) group and compared with the PPMS group regarding employment status, absenteeism, and disability. Multivariable logistic regression was used to examine the relationship between employment-related outcomes and factors that may affect these relationships. Of the 8004 survey respondents, 5887 (73.6%) were 18-65 years of age. The PPMS group (n = 344) had a higher proportion of males and older mean age at the time of the survey and at time of diagnosis than the RMS group (n = 4829). Female sex, age, age at diagnosis, cognitive and hand function impairment, fatigue, higher disability levels, ≥3 comorbidities, and a diagnosis of PPMS were associated with not working. After adjustment for disability, the employed PPMS sub-group reported similar levels of absenteeism to the employed RMS sub-group. Limitations of the study include self-report of information and the possibility that participants may not fully represent the working-age MS population. In MS, employment status and absenteeism are negatively affected by disability, cognitive impairment, and fatigue. These findings underscore the need for therapies that prevent disability progression and other symptoms that negatively affect productivity in persons with MS to enable them to persist in the workforce.

  11. Nurse-led immunotreatment DEcision Coaching In people with Multiple Sclerosis (DECIMS) - Feasibility testing, pilot randomised controlled trial and mixed methods process evaluation.

    Science.gov (United States)

    Rahn, A C; Köpke, S; Backhus, I; Kasper, J; Anger, K; Untiedt, B; Alegiani, A; Kleiter, I; Mühlhauser, I; Heesen, C

    2018-02-01

    Treatment decision-making is complex for people with multiple sclerosis. Profound information on available options is virtually not possible in regular neurologist encounters. The "nurse decision coach model" was developed to redistribute health professionals' tasks in supporting immunotreatment decision-making following the principles of informed shared decision-making. To test the feasibility of a decision coaching programme and recruitment strategies to inform the main trial. Feasibility testing and parallel pilot randomised controlled trial, accompanied by a mixed methods process evaluation. Two German multiple sclerosis university centres. People with suspected or relapsing-remitting multiple sclerosis facing immunotreatment decisions on first line drugs were recruited. Randomisation to the intervention (n = 38) or control group (n = 35) was performed on a daily basis. Quantitative and qualitative process data were collected from people with multiple sclerosis, nurses and physicians. We report on the development and piloting of the decision coaching programme. It comprises a training course for multiple sclerosis nurses and the coaching intervention. The intervention consists of up to three structured nurse-led decision coaching sessions, access to an evidence-based online information platform (DECIMS-Wiki) and a final physician consultation. After feasibility testing, a pilot randomised controlled trial was performed. People with multiple sclerosis were randomised to the intervention or control group. The latter had also access to the DECIMS-Wiki, but received otherwise care as usual. Nurses were not blinded to group assignment, while people with multiple sclerosis and physicians were. The primary outcome was 'informed choice' after six months including the sub-dimensions' risk knowledge (after 14 days), attitude concerning immunotreatment (after physician consultation), and treatment uptake (after six months). Quantitative process evaluation data

  12. 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 ...

  13. 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 ...

  14. 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...

  15. 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...

  16. 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

  17. 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...

  18. 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...

  19. 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

  20. 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

  1. Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Kantor, Daniel; Johnson, Kristen; Vieira, Maria Cecilia; Signorovitch, James; Li, Nanxin; Gao, Wei; Koo, Valerie; Duchesneau, Emilie; Herrera, Vivian

    2018-05-15

    To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I 2  = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS. Copyright © 2018. Published by Elsevier B.V.

  2. 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.

  3. Relevance of brain lesion location to cognition in relapsing multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Francesca Rossi

    Full Text Available OBJECTIVE: To assess the relationship between cognition and brain white matter (WM lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS. METHODS: MRI-based T2 lesion probability map (LPM was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP and cognitively impaired (CI. RESULTS: Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001, T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major than in CP patients (37% in the posterior corona radiata. The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected. Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions. CONCLUSIONS: Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.

  4. 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

  5. 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.

  6. 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 ...

  7. Knee flexor strength and balance control impairment may explain declines during prolonged walking in women with mild multiple sclerosis.

    Science.gov (United States)

    Ramari, Cintia; Moraes, Andréa G; Tauil, Carlos B; von Glehn, Felipe; Motl, Robert; de David, Ana C

    2018-02-01

    Physiological factors such as muscle weakness and balance could explain declines in walking distance by multiple sclerosis (MS) patients. The purpose of this study was to characterize levels and examine associations among decline in walking distance, balance and muscular strength in women with mild MS. Participants included 28 women with mild relapsing-remitting MS and 21 women without MS. We executed the 6-min walk test (6MWT) to verify declines in walking distance. Isokinetic knee flexion (KF) and extension (KE) muscle strength was measured using a dynamometer. Balance was quantified using a force platform, with eyes open and closed, on a rigid and foam surface. The MS patients presented declines in walking, lower KF muscle strength, and worse balance than controls. KF strength and balance correlated with walking in the MS group. The KF strength explained differences between groups in walking. The KF strength and balance presented as predictors of walking slowing down in the 6MWT, in mild MS. Women with mild MS have strength impairment of knee flexor muscles and balance control impairment that may explain walking related motor fatigability during prolonged walking. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Impaired information processing speed and attention allocation in multiple sclerosis patients versus controls: a high-density EEG study.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    BACKGROUND: The no-go P3a is a variant of the P300 event-related potential (ERP) that indexes speed of information processing and attention allocation. The aim of this study was to compare ERP findings with results from the paced auditory serial addition test (PASAT) and to quantify latency, amplitude and topographical differences in P3a ERP components between multiple sclerosis (MS) patients and controls. PATIENTS AND METHODS: Seventy-four subjects (20 relapsing remitting (RRMS) patients, 20 secondary progressive (SPMS) patients and 34 controls) completed a three-stimulus oddball paradigm (target, standard, and non-target). Subjects participated in separate visual and auditory tasks while data were recorded from 134 EEG channels. Latency differences were tested using an ANCOVA. Topographical differences were tested using statistical parametric mapping. RESULTS: Visual P3a amplitude correlated with PASAT score in all MS patients over frontal and parietal areas. There were significant differences in latency, amplitude, and topography between MS patients and controls in the visual condition. RRMS and SPMS patients differed in visual P3a latency and amplitude at frontal and parietal scalp regions. In the auditory condition, there were latency differences between MS patients and controls only over the parietal region. CONCLUSION: The present results demonstrate that information processing speed and attention allocation are impaired in MS.

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

    Science.gov (United States)

    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.

  10. Lack of magnetic resonance imaging lesion activity as a treatment target in multiple sclerosis: An evaluation using electronically collected outcomes.

    Science.gov (United States)

    Conway, Devon S; Thompson, Nicolas R; Cohen, Jeffrey A

    2016-09-01

    The appropriate treatment target in multiple sclerosis (MS) is unclear. Lack of magnetic resonance imaging (MRI) lesion activity, a component of the no evidence of disease activity concept, has been proposed as a treatment target in MS. We used our MS database to investigate whether aggressively pursuing MRI stability by changing disease modifying therapy (DMT) when MRI activity is observed leads to better clinical and imaging outcomes. The Knowledge Program (KP) is a database linked to our electronic medical record allowing capture of patient and clinician reported outcomes. Through KP query and chart review, we identified all relapsing-remitting MS patients visiting between 1 January 2008 and 31 December 2014 with active MRIs despite DMT. Propensity modeling based on demographic and disease characteristics was used to match DMT switchers to non-switchers. KP and MRI outcomes were compared 18 months after the active MRI using mixed-effects linear regression models. We identified 417 patients who met criteria for our analysis. After propensity matching, 78 switchers and 91 non-switchers were analyzed. There was no difference in clinical or radiologic outcomes between these groups at 18 months. We did not find a short-term benefit of changing DMT to pursue MRI stability. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Influence of multiple sclerosis, age and degree of disability, in the position of the contrast sensitivity curve peak

    Directory of Open Access Journals (Sweden)

    A F Nunes

    2014-01-01

    Full Text Available Context: Contrast sensitivity (CS function is one of the most important tests available for evaluating visual impairment. Multiple sclerosis (MS can produce highly selective losses in visual function and psychophysical studies have demonstrated CS deficits for some spatial frequencies. Aims: This work studies the differences in CS between a group of controls and a group of MS patients, focusing on the location of the maximum sensitivity peak, shape of the curve, and determination of the most affected spatial frequencies. Materials and Methods: Using a sinusoidal stimulus the authors assessed CS function in 28 subjects with definitive relapsing remitting MS, and in 50 controls with acuities of 20/25 or better. The peaks of the CS curves were studied by fitting third degree polynomials to individual sets of data. Results: Compared with the control group, the CS function curve for MS subjects showed more deficits in extreme points (low- and high-spatial frequencies. Our results display significant CS losses, at the high-frequencies band level, in the beginning of the disease. When the disease progresses and the disabilities appear, there are greater losses at the low-frequencies band level. In average, the CS curve peaks for the MS group were shifted in relation to the control group. Conclusions: CS losses in the MS group suggest an association with ageing and disability level in the expanded disability status scale. The position of the CS function peak is influenced by MS, age, and degree of disability.

  12. A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

  13. Modulation of the Left Prefrontal Cortex with High Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Gait in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Amer M. Burhan

    2015-01-01

    Full Text Available Multiple Sclerosis (MS is a chronic central nervous system (CNS demyelinating disease. Gait abnormalities are common and disabling in patients with MS with limited treatment options available. Emerging evidence suggests a role of prefrontal attention networks in modulating gait. High-frequency repetitive transcranial magnetic stimulation (rTMS is known to enhance cortical excitability in stimulated cortex and its correlates. We investigated the effect of high-frequency left prefrontal rTMS on gait parameters in a 51-year-old Caucasian male with chronic relapsing/remitting MS with residual disabling attention and gait symptoms. Patient received 6 Hz, rTMS at 90% motor threshold using figure of eight coil centered on F3 location (using 10-20 electroencephalography (EEG lead localization system. GAITRite gait analysis system was used to collect objective gait measures before and after one session and in another occasion three consecutive daily sessions of rTMS. Two-tailed within subject repeated measure t-test showed significant enhancement in ambulation time, gait velocity, and cadence after three consecutive daily sessions of rTMS. Modulating left prefrontal cortex excitability using rTMS resulted in significant change in gait parameters after three sessions. To our knowledge, this is the first report that demonstrates the effect of rTMS applied to the prefrontal cortex on gait in MS patients.

  14. Different types of exercise in Multiple Sclerosis: Aerobic exercise or Pilates, a single-blind clinical study.

    Science.gov (United States)

    Kara, Bilge; Küçük, Fadime; Poyraz, Esra Coşkuner; Tomruk, Melda Soysal; İdıman, Egemen

    2017-01-01

    The aim of our study is to examine effects of aerobic and Pilates exercises on disability, cognition, physical performance, balance, depression and fatigue in relapsing-remitting Multiple Sclerosis (MS) patients as compared to healthy controls. The subjects were divided as aerobic exercise (n = 26), Pilates (n = 9), and the healthy control group (n = 21). We used MSFC, physical performance, Berg balance scale, Beck depression scale, fatigue impact scale. All evaluations were performed before and after exercise training. There are statistically meaningful differences between Nine hole testing, PASAT 3, physical performance and fatique impact scale before and after aerobic exercise. Also we found significant difference for physical performance in the Pilates group. There are no significant differences in measures of fatique impact scale and depression between aerobic exercise group and the healthy controls after exercise. We found significant differences between Pilates and control group's after measurements except depression. There were significant differences between the Pilates and aerobic group for cognitive tests in favor of the Pilates group. Aerobic exercise and clinical Pilates exercises revealed moderate changes in levels of cognitive, physical performance, balance, depression, fatigue in MS patients.

  15. An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis

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    Yabe Ichiro

    2002-08-01

    Full Text Available Abstract Background The Apo-1/Fas (CD95 molecule is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor (TNF receptor family. Both Fas and Fas ligand (FasL are expressed in activated mature T cells, and prolonged cell activation induces susceptibility to Fas-mediated apoptosis. The Apo-1/Fas gene is located in a chromosomal region that shows linkage in multiple sclerosis (MS genome screens, and studies indicate that there is aberrant expression of the Apo-1/Fas molecule in MS. Methods Mva I polymorphism on the Apo-1/Fas promoter gene was detected by PCR-RFLP from the DNA of 114 Japanese patients with conventional MS and 121 healthy controls. We investigated the association of the Mva I polymorphism in Japanese MS patients using a case-control association study design. Results We found no evidence that the polymorphism contributes to susceptibility to MS. Furthermore, there was no association between Apo-1/Fas gene polymorphisms and clinical course (relapsing-remitting course or secondary-progressive course. No significant association was observed between Apo-1/Fas gene polymorphisms and the age at disease onset. Conclusions Overall, our findings suggest that Apo-1/Fas promoter gene polymorphisms are not conclusively related to susceptibility to MS or the clinical characteristics of Japanese patients with MS.

  16. No relevant impact of ambient temperature on disability measurements in a large cohort of patients with multiple sclerosis.

    Science.gov (United States)

    Stellmann, J-P; Young, K L; Vettorazzi, E; Pöttgen, J; Heesen, C

    2017-06-01

    Many patients with multiple sclerosis (MS) report a worsening of symptoms due to high ambient temperatures, but objective data about this association are rare and contradictory. The aim of this study was to investigate the influence of ambient temperature on standard clinical tests. We extracted the Symbol Digit Modality Test, Nine Hole Peg Test, Timed 25 Foot Walk (T25FW), Timed Tandem Walk, Expanded Disability Status Scale (EDSS) and quality-of-life items on cognition, fatigue and depression from our clinical database and matched them to historical temperatures. We used linear mixed-effect models to investigate the association between temperature and outcomes. A total of 1254 patients with MS (mean age, 42.7 years; 69.9% females; 52.1% relapsing-remitting MS, mean EDSS, 3.8) had 5751 assessments between 1996 and 2012. We observed a worsening in the T25FW with higher ambient temperatures in moderately disabled patients (EDSS ≥ 4) but not in less disabled patients. However, an increase of 10°C prolonged the T25FW by just 0.4 s. Other outcomes were not associated with ambient temperatures. Higher ambient temperature might compromise walking capabilities in patients with MS with a manifest walking impairment. However, effects are small and not detectable in mildly disabled patients. Hand function, cognition, mood and fatigue do not appear to be correlated with ambient temperature. © 2017 EAN.

  17. Metabolic Changes in the Visual Cortex Are Linked to Retinal Nerve Fiber Layer Thinning in Multiple Sclerosis

    Science.gov (United States)

    Schubert, Florian; Bock, Markus; Walaszek, Bernadeta; Waiczies, Helmar; Schwenteck, Thomas; Dörr, Jan; Bellmann-Strobl, Judith; Mohr, Christian; Weinges-Evers, Nicholetta; Ittermann, Bernd; Wuerfel, Jens T.; Paul, Friedemann

    2011-01-01

    Objective To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients' clinical symptoms concerning the visual pathway. Design, Subjects and Methods Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter. Results RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA. This was connected with the patients' history of a previous optic neuritis. In a combined model, both BPF and visual cortex NAA were independently associated with RNFLT. Conclusions Our data suggest the existence of functional pathway-specific damage patterns exceeding global neurodegeneration. They suggest a strong interrelationship between damage to the anterior and the posterior visual pathway. PMID:21494672

  18. Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J.; Nicoli, F.; Gastaut, J.L.

    1996-01-01

    We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple sclerosis (MS), 12 patients with degenerative dementia and 17 control patients using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at 400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased lactate and fructose concentrations, decreased creatinine and phenylalanine concentrations) and is not correlated with the intensity of the intrathecal inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and primary progressive MS. We have not detected any specific abnormal resonance in native or lyophilized CSF. The CSF metabolic profile of demented patients is much more altered (increased concentration of lactate, pyruvate, alanine, lysine, valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain oxidative metabolism impairment as already described in Alzheimer's disease. Unassigned abnormal but non specific or constant resonances have been detected on MR spectra of demented patients. CSF inositol concentration is also increased in the CSF of patients with Alzheimer's disease. In vitro high resolution proton MRS of the CSF constitutes a new and original way to explore CSF for the differential and/or early diagnosis of dementias, as a complement to in vivo proton cerebral MRS. (authors). 22 refs., 4 figs., 2 tabs

  19. Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France); Nicoli, F. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)]|[Hopital Sainte-Marguerite, 13 - Marseille (France); Gastaut, J.L. [Hopital Sainte-Marguerite, 13 - Marseille (France)

    1996-07-01

    We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple sclerosis (MS), 12 patients with degenerative dementia and 17 control patients using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at 400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased lactate and fructose concentrations, decreased creatinine and phenylalanine concentrations) and is not correlated with the intensity of the intrathecal inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and primary progressive MS. We have not detected any specific abnormal resonance in native or lyophilized CSF. The CSF metabolic profile of demented patients is much more altered (increased concentration of lactate, pyruvate, alanine, lysine, valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain oxidative metabolism impairment as already described in Alzheimer`s disease. Unassigned abnormal but non specific or constant resonances have been detected on MR spectra of demented patients. CSF inositol concentration is also increased in the CSF of patients with Alzheimer`s disease. In vitro high resolution proton MRS of the CSF constitutes a new and original way to explore CSF for the differential and/or early diagnosis of dementias, as a complement to in vivo proton cerebral MRS. (authors). 22 refs., 4 figs., 2 tabs.

  20. One-Dimensional-Ratio Measures of Atrophy Progression in Multiple Sclerosis as Evaluated by Longitudinal Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Martola, J.; Wiberg Kristoffersen, M.; Aspelin, P.; Stawiarz, L.; Fredrikson, S.; Hillert, J.; Bergstroem, J.; Flodmark, O.

    2009-01-01

    Background: For decades, normalized one-dimensional (1D) measures have been used in the evaluation of brain atrophy. In multiple sclerosis (MS), the use of normalized linear measures over longitudinal follow-up remains insufficiently documented. Purpose: To evaluate the association between different regional atrophy measures and disability in MS patients over four decades in a longitudinal cross-sectional study. Material and Methods: 37 consecutively selected MS patients were included. At baseline, patients had a range of disease duration (1-33 years) and age (24-65 years). Each patient was followed by magnetic resonance imaging (MRI) for a mean of 9.25 years (range 7.3-10 years). Four 1D measures were applied at three time points on axial 5-mm T1-weighted images. Three clinical MS subgroups were represented: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). Results: There were significant changes in all 1D ratios during follow-up. The Evans ratio (ER) and the bifrontal ratio (BFR) were associated with the development of disability. Changes of ER and BFR reflected more aggressive disease progression, as expressed by MS severity score (MSSS). Conclusion: All four normalized ratios showed uniform atrophy progression, suggesting a consistent rate of atrophy over long-term disease duration independent of MS course. Disability status correlated with 1D measures, suggesting that serial evaluation of Evans and bifrontal ratios might contribute to the radiological evaluation of MS patients

  1. Thrombin generation correlates with disease duration in multiple sclerosis (MS): Novel insights into the MS-associated prothrombotic state.

    Science.gov (United States)

    Parsons, Martin Em; O'Connell, Karen; Allen, Seamus; Egan, Karl; Szklanna, Paulina B; McGuigan, Christopher; Ní Áinle, Fionnuala; Maguire, Patricia B

    2017-01-01

    Thrombin is well recognised for its role in the coagulation cascade but it also plays a role in inflammation, with enhanced thrombin generation observed in several inflammatory disorders. Although patients with multiple sclerosis (MS) have a higher incidence of thrombotic disease, thrombin generation has not been studied to date. The aim of this study was to characterise calibrated automated thrombography parameters in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) in comparison to healthy controls (HCs). Calibrated automated thrombography was performed on platelet poor plasma from 15 patients with RRMS, 15 with PPMS and 19 HCs. We found that patients with RRMS generate thrombin at a significantly faster rate than the less inflammatory subtype, PPMS or HCs. In addition, the speed of thrombin generation was significantly correlated with time from clinical diagnosis in both subtypes. However, in RRMS the rate of thrombin generation was increased with increased time from clinical diagnosis, while in PPMS the rate of thrombin generation decreased with increased time from clinical diagnosis. These data likely reflect the differential active proinflammatory states in each MS subtype and provide novel mechanistic insights into the clinically relevant prothrombotic state observed in these patients.

  2. Functional Components of Cognitive Impairment in Multiple Sclerosis: A Cross-Sectional Investigation

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    Jordi A. Matias-Guiu

    2017-11-01

    Full Text Available BackgroundCognitive impairment is frequent and disabling in multiple sclerosis (MS. Changes in information processing speed constitute the most important cognitive deficit in MS. However, given the clinical and topographical variability of the disease, cognitive impairment may vary greatly and appear in other forms in addition to slower information processing speed. Our aim was to determine the frequency of cognitive impairment, the principal cognitive domains, and components involved in MS and to identify factors associated with presence of cognitive impairment in these patients in a large series of patients.MethodsCross-sectional study of 311 patients with MS [236 with relapsing-remitting MS (RRMS, 52 with secondary progressive MS (SPMS, and 23 with primary progressive MS (PPMS]. Patients’ cognitive function was assessed with a comprehensive neuropsychological assessment protocol. Patients displaying deficits in 2 or more cognitive domains were considered to have cognitive impairment associated with MS. We conducted a principal component analysis to detect different cognitive patterns by identifying clusters of tests highly correlated to one another.ResultsCognitive impairment was detected in 41.5% of the sample, and it was more frequent in patients with SPMS and PPMS (P = 0.002. Expanded Disability Status Scale scores and education were independent predictors of cognitive impairment. Principal component analysis identified seven clusters: attention and basic executive function (including information processing speed, planning and high-level executive function, verbal memory and language, executive and visuospatial performance time, fatigue-depression, visuospatial function, and basic attention and verbal/visual working memory. Mean scoring of components 2 (high-order executive functioning and 3 (verbal memory-language was higher in patients with RRMS than in those with PPMS (component 2 and SPMS (component 3.ConclusionMS is linked to

  3. Cardiovascular risk factors are associated with increased lesion burden and brain atrophy in multiple sclerosis.

    Science.gov (United States)

    Kappus, Natalie; Weinstock-Guttman, Bianca; Hagemeier, Jesper; Kennedy, Cheryl; Melia, Rebecca; Carl, Ellen; Ramasamy, Deepa P; Cherneva, Mariya; Durfee, Jacqueline; Bergsland, Niels; Dwyer, Michael G; Kolb, Channa; Hojnacki, David; Ramanathan, Murali; Zivadinov, Robert

    2016-02-01

    Cardiovascular (CV) risk factors have been associated with changes in clinical outcomes in patients with multiple sclerosis (MS). To investigate the frequency of CV risks in patients with MS and their association with MRI outcomes. In a prospective study, 326 patients with relapsing-remitting MS and 163 patients with progressive MS, 61 patients with clinically isolated syndrome (CIS) and 175 healthy controls (HCs) were screened for CV risks and scanned on a 3T MRI scanner. Examined CV risks included hypertension, heart disease, smoking, overweight/obesity and type 1 diabetes. MRI measures assessed lesion volumes (LVs) and brain atrophy. Association between individual or multiple CV risks and MRI outcomes was examined adjusting for age, sex, race, disease duration and treatment status. Patients with MS showed increased frequency of smoking (51.7% vs 36.5%, p = 0.001) and hypertension (33.9% vs 24.7%, p=0.035) compared with HCs. In total, 49.9% of patients with MS and 36% of HCs showed ≥ 2 CV risks (p = 0.003), while the frequency of ≥ 3 CV risks was 18.8% in the MS group and 8.6% in the HCs group (p = 0.002). In patients with MS, hypertension and heart disease were associated with decreased grey matter (GM) and cortical volumes (p < 0.05), while overweight/obesity was associated with increased T1-LV (p < 0.39) and smoking with decreased whole brain volume (p = 0.049). Increased lateral ventricle volume was associated with heart disease (p = 0.029) in CIS. Patients with MS with one or more CV risks showed increased lesion burden and more advanced brain atrophy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Natural history of multiple sclerosis from the Indian perspective: Experience from a tertiary care hospital.

    Science.gov (United States)

    Jena, Subhransu S; Alexander, Mathew; Aaron, Sanjith; Mathew, Vivek; Thomas, Maya Mary; Patil, Anil K; Sivadasan, Ajith; Muthusamy, Karthik; Mani, Sunithi; Rebekah, J Grace

    2015-01-01

    Multiple sclerosis (MS) has a spectrum of heterogeneity, as seen in western and eastern hemispheres, in the clinical features, topography of involvement and differences in natural history. To study the clinical spectrum, imaging, and electrophysiological as well as cerebrospinal fluid (CSF) characteristics and correlate them with outcome. Retrospective analysis of MS patients during a period of 20 years. Cases were selected according to recent McDonald's criteria (2010), They were managed in the Department of Neurology, Christian Medical College, Vellore. Chi-square and Fisher's exact tests were used for categorical variables. Multiple binary logistic regressions were done to assess significance. Kaplan-Meier curves were drawn to estimate the time to irreversible disability. A total of 157 patients with female preponderance (55%) were included. The inter quartile range duration of follow-up was 9.1 (8.2, 11) years for 114 patients, who were included for final outcome analysis. Relapsing remitting MS (RRMS) (54.1%) was the most common type of MS seen. RRMS had a significantly better outcome (odds ratio: 0.12, 95% confidence interval: 0.02-0.57, P = 0.008) compared to progressive form of MS (primary progressive, secondary progressive). The Expanded Disability Status Scale score of patients at presentation and at final follow-up was 4.4 ± 1.31 and 4.1 ± 2.31, respectively. During the first presentation, polysymptomatic manifestations like motor and sphincteric involvement, incomplete recovery from the first attack; and, during the disease course, bowel, bladder, cerebellar and pyramidal affliction, predicted a worse outcome. A high incidence of optico-spinal presentation, predominance of RRMS and a low yield on cerebrospinal fluid (CSF) studies are the major findings of our study. A notable feature was the analysis of prognostic markers of disability.

  5. Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

    Science.gov (United States)

    Kolbe, Scott C; Kilpatrick, Trevor J; Mitchell, Peter J; White, Owen; Egan, Gary F; Fielding, Joanne

    2014-05-01

    Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Copyright © 2013 Wiley Periodicals, Inc.

  6. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  7. Burden of a multiple sclerosis relapse: the patient's perspective.

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    Oleen-Burkey, Merrikay; Castelli-Haley, Jane; Lage, Maureen J; Johnson, Kenneth P

    2012-01-01

    Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the

  8. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple