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Sample records for active multiple sclerosis

  1. Evidence of platelet activation in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Alexander J Steven

    2008-06-01

    Full Text Available Abstract Objective A fatality in one multiple sclerosis (MS patient due to acute idiopathic thrombocytopenic purpura (ITP and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP, P-selectin expression (CD62p, circulating platelet microaggragtes (PAg], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.

  2. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  3. 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...

  4. Activation of Necroptosis in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dimitry Ofengeim

    2015-03-01

    Full Text Available Multiple sclerosis (MS, a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and Huntington’s disease (HD. Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS.

  5. Falls and Physical Activity in Persons with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    J. J. Sosnoff

    2012-01-01

    Full Text Available Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P.05. Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis.

  6. 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 wit

  7. 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…

  8. 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...

  9. 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...

  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; Multiple Sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P. [Universitaet des Saarlandes, Abteilung fuer Diagnostische und Interventionelle Neuroradiologie, Radiologische Klinik, Homburg/Saar (Germany); Shariat, K. [Universitaet des Saarlandes, Klinik fuer Neurochirurgie, Homburg/Saar (Germany); Kostopoulos, P. [Universitaet des Saarlandes, Klinik fuer Neurologie, Homburg/Saar (Germany)

    2008-06-15

    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.) [German] Die Multiple Sklerose (MS) ist die haeufigste chronisch-entzuendliche Erkrankung des Myelins mit eingesprengten Laesionen im Bereich der weissen Substanz des zentralen Nervensystems. Die Magnetresonanztomographie (MRT) hat bei der Diagnosestellung und Verlaufskontrolle eine Schluesselrolle. Dieser Artikel befasst sich mit Hauptcharakteristika der MR-Bildbebung. (orig.)

  13. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B

    2004-01-01

    We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal...... and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant i......NOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age...

  14. Activation of endogenous neural stem cells for multiple sclerosis therapy

    Directory of Open Access Journals (Sweden)

    Iliana eMichailidou

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability.A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs. Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

  15. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

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

  16. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

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

    2014-01-01

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

  17. National Multiple Sclerosis Society

    Science.gov (United States)

    ... Join the Community Stay Informed Corporate Support National Multiple Sclerosis Society Meet the Challenge to end MS Give ... in MS Research November 2, 2016 View All Multiple Sclerosis News & Press View All Clinical Trial Alerts Every ...

  18. Multiple sclerosis - discharge

    Science.gov (United States)

    ... Symptoms of Multiple Sclerosis . 6th ed. Philadelphia, PA: Springer Demos; 2014. Read More Multiple sclerosis Neurogenic bladder ... medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- ...

  19. Multiple Sclerosis in Children

    Directory of Open Access Journals (Sweden)

    Soroor INALOO

    2013-06-01

    , Altmann DR, Barkhof F, et al. MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study. Lancet Neurol 2007 Aug;6(8:677-86.33. Rovira A, Swanton J, Tintore M, Sastre-Garriga J, Horga A, et al. A single, early magnetic resonance imaging study in the diagnosis of multiple sclerosis. Arch Neurol 2009 May;66(5:587-92.34. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983 Mar;13(3:227-31.35. Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011 Feb; 69(2:292-302.36. Mikaeloff Y, Adamsbaum C. Husson B, Vallee L, Ponsot G, Confavreux C. et al. MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 2004 Sep;127(Pt9:1942-7.37. Chabas D, Castillo-Trivino T, Mowry EM, Strober JB, Glenn OA, Woubant E, et al. Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype? Neurology 2008 Sep;71(14:1090-3.38. Krupp LB, Banwell B, Tenembaum S. Consensus definitions proposed for pediatric multiple sclerosis andrelated disorder. Neurology 2007 Apr;68(16 Suppl 2:S7-S12.39. Yeh EA, Chitnis T, Krupp L, Ness J, Chabas D, Kuntz N, et al. Pediatric multiple sclerosis. Nat Rev Neurol 2009 Nov;5(11:621-31.40. Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardien M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007 Oct;6(10:887-902.41. Venkateswaran S, Banwell B. Pediatric multiple sclerosis. Neurologist 2010 Mar;16(2:92-105.42. Waubant E, Chabas D, Okuda DT, Glenn O, Mowry E, Henry RG, et al. Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol 2009 Aug; 66(8:967-71.43. Ghassemi R, Antel SB

  20. Activities-specific balance confidence in people with multiple sclerosis.

    Science.gov (United States)

    Nilsagård, Ylva; Carling, Anna; Forsberg, Anette

    2012-01-01

    Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1-6). Outcome Measures. Timed Up and Go, Timed Up and Go(cog), 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to -0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at α = 0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society.

  1. 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.

  2. Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study

    DEFF Research Database (Denmark)

    Oturai, A.B.; Koch-Henriksen, N.; Petersen, T.;

    2009-01-01

    INTRODUCTION: Previous studies of natalizumab (Tysabri) in relapsing multiple sclerosis (MS) patients have included patients with moderate disease activity. We studied a patient population with high disease activity. PATIENTS AND METHODS: We analyzed data from 234 consecutive, natalizumab-treated...

  3. Increased microglial catalase activity in multiple sclerosis grey matter.

    Science.gov (United States)

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  4. Suicide and multiple sclerosis

    DEFF Research Database (Denmark)

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

    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...

  5. Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

    Science.gov (United States)

    Motl, Robert W.; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S.

    2009-01-01

    Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

  6. Vision and multiple sclerosis.

    Science.gov (United States)

    Hickman, Simon J; Raoof, Naz; McLean, Rebecca J; Gottlob, Irene

    2014-01-01

    Multiple sclerosis can affect vision in many ways, including optic neuritis, chronic optic neuropathy, retrochiasmal visual field defects, higher order cortical processing, double vision, nystagmus and also by related ocular conditions such as uveitis. There are also side effects from recently introduced multiple sclerosis treatments that can affect vision. This review will discuss all these aspects and how they come together to cause visual symptoms. It will then focus on practical aspects of how to recognise when there is a vision problem in a multiple sclerosis patient and on what treatments are available to improve vision.

  7. Activities of daily living and lesion position among multiple sclerosis patients by Bayes network

    Institute of Scientific and Technical Information of China (English)

    Zhifang Pan; Hongtao Lu; Qi Cheng

    2013-01-01

    Magnetic resonance imaging is a highly sensitive approach for diagnosis of multiple sclerosis, and T2-weighted images can reveal lesions in the cerebral white matter, gray matter, and spinal cord. However, the lesions have a poor correlation with measurable clinical disability. In this study, we performed a large-scale epidemiological survey of 238 patients with multiple sclerosis in eleven districts by network member hospitals in Shanghai, China within 1 year. The involved patients were scanned for position and size of lesions by MRI. Results showed that lesions in the cerebrum, spinal cord, or supratentorial position had an impact on the activities of daily living in multiple sclerosis patients, as assessed by the Bayes network. On the other hand, brainstem lesions were very unlikely to influence the activities of daily living, and were not associated with the position of lesion, patient's gender, and patient's living place.

  8. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    Science.gov (United States)

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  9. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    Science.gov (United States)

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  10. Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

    Science.gov (United States)

    Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

    2013-01-01

    Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

  11. 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...... of their lives, emphasising the importance of rehabilitation in order to maintain quality of life. An important aspect of multiple sclerosis rehabilitation is the preservation of physical functioning. Hot topics in the rehabilitation of physical function include (1) exercise therapy, (2) robot-assisted training...... and (3) pharmacological interventions. Exercise therapy has for many years been a controversial issue in multiple sclerosis rehabilitation and the advice generally given to patients was not to participate in physical exercise, since it was thought to lead to a worsening of symptoms or fatigue. However...

  12. A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod

    DEFF Research Database (Denmark)

    Koch-Henriksen, Nils; Magyari, Melinda; Sellebjerg, Finn;

    2016-01-01

    BACKGROUND: Natalizumab and fingolimod were approved for treatment of active relapsing-remitting multiple sclerosis (RRMS) in Denmark in 2006 and 2011, respectively. There have been no randomized head-to-head studies comparing the two drugs. OBJECTIVE: To compare the clinical efficacy...... of natalizumab and fingolimod. METHODS: Data on all Danish RRMS patients who started their first second-line treatment with natalizumab or fingolimod from July 2011 to March 2015 were prospectively recorded in the Danish Multiple Sclerosis (MS) Treatment Register. The two treatment arms were 1:1 propensity score...

  13. Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Schaaf, M; Teelken, A

    1999-01-01

    The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter

  14. Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis

    NARCIS (Netherlands)

    F. Noorbakhsh (Farshid); K. Tsutsui (Kazuyoshi); N. Vergnolle (Nathalie); L.A. Boven (Leonie); S.F. Shariat (Shahrokh); M. Vodjgani (Mohammed); K.G. Warren (Kenneth); P. Andrade-Gordon (Patricia); N.K. Hollenberg (Norman); C. Power (Christopher)

    2006-01-01

    textabstractThe proteinase-activated receptors (PARs) are widely recognized for their modulatory properties of inflammation and neurodegeneration. We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in mice. PA

  15. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Science.gov (United States)

    Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

    2015-01-01

    Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  16. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Lucy Matthews

    Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  17. Multiple sclerosis: An overview

    Directory of Open Access Journals (Sweden)

    Ganesh N. Sharma

    2014-10-01

    Full Text Available The multiples sclerosis, involves the degeneration of neurones, leading to slowing in conduction of impulses as well as leading scars. A number of causative factors have been suggested for MS, yet the exact aetiology is unknown. The diagnosis as well as treatment methods including steroidal moieties are being used in common practice, yet a specific diagnosis procedure is required. Beside these the overcome from the adverse reactions of steroids are also required. Aim of present article is to summerise the various aspects of multiples sclerosis.

  18. 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 ...

  19. Tremor in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Mostert, Jop; Heersema, Dorothea; De Keyser, Jacques

    2007-01-01

    Tremor is estimated to occur in about 25 to 60 percent of patients with multiple sclerosis (MS). This symptom, which can be severely disabling and embarrassing for patients, is difficult to manage. Isoniazid in high doses, carbamazepine, propranolol and gluthetimide have been reported to provide som

  20. [Therapies in multiple sclerosis].

    Science.gov (United States)

    Kesselring, Jürg

    2013-08-21

    Although there is still no cure for Multiple Sclerosis (MS), effective strategies are available to modify the disease course, to treat relapses, to manage symptoms, to improve functions, and to provide emotional support. In combination, these treatments enhance the quality of life for people living with MS.

  1. Zinc in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Bredholt, Mikkel; Frederiksen, 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...

  2. 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 part

  3. Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup; Hedegaard, Chris Juul; Krakauer, M;

    2011-01-01

    Background: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent....... Objectives: We studied the immunological response to GA and its relationship with disease activity. Methods: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain...

  4. Immunopathogenesis of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Racke Michael

    2009-01-01

    Full Text Available Multiple sclerosis (MS is a suspected autoimmune disease in which myelin-specific CD4+ and CD8+ T cells enter the central nervous system (CNS and initiate an inflammatory response directed against myelin and other components of the CNS. Acute MS exacerbations are believed be the result of active inflammation, and progression of disability is generally believed to reflect accumulation of damage to the CNS, particularly axonal damage. Over the last several years, the pathophysiology of MS is being appreciated to be much more complex, and it appears that the development of the MS plaque involves a large number of cell populations, including CD8+ T lymphocytes, B cells, and Th17 cells (a population of helper T cells that secrete the inflammatory cytokine IL-17. The axonal transection and degeneration that is thought to represent the basis for progressive MS is now recognized to begin early in the disease process and to continue in the progressive forms of the disease. Molecules important for limiting aberrant neural connections in the CNS have been identified, which suppress axonal sprouting and regeneration of transected axons within the CNS. Pathways have also been identified that prevent remyelination of the MS lesion by oligodendrocyte precursors. Novel neuroimaging methodologies and potential biomarkers are being developed to monitor various aspects of the disease process in MS. As we identify the pathways responsible for the clinical phenomena of MS, we will be able to develop new therapeutic strategies for this disabling illness of young adults.

  5. Tuberous Sclerosis: Multiple Presentations

    Directory of Open Access Journals (Sweden)

    M. Sanei Taheri

    2008-01-01

    Full Text Available Introduction: Tuberous sclerosis is an autosomal do-minant genetic disorder that involves multiple or-gans. The predominant lesions are the hamartomas. Classically tuberous sclerosis has been characterized by a classic clinical triad of facial angiofibromas in 90%,retardation in 50-80%,seizure 80-90% and all three in 30%."nThe disease occurs in 1:100,000 persons in all races with nearly equal distribution between the sexes. "nCase Presentation: We had six patients who admitted with different presentations of tuberous sclerosis with a past history of convulsion from childhood, skin le-sions and mental retardation, also with new onset headache and changed pattern of convulsion. In physical examination facial angiofibromas and sub-ungual fibromas apparently detected. Brain CT scan study with contrast showed multiple calcified nod-ules associated with tubers and ventriculomegaly, also an enhancing enlarged nodule at foramen of mo-nro, which was suggestive of subependymal giant cell astrocytoma (SGCA. In abdominal and pelvic CT scan and ultrasonography, massive bilateral angio-myolipomatosis diagnosed. Also Focal hypodense le-sions in liver which were hyperechoic in ultrasono-graphy were diagnosed. With MRI study tubers, white matter lesions and subependymal nodules asso-ciated with SGCA were detected better. After surgery SGCA was proved."nDiscussion: Our patients had different presentations and various findings of this spectrum discussed in this lecture.

  6. Demyelination versus remyelination in progressive multiple sclerosis

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  7. 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...

  8. Multiple Sclerosis: An Update.

    Science.gov (United States)

    Faguy, Kathryn

    2016-05-01

    Multiple sclerosis (MS) is the most common disabling neurologic condition in young adults and imposes high financial and quality of life costs on patients, their families, and society. Yet, developments in the battle against MS include new treatments to slow its progression and updated diagnostic criteria that can accelerate diagnosis and effective treatment. This article offers a review and update on the disease, focusing on risk factors and possible causes, symptoms, forms of MS, diagnostic criteria and tools, and the expanding array of approved treatments. It also reports on the skyrocketing cost of MS drugs, misdiagnosis, and special patient populations with MS.

  9. Subcutaneous administration of alemtuzumab in patients with highly active multiple sclerosis.

    Science.gov (United States)

    Perumal, Jai S; Foo, Farng; Cook, Perry; Khan, Omar

    2012-08-01

    Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic lymphoid leukemia as IV. Oncology guidelines recommend alemtuzumab subcutaneous (SC) over IV. There is no report of alemtuzumab SC in MS. We report two patients with highly active relapsing MS who were treated with SC alemtuzumab, had significant improvement and tolerated SC alemtuzumab well without the typical infusion-associated adverse events. SC alemtuzumab in MS warrants further studies as this may enhance patient convenience and minimize infusion-associated adverse events.

  10. Exercise May Not Lower Women's Risk of Multiple Sclerosis

    Science.gov (United States)

    ... html Exercise May Not Lower Women's Risk of Multiple Sclerosis Study shows no benefit, but staying active can ... suggests they won't lower the risk of multiple sclerosis (MS). The new study "did not provide evidence ...

  11. Intractable and highly active relapsing multiple sclerosis – role of alemtuzumab

    Directory of Open Access Journals (Sweden)

    Dubey D

    2015-09-01

    Full Text Available Divyanshu Dubey,1 Christopher A Cano,1 Olaf Stuve1–3 1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 2Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA; 3Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Abstract: Alemtuzumab is a humanized recombinant monoclonal antibody that was recently approved by the US Food and Drug Administration and the European Medicines Agency for the management of relapsing forms of multiple sclerosis (MS. It has been utilized for the management of chronic lymphocytic leukemia, bone marrow and renal transplantation, or graft versus host disease. Because of its immunomodulatory properties, it was brought into clinical development in MS. One Phase II (CAMMS223 and two Phase III clinical trials (CARE-MSI and -II have evaluated the safety and efficacy of alemtuzumab in patients with relapsing–remitting MS. Even though its efficacy profile and long-lasting effect have attracted much interest among physicians and patients, it has significant potential adverse effects that may limit its use to patients with active disease. Here, we review the history of drug development of alemtuzumab. Furthermore, we outline the postulated mechanisms of action, clinical evidence, and safety of alemtuzumab for its use as a disease-modifying agent in active and highly active MS. Keywords: alemtuzumab, multiple sclerosis, monoclonal antibody, CD52, idiopathic thrombocytopenic purpura

  12. Demyelination versus remyelination in progressive multiple sclerosis.

    Science.gov (United States)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans; Koch-Henriksen, Nils; Lucchinetti, Claudia F; Sørensen, Per S; Laursen, Henning

    2010-10-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments for other plaque types and plaque number (Pprogressive multiple sclerosis. By contrast, there were no group differences in the brain load or frequency of low-grade inflammatory plaques with slowly expanding demyelination. Spinal cord lesion loads and remyelination capacity were also comparable in the two patient groups. Remyelinated areas were more vulnerable than the normal-appearing white matter to new demyelination, including active demyelination in secondary progressive multiple sclerosis. 'Recurrent' slowly expanding demyelination, affecting remyelinated areas, and the load of slowly expanding demyelination correlated with incomplete remyelination in both groups. In turn, incomplete remyelination in the spinal cord correlated with higher disease-related disability (determined retrospectively; r = -0.53; Pprogressive multiple sclerosis. These patients may, thereby, be spared symptoms until the spinal cord is affected. By contrast, recurrent active demyelination of repaired myelin could explain why similar symptoms often develop in consecutive relapses in relapsing

  13. Effects of physical activity on functional and cardio respiratory capacity in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Corina Pantea

    2011-12-01

    Full Text Available Multiple sclerosis (MS is an inflammatory, demyelinising disease of the central nervous system which accounts for functional impairment and lasting disability in young adults. It occurs as a result of some combination of genetic susceptibility, deregulation of the immune system and environmental factors such as infectious and possibly other factors like vascular problems. The objective of this paper is to demonstrate if an intensive short-term inpatient rehabilitation program is able to improve clinical and functional outcome in multiple sclerosis patients. Methods: 15 patients with multiple sclerosis (mean age 37.06±9.66 years were assigned to Expanded Disability Status Scale (EDSS score. All patients were included in an intensive short-term rehabilitation program (strength and cardio respiratory exercises. Subjects attended 60-min sessions three times a week for 12 weeks. Ruffier-Dickson and Hettinger tests were performed. The patients were assessed before and after this physical intervention. Results: From the total 25 patients 50% were with remitting multiple sclerosis, 30% with secondary progressive multiple sclerosis and 20% with primary progressive multiple sclerosis. The EDSS score was improved in 70% of studied cases. All subjects recorded a better cardio respiratory performance evaluated by Ruffier-Dickson test. Hettinger assessment recorded after 12 weeks an improvement of 80% in the functional state. Conclusions: Strength (or resistance training and cardio respiratory (or endurance training are two basic physical exercises widely used in neurological rehabilitation. Application of an intensive rehabilitation program determines increasing of functional and cardio respiratory capacity in patients with multiple sclerosis.

  14. 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.

  15. Attributions and self-efficacy for physical activity in multiple sclerosis.

    Science.gov (United States)

    Nickel, D; Spink, K; Andersen, M; Knox, K

    2014-01-01

    Self-efficacy is an important predictor of health-related physical activity in multiple sclerosis (MS). While past experiences are believed to influence efficacy beliefs, the explanations individuals provide for these experiences also may be critical. Our objective was to test the hypothesis that perceived success or failure to accumulate 150 min of physical activity in the previous week would moderate the relationship between the attributional dimension of stability and self-efficacy to exercise in the future. Forty-two adults with MS participated in this cross-sectional descriptive study. Participants completed questions assessing physical activity, perceived outcome for meeting the recommended level of endurance activity, attributions for the outcome, and exercise self-efficacy. Results from hierarchical multiple regression revealed a significant main effect for perceived outcome predicting self-efficacy that was qualified by a significant interaction. The final model, which included perceived outcome, stability, and the interaction term, predicted 37% of the variance in exercise self-efficacy, F (3, 38) = 7.27, p = .001. Our findings suggest that the best prediction of self-efficacy in the MS population may include the interaction of specific attributional dimensions with success/failure at meeting the recommended physical activity dose. Attributions may be another target for interventions aimed at increasing the physical activity in MS.

  16. 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....

  17. 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...

  18. Statin treatment in multiple sclerosis

    DEFF Research Database (Denmark)

    Pihl-Jensen, Gorm; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2015-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that leads to progressive disability. Statins [hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors] are widely prescribed drugs in hypercholesterolemia. They exert immunomodulatory and neurotrophic effects and are attractive...

  19. A Formative Evaluation of Customized Pamphlets to Promote Physical Activity and Symptom Self-Management in Women with Multiple Sclerosis

    Science.gov (United States)

    Plow, Matthew; Bethoux, Francois; Mai, Kimloan; Marcus, Bess

    2014-01-01

    Inactivity is a prevalent problem in the population affected with multiple sclerosis (MS). Thus, there is a need to develop and test physical activity (PA) interventions that can be widely disseminated. We conducted a formative evaluation as part of a randomized controlled trial of a pamphlet-based PA intervention among 30 women with MS. Pamphlets…

  20. Therapeutics for multiple sclerosis symptoms.

    Science.gov (United States)

    Ben-Zacharia, Aliza Bitton

    2011-01-01

    Symptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less-common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope.

  1. Multiple sclerosis and behavior.

    Science.gov (United States)

    Pinkston, James B; Kablinger, Anita; Alekseeva, Nadejda

    2007-01-01

    Multiple sclerosis (MS) is one of the most frequently seen neurological causes of progressive disability in early to middle adulthood. The disease is variable in its presentation and course, affects roughly 100-300 per 100,000 persons within the United States alone, and is slightly more common among females than males. MS places substantial burdens on patients, families, and caregivers. It negatively affects cognitive abilities and psychiatric functioning, and can add a notably deleterious effect on a patient's quality of life. This chapter reviews the recent literature on the behavioral manifestations of MS. Cognitive domains discussed include executive functioning, processing speed, attention, learning and memory, language functioning, and visual spatial processing. Some attention will also be paid to differential diagnosis and the cognitive effects of treatment. Psychiatric manifestations are also discussed, including symptoms of depression, bipolar disorder, euphoria, pathological laughter and crying, and psychosis, as well as maladaptive personality traits. Finally, the chapter concludes with a discussion of the effects of MS on quality of life including such areas as fatigue, sexual dysfunction, pain, employment, and cognitive functioning.

  2. Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Blankenhorn Elizabeth P

    2006-09-01

    Full Text Available Abstract Background There is increased interest in the contribution of the innate immune system to multiple sclerosis (MS, including the activity of acute inflammatory mediators. The purpose of this study was to test the involvement of systemic secreted phospholipase A2 (sPLA2 enzymes in experimental autoimmune encephalomyelitis (EAE, an MS model, and to determine if enzyme activity is elevated in MS patients. Methods A non-invasive urinary assay was developed in order to monitor enzymatically active sPLA2 levels in Dark Agouti rats after induction of EAE. Some Rats were treated with nonapeptide CHEC-9, an uncompetitive sPLA2 enzyme inhibitor, during the initial rise in urinary enzyme levels. Body weight and clinical EAE score were measured for 18 days post immunization (PI, after which the rats were sacrificed for H&E and myelin staining, and for ED-1 immunocytochemistry, the latter to quantify macrophages and activated microglia. The urinary sPLA2 assay was also applied to un-timed samples collected from a cross section of 44 MS patients and 14 healthy controls. Results Mean levels of enzymatically active sPLA2 in the urine increased following immunization and peaked between days 8–10 PI which was just prior to the onset of EAE symptoms. At this time, a transient attenuation of activity was detected in the urine of CHEC-9 treated rats consistent with the activity-dependent properties of the inhibitor. The peptide also reduced or abolished EAE symptoms compared to vehicle-injected controls. Histopathological changes in the spinal cords of the EAE rats correlated generally with clinical score including a significant reduction in ED-1+ cells after peptide treatment. Multiple Sclerosis patients also showed elevations in sPLA2 enzyme activity. Mean levels of sPLA2 were increased 6-fold in the urine of patients with active disease and 4-fold for patients in remission, regardless of immunomodulating therapy. Conclusion The results suggest that s

  3. Effectiveness of rehabilitation in multiple sclerosis relapse on fatigue, self-efficacy and physical activity.

    Science.gov (United States)

    Nedeljkovic, Una; Raspopovic, Emilija Dubljanin; Ilic, Nela; Vujadinovic, Sanja Tomanovic; Soldatovic, Ivan; Drulovic, Jelena

    2016-09-01

    Relapse of disease is one of the most prominent characteristics of multiple sclerosis. Effectiveness of rehabilitation programmes on fatigue, self-efficacy (SE) and physical activity (PA) has not been investigated so far in context of relapse. The aim of our study was to examine if rehabilitation programme in addition to high-dose methylprednisolone (HDMP) during relapse of disease can influence fatigue, SE and PA more than corticosteroid therapy alone. Patients were randomized in control group receiving only HDMP and experimental group which was in addition included in rehabilitation programme. Outcome measures used were Fatigue Severity Scale (FSS), Multiple Sclerosis Self- Efficacy scale (MSSES), Godin Leisure-Time Exercise Questionnaire (GLTEQ), completed on baseline, 1 and 3 months later. There was no significant change in FSS in both time points, despite different trend seen between groups. The mean MSSES for function and control improved significantly in treatment group after 1 month (807.1 ± 96.8, p = 0.005; 665.3 ± 145.1, p = 0.05) and 3 months (820 ± 83.5, p = 0.004; 720.0 ± 198.2, p = 0.016.) compared to baseline values. The mean GLTEQ score was significantly higher in the treatment group compared to the control at both follow-up time points (45.7 ± 7.6, p < 0.001; 34.3 ± 22.4, p < 0.01). Rehabilitation started along with corticosteroid treatment induced significant improvement in PA compared to HDMP therapy alone. It also influenced noticeable changes in self-efficacy, but effect on fatigue was insufficient.

  4. Matrix Metalloproteinases in patients with Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Rebeca A. Fernández Carriera

    2007-05-01

    Full Text Available Fundament: The proteolitic rupture of the extracellular matrix due to metalloproteinase 2 and 9 is one of the aspects that can influence in the alteration of the permeability of the blood-brain barrier (BBB in multiple sclerosis. Objective: To determine metalloproteinase activity with gelatinous activity in patients suffering from multiple sclerosis. Methods: the cerebrospinal fluid (CSF samples taken from 31 patients suffering from multiple sclerosis and a control group formed by 21 patients without neurological disease. The metalloproteinase 2 and 9 activities in the cerebrospinal fluid were determined by zimográfica technique through polyacrylamide gel electrophoresis. The bands were later analysed by their molecular weight and the relative metalloproteinase 9 activity was calculated. Total protein concentrations, albumin and immunoglobulin G (IgG, the IgG rate and the Q rate were assessed to evaluate the IgG intrathecal and the functional state of the blood-brain barrier. Results: metalloproteinase 2 activity was detected in the cerebrospinal fluid of all patients and control group. Metalloproteinase 9 activity was only found in the 61.3 % of the patients. The presence of relative metalloproteinase 9 activity was neither associated with the clinical variables nor the laboratory ones. An association was found between its presence and the oligoclonal bands in patients with multiple sclerosis. In those patients under immunomodular treatment it was presented with less frequency. Conclusions: There is a possible participation of Metalloproteinase 9 in the immunopathological mechanisms of the multiple sclerosis.

  5. Indoleamine 2,3 Dioxygenase (IDO Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Roberta Mancuso

    Full Text Available Interferon gamma (IFN-γ production induces the transcription of indoleamine 2,3 dioxygenase (IDO resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS patients.IDO and interferon-γ (IFN-γ gene expression, serum IDO activity (Kynurenine/Tryptophan ratio and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS and 15 healthy controls (HC. PBMCs samples in AMS patients were collected before (BT-AMS and during glucocorticoids-based therapy (DT-AMS.IDO expression was increased and IFN-γ was decreased (p<0.001 in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001. Serum neopterin concentration followed the same trend as IDO expression and activity.Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS.

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

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe;

    2012-01-01

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

  7. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...

  8. Top 10 Research Questions Related to Physical Activity and Multiple Sclerosis

    Science.gov (United States)

    Motl, Robert W.; Learmonth, Yvonne C.; Pilutti, Lara A.; Gappmaier, Eduard; Coote, Susan

    2015-01-01

    An estimated 2.5 million people worldwide are living with multiple sclerosis (MS), and this disease may be increasing in prevalence. MS is a disease of the central nervous system that is associated with heterogeneous symptoms and functional consequences, and the current first-line disease-modifying therapies often become ineffective later in the…

  9. Sudden cardiac death in multiple sclerosis caused by active demyelination of the medulla oblongata

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Kusters, B.

    2011-01-01

    Cardiovascular autonomic dysfunction is not uncommon in multiple sclerosis (MS) and is related to the involvement of the vegetative areas of cardiac innervations in the medulla oblongata. It has been suggested that this may contribute to the occurrence of sudden death in MS. In this case report, we

  10. Outcome expectations and physical activity in persons with longstanding multiple sclerosis.

    Science.gov (United States)

    Morrison, Janet D; Stuifbergen, Alexa K

    2014-06-01

    Research suggests that persons with multiple sclerosis (MS) are much less physically active than the general population and that increased physical activity in persons with MS is associated with numerous benefits such as improvements in fatigue, mobility, and quality of life (). Potentially modifiable theory-based determinants of physical activity behavior need to be identified so that researchers may study their effectiveness in randomized clinical trials and clinicians may integrate them into practice to promote physical activity in this population. The purpose of this study was to explore the multidimensional (physical, social, and self-evaluative) outcome expectations for physical activity among persons with longstanding MS. A sample of 369 participants diagnosed with MS for more than 15 years completed surveys to measure multidimensional outcome expectations for exercise, MS functional limitations, and physical activity using two different instruments: one measuring physical activity engagement and the other measuring physical activity capability. Results indicated that MS functional limitation was the strongest predictor of both physical activity engagement and physical activity capability. Physical and social outcome expectations contributed to the model explaining 12% of the variation in physical activity engagement, whereas none of the outcome expectancy dimensions (physical, social, or self-evaluative) contributed to the model explaining variation in physical activity capability. Although analyses of cross-sectional data do not infer causation, these findings suggest that positive physical and social outcome expectations for physical activity are associated with engagement in physical activity as well as being potential sources of motivation for increasing physical activity behavior in individuals living with longstanding MS.

  11. Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis.

    Science.gov (United States)

    Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

    2016-02-18

    Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression.

  12. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Directory of Open Access Journals (Sweden)

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  13. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

    Science.gov (United States)

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-07-02

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

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

    Directory of Open Access Journals (Sweden)

    Finn Sellebjerg

    Full Text Available Although treatment of multiple sclerosis (MS with the type I interferon (IFN IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4 on CD4+CD26(high T cells (Th1 helper cells, and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high T cells, and the percentage of CD4+CD26(high T cells that were CD49d(high correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells, and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

  15. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis.

    Science.gov (United States)

    Thell, Kathrin; Hellinger, Roland; Sahin, Emine; Michenthaler, Paul; Gold-Binder, Markus; Haider, Thomas; Kuttke, Mario; Liutkevičiūtė, Zita; Göransson, Ulf; Gründemann, Carsten; Schabbauer, Gernot; Gruber, Christian W

    2016-04-12

    Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders.

  16. Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis.

    Science.gov (United States)

    Howell, Owain W; Rundle, Jon L; Garg, Anurag; Komada, Masayuki; Brophy, Peter J; Reynolds, Richard

    2010-10-01

    The complex manifestations of chronic multiple sclerosis (MS)are due in part to widespread axonal abnormalities that affect lesional and nonlesional areas in the central nervous system. We describe an association between microglial activation and axon/oligodendrocyte pathology at nodal and paranodal domains in normal-appearing white matter (NAWM) of MS cases and in experimental autoimmune encephalomyelitis (EAE). The extent of paranodal axoglial (neurofascin-155(+)/Caspr1(+)) disruption correlated with local microglial inflammation and axonal injury (expression of nonphosphorylated neurofilaments) in MS NAWM. These changes were independent of demyelinating lesions and did not correlate with the density of infiltrating lymphocytes. Similar axoglial alterations were seen in the subcortical white matter of Parkinson disease cases and in preclinical EAE, at a time point when there is microglial activation before the infiltration of immune cells. Disruption of the axoglial unit in adjuvant-immunized animals was reversible and coincided with the resolution of microglial inflammation; paranodal damage and microglial inflammation persisted in chronic EAE. Axoglial integrity could be preserved by the administration of minocycline, which inhibited microglial activation, in actively immunized animals. These data indicate that, in MS NAWM, permanent disruption to axoglial domains in an environment of microglial inflammation is an early indicator of axonal injury that likely affects nerve conduction and may contribute to physiologic dysfunction.

  17. Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Rachel E. Klaren

    2015-01-01

    Full Text Available Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS. Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV, normalized WM volume (NWMV, and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA was significantly associated with NGMV (pr=0.370, p<0.05, NWMV (pr=0.433, p<0.01, hippocampus (pr=0.499, p<0.01, thalamus (pr=0.380, p<0.05, caudate (pr=0.539, p<0.01, putamen (pr=0.369, p<0.05, and pallidum (pr=0.498, p<0.01 volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.

  18. Evidence of impaired brain activity balance after passive sensorimotor stimulation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Nikolaos Petsas

    Full Text Available OBJECTIVES: Examination of sensorimotor activation alone in multiple sclerosis (MS patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation. Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. METHODS: 13 relapsing remitting-MS patients (RRMS, 18 secondary progressive-MS patients (SPMS and 15 healthy controls (HC underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV from both T1- and T2-weighted images. RESULTS: Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HCactivation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV. CONCLUSION: In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher

  19. Activation of Blood CD3+CD56+CD8+ T Cells during Pregnancy and Multiple Sclerosis

    Science.gov (United States)

    de Andrés, Clara; Fernández-Paredes, Lidia; Tejera-Alhambra, Marta; Alonso, Bárbara; Ramos-Medina, Rocío; Sánchez-Ramón, Silvia

    2017-01-01

    A striking common feature of most autoimmune diseases is their female predominance, with at least twice as common among women than men in relapsing–remitting multiple sclerosis (MS), the prevailing MS clinical form with onset at childbearing age. This fact, together with the protective effect on disease activity during pregnancy, when there are many biological changes including high levels of estrogens and progesterone, puts sex hormones under the spotlight. The role of natural killer (NK) and NKT cells in MS disease beginning and course is still to be elucidated. The uterine NK (uNK) cells are the most predominant immune population in early pregnancy, and the number and function of uNK cells infiltrating the endometrium are sex-hormones’ dependent. However, there is controversy on the role of estrogen or progesterone on circulating NK (CD56dim and CD56bright) and NKT cells’ subsets. Here, we show a significantly increased activation of CD3+CD56+CD8+ cells in pregnant MS women (MSP) compared with non-pregnant MS women (NPMS) (p pregnancy. Further studies on specific CD8+ NKT cells function and their role in pregnancy beneficial effects on MS are warranted to move forward more effective MS treatments. PMID:28280497

  20. Cognitive deficits in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2012-01-01

    Objectives - Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part...... Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. Results - We found distinct...

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

    Directory of Open Access Journals (Sweden)

    Kurt-Wolfram Sühs

    2016-09-01

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

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

    Science.gov (United States)

    Sühs, Kurt-Wolfram; Papanagiotou, Panagiotis; Hein, Katharina; Pul, Refik; Scholz, Kerstin; Heesen, Christoph; Diem, Ricarda

    2016-01-01

    Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV) daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS) based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group. PMID:27706045

  3. Accelerated Cure Project for Multiple Sclerosis

    Science.gov (United States)

    ... main content Accelerating research toward a cure for multiple sclerosis Home Contact Us Search form Search Connect Volunteer ... is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

  4. Emotional Disorders in People with Multiple Sclerosis

    Science.gov (United States)

    ... 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 main findings of a ...

  5. The impact of mitoxantrone on neurological disability in active multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Mesaroš Šarlota

    2004-01-01

    Full Text Available Several in vivo and in vitro studies showed that mitoxantrone (MTX, a novel anthracendione antineoplastic agent, had an immunomodulatory effect that suppressed humoral immunity, reduced T-cell numbers, lessened helper activity, enhanced suppressor function and had some positive effect on acute and chronic experimental allergic encephalomyelitis in rats. Up to now, several trials of therapy with MTX have been performed in patients with multiple sclerosis (MS. MTX has been recently shown to reduce disease activity, as expressed by reducing relapse rate and decreasing new, active MRI lesions, in a selected group of patients with active relapsing-remitting (RR MS. Furthermore, more recently, it has been demonstrated that MTX reduce neurological disability in secondary progressive MS. We designed the open-label clinical trial involving 35 MS patients with active disease in order to evaluate the long-term clinical effects of 6-months MTX treatment during a follow-up period of 20-46 months (mean, 30 months. The study comprised 35 patients, who met the Poser criteria for clinically definite MS. All patients were clinically treated at the Institute of Neurology, Clinical Centre of Serbia, Belgrade, during the period from March 1996 to August 2000. The neurological disability state was evaluated at the entry, every month until completion of the therapy and every six months until August 2000, by means of Kurtzke Expanded Disability Status Scale (EDSS score. All patients had active MS. The criteria for disease activity were: 1 at least 2 relapses within the previous 2 years, or 2 progression of at least 1.0 point on EDSS scale during the same period. The included patients did not receive immunosuppressive therapy six months prior to the entry. The patients were assigned to receive MTX 20 mg intravenously (iv per month and methylprednisolone 1g iv per month, over six months. The clinical characteristics and demographic data of patients included in the study

  6. Anti-integrin therapy for multiple sclerosis.

    Science.gov (United States)

    Kawamoto, Eiji; Nakahashi, Susumu; Okamoto, Takayuki; Imai, Hiroshi; Shimaoka, Motomu

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  7. Anti-Integrin Therapy for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Eiji Kawamoto

    2012-01-01

    Full Text Available Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.

  8. Alemtuzumab treatment of multiple sclerosis.

    Science.gov (United States)

    Coles, Alasdair J

    2013-02-01

    Alemtuzumab is a humanized monoclonal antibody directed against CD52. A single cycle of alemtuzumab, administered over 5 days, depletes lymphocytes. Reconstitution causes prolonged alterations in the lymphocyte repertoire, with relatively increased regulatory T-cell numbers and reduced naïve T cells. It is currently approved for the treatment of B-cell chronic lymphocytic leukemia and is being considered for licensing for multiple sclerosis (MS).When first used, alemtuzumab successfully reduced relapses and new lesion formation based on magnetic resonance imaging in people with progressive MS, but this cohort continued to accumulate disability, associated with progressive cerebral atrophy, presumably due to axonal degeneration. From this experience, we advocated that immunotherapies should be given early in the course of the disease. Since then, one phase II and two phase III trials have shown that alemtuzumab reduces the relapse rate, compared with the active comparator interferon beta-1a (IFNβ-1a), in treatment-naïve and treatment-experienced MS up to 10 years from disease onset. Furthermore, in two of these trials, alemtuzumab reduced the risk of accumulating disability compared with IFNβ-1a; indeed alemtuzumab treatment led to an improvement in disability and reduction in cerebral atrophy. Safety issues are infusion-associated reactions, mainly controlled by methyl-prednisolone, antihistamines, and antipyretics; mild to moderate infections; and autoimmunity. After 5 years, 30 to 40% of alemtuzumab patients have developed autoimmunity, largely against the thyroid gland, but rarely (2%) against platelets in immune thrombocytopenia, and in a few cases, Goodpasture's renal syndrome.Alemtuzumab is an effective therapy for early relapsing-remitting multiple sclerosis, offering disability improvement at least to 5 years after treatment. Its use requires careful monitoring so that potentially serious side effects can be treated early and effectively.

  9. Social consequences of multiple sclerosis

    DEFF Research Database (Denmark)

    Pfleger, C C H; Flachs, E M; Koch-Henriksen, N

    2010-01-01

    BACKGROUND: Time to disability pension is one of the endpoints to be used to determine the prognosis of multiple sclerosis (MS) in prospective studies. OBJECTIVE:   To assess the time to cessation of work and receiving disability pension in MS, and how it may depend on gender, type of work and age...

  10. Vascular aspects of multiple sclerosis

    NARCIS (Netherlands)

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

    2011-01-01

    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 dy

  11. Genetics Home Reference: multiple sclerosis

    Science.gov (United States)

    ... or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms ...

  12. 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...

  13. 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...

  14. 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...

  15. Suicide attempts in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Elsebeth Nylev; Jensen, Børge; Stenager, Maria

    2011-01-01

    The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating...

  16. Defining secondary progressive multiple sclerosis.

    Science.gov (United States)

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  17. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  18. Hypovitaminosis D association with disease activity in relapsing remitting multiple sclerosis in Brazil.

    Science.gov (United States)

    Becker, Jefferson; Callegaro, Dagoberto; Lana-Peixoto, Marco Aurélio; Talim, Natália; Vidaletti, Tamara; de Paula Corrêa, Marcelo; Gomes, Irenio

    2016-04-15

    Multiple sclerosis (MS) onset is believed to result from a combination of environmental and genetic factors. A prevailing theory addresses the influence of hypovitaminosis D in the development of MS. This research aimed to study the association between vitamin D serum levels and MS, as a prognostic and risk factor for the development and progression of the disease. A cross-sectional multicenter study was conducted in patients with relapsing-remitting MS (n=67), according to the revised McDonald criteria (2010), accompanied in three MS centers in different Brazilian states. A control group consisted of healthy volunteers (n=61). Blood collections were carried out in late summer and late winter. This seems to be the first study of this kind in Latin America. The vitamin D serum levels for MS patients (29.63±8.08) in summer were similar to the controls (29.71±8.28); however, in winter they were lower than the healthy individuals (24.05±7.47 vs 26.56±8.01). No significant difference between the three cities was observed. No association was noted between vitamin D serum levels and gender, race and age, nor correlation of these levels with the EDSS or disease duration. In contrast, a significant association was seen between deficient vitamin D serum levels in late winter with disease activity, characterized by the onset of relapses (19.73±5.69 vs 25.30±6.22) or Gd+ lesions (17.22±3.11 vs 22.79±7.22).

  19. 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.

  20. 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 ...

  1. Autonomic disorders in multiple sclerosis.

    Science.gov (United States)

    Lensch, E; Jost, W H

    2011-01-01

    Multiple sclerosis is an inflammatory disease leading to disseminated lesions of the central nervous system resulting in both somatomotor and autonomic disturbances. These involve the central centers of the autonomic nervous system, as well as the automatic control and pathway systems. All autonomic functions may be disordered individually or in combined form. There is no other disease with a clinical picture so multifaceted. Besides cardiovascular dysfunctions disorders of bladder and rectum have become apparent. Somatomotor and autonomic disturbances occur with similar frequency; however the focused exam often heavily favors somatomotor symptoms. Autonomic disturbances should primarily be taken into account on history taking and clinical examination. Individual diagnosis and treatment is a secondary feature. Impairments of the autonomic nervous systems in multiple sclerosis are frequently overlooked.

  2. Autonomic Disorders in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    E. Lensch

    2011-01-01

    Full Text Available Multiple sclerosis is an inflammatory disease leading to disseminated lesions of the central nervous system resulting in both somatomotor and autonomic disturbances. These involve the central centers of the autonomic nervous system, as well as the automatic control and pathway systems. All autonomic functions may be disordered individually or in combined form. There is no other disease with a clinical picture so multifaceted. Besides cardiovascular dysfunctions disorders of bladder and rectum have become apparent. Somatomotor and autonomic disturbances occur with similar frequency; however the focused exam often heavily favors somatomotor symptoms. Autonomic disturbances should primarily be taken into account on history taking and clinical examination. Individual diagnosis and treatment is a secondary feature. Impairments of the autonomic nervous systems in multiple sclerosis are frequently overlooked.

  3. Multiple sclerosis - New treatment modalities

    Directory of Open Access Journals (Sweden)

    Rocco Totaro

    2015-01-01

    Full Text Available Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference.

  4. Molecular mimicry and multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Michael Namaka; Michael R. Mulvey; Sabina Kapoor; Leann Simms; Christine Leong; Amy Grossberndt; Michael Prouta; Emma Frost; Farid Esfahani; Andrew Gomori

    2011-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Although the exact underlying mechanism leading to myelin destruction is unknown, the molecular mimicry theory is the most commonly acknowledged elucidation of MS pathology. Although various antigens have been associated with MS induction, this review presents studies focused on key bacterial and viral antigens that lead to the development of MS. The research specific to a molecular mimicry theory of MS via each implicated agent is weak; however, collectively the reports provide credible support for this theory. Given that homologous sequences are not required to lead to antigenic cross-reactivity, it is reasonable to conclude that certain viral and bacterial antigens with 5-10 similar amino acids in sequence can lead to self destruction of similar myelin sequences. Thus, this literature review has provided insight to further the understanding of the etiology of multiple sclerosis.

  5. Epigenetic Drugs for Multiple Sclerosis

    OpenAIRE

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses ...

  6. Magnetic resonance in Multiple Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Scotti, G.; Scialfa, G.; Biondi, A.; Landoni, L.; Caputo, D.; Cazzullo, C.L.

    1986-07-01

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

  7. Rehabilitation challenges in multiple sclerosis.

    Science.gov (United States)

    Burks, Jack S; Bigley, George Kim; Hill, Harry Haydon

    2009-10-01

    While current immunomodulating drugs aim to reduce multiple sclerosis (MS) exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL) such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an 'extra' service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers.

  8. Rehabilitation challenges in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Burks Jack

    2009-01-01

    Full Text Available While current immunomodulating drugs aim to reduce multiple sclerosis (MS exacerbations and slow disease progression, rehabilitation aims to improve and maintain the functional abilities of patients in the face of disease progression. An increasing number of journal articles are describing the value of the many rehabilitation interventions that can be used throughout the course of the disease, from the initial symptoms to the advanced stages. An integrated team of healthcare professionals is necessary to address a myriad of problems to reduce impairments, disabilities, and handicaps. The problems may be related to fatigue, weakness, spasticity, mobility, balance, pain, cognition, mood, relationships, bowel, bladder, sexual function, swallowing, speech, transportation, employment, recreation, and activities of daily living (ADL such as dressing, eating, bathing, and household chores. The team can help prevent complications and secondary disabilities, while increasing patient safety. Improving neurologically related function, maintaining good relationships, and feeling productive and creative adds enormously to the quality of life of people with MS and their families. Rehabilitation is more than an ′extra′ service that is given after medical therapies; it is an integral part of the management of the diverse set of problems encountered throughout the course of the disease. An interdisciplinary team may have many members, including physicians, nurses, physical therapists, occupational therapists, speech and language pathologists, psychotherapists, social workers, recreational therapists, vocational rehabilitation therapists, patients, families, and other caregivers.

  9. 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.

  10. The Danish Multiple Sclerosis Treatment Register

    Directory of Open Access Journals (Sweden)

    Magyari M

    2016-10-01

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

  11. Evoked potentials in multiple sclerosis.

    Science.gov (United States)

    Kraft, George H

    2013-11-01

    Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs.

  12. [Multiple sclerosis: current therapies and future perspectives].

    Science.gov (United States)

    Matsushita, Takuya

    2011-11-01

    Multiple sclerosis is characterized by temporal and spatial dissemination of demyelination in the central nervous system. After a discovery of disease modifying effects of interferon beta and glatiramer acetate for multiple sclerosis, many drugs for disease modifying therapy have been developed. Recently, some multicenter studies have shown that early introduction of interferon beta or glatiramer acetate into patients with clinically isolated syndrome delayed the conversion to clinically definite multiple sclerosis. Newly developed disease modifying therapies for multiple sclerosis have a specific molecular target changing an immunological reaction and many of them are oral preparations instead of injectable first line therapies. Treatment options for multiple sclerosis are increasing and it is essential for the optimal treatment choice to collect information of the long-term side effects and the combined effects with first line therapies and to acquire the knowledge of the pathomechanisms about multiple sclerosis.

  13. The Danish Multiple Sclerosis Treatment Register

    OpenAIRE

    Magyari M; Koch-Henriksen N; Sørensen PS

    2016-01-01

    Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR) serves as a clinical quality register, e...

  14. [Diet and multiple sclerosis].

    Science.gov (United States)

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2014-05-16

    Introduccion. El tipo de dieta se ha relacionado con el proceso inflamatorio que forma parte de la esclerosis multiple (EM). En los ultimos años, distintas lineas de investigacion han generado una gran cantidad de conocimiento sobre la participacion de la dieta en la patogenesis de la EM. Objetivo. Elucidar de modo critico las evidencias que relacionan distintos tipos de dietas y alimentos con la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado el papel de la dieta en la patogenesis y en el tratamiento de la EM. Para explorar la asociacion entre la dieta y el riesgo de EM se ha revisado la evidencia disponible hasta el momento, pasando por estudios observacionales hasta terminar con estudios de intervencion. Conclusiones. Se necesita mas investigacion sobre la nutricion como factor de riesgo, ya que podria tener relacion con la enfermedad, y el control de esta podria llevar a una disminucion significativa de la incidencia o progresion de la patologia.

  15. [Smoking and multiple sclerosis].

    Science.gov (United States)

    Arruti, Maialen; Castillo-Triviño, Tamara; Egüés, Nerea; Olascoaga, Javier

    2015-02-16

    Introduccion. La esclerosis multiple (EM) es una enfermedad autoinmune de etiologia compleja, hoy por hoy desconocida, en la que factores geneticos y ambientales determinan la susceptibilidad. En los ultimos años, el efecto del tabaco ha sido uno de los factores ambientales que ha emergido en la EM, y se ha asociado tanto a un aumento de la susceptibilidad como a un aumento de la progresion. Objetivo. Revisar la evidencia actual sobre el papel del tabaco en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados que han analizado distintos aspectos del tabaco en la EM: vias patogenicas implicadas, asociacion del tabaco y riesgo de EM, interaccion con otros factores de riesgo y efecto del tabaco en el curso de la enfermedad. Conclusiones. Los estudios observacionales demuestran que el tabaquismo incrementa de forma significativa el riesgo de EM (odds ratio ~ 1,5) y es un factor de riesgo independiente. Sin embargo, la EM es una enfermedad compleja y el aumento de riesgo por el tabaco puede diferir en funcion de la interaccion con otros factores geneticos y ambientales. El papel del tabaco como factor de progresion es mas controvertido, con resultados contradictorios y estudios de gran variabilidad, lo que dificulta establecer una conclusion firme. Los mecanismos por los que el tabaquismo modifica el riesgo y posiblemente la progresion de la enfermedad no son aun conocidos.

  16. The management of multiple sclerosis in children: a European view

    DEFF Research Database (Denmark)

    Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey;

    2010-01-01

    in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce......About 3-5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity...... in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active...

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

    Directory of Open Access Journals (Sweden)

    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. Alemtuzumab in the treatment of multiple sclerosis

    OpenAIRE

    2014-01-01

    Óscar Fernandez Institute of Clinical Neuroscience, Neurology Department, Hospital Regional Universitario Carlos Haya, FIMABIS, Malaga, Spain Abstract: Alemtuzumab (formerly known as Campath-1H) has recently been approved by the European Medicines Agency for highly-active, relapsing-remitting multiple sclerosis (MS). The molecule targets the CD52 surface glycoprotein on certain T cells and B cells and is thought to exert its effect in MS through a “resetting” o...

  19. [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...... alemtuzumab, daclizumab and rituximab, which have all shown promising results. However, the monoclonal antibodies generally have a less favourable safety profile and are more expensive than the currently used first-line therapies, IFNb and glatiramer acetate Udgivelsesdato: 2008/6/9...

  20. Newer therapies for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Alasdair Coles

    2015-01-01

    Full Text Available The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years, the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an "escalation" or "induction" approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects.

  1. Alemtuzumab therapy for multiple sclerosis.

    Science.gov (United States)

    Coles, Alasdair J

    2013-01-01

    Alemtuzumab is a humanized monoclonal antibody that is administered daily for 5 days, and then no further therapy is required for 12 months. It causes rapid and prolonged lymphocyte depletion; the consequent homeostatic reconstitution leads to a radically reformed lymphocyte pool with a relative increase in regulatory T cells and expansion of autoreactive T cells. Although previously licensed for the treatment of B-cell chronic lymphocytic leukemia, it is now been considered for licensing in the treatment of multiple sclerosis (MS). From a disappointing experience with alemtuzumab in progressive MS, Alastair Compston and I argued that immunotherapies should be given early in the course of the disease. In a unique program of drug development in MS, alemtuzumab has been compared in 1 phase 2 trial and 2 phase 3 trials with the active comparator interferon beta-1a. In all trials, alemtuzumab was more effective in suppressing relapses than interferon beta-1a. In one phase 2 and one phase 3 trial, alemtuzumab also reduced the risk of accumulating disability compared with interferon beta-1a. Indeed, alemtuzumab treatment led to an improvement in disability and a reduction in cerebral atrophy. The safety issues are infusion-associated reactions largely controlled by methylprednisolone, antihistamines, and antipyretics; mild-to-moderate infections (with 3 opportunistic infections from the open-label experience: 1 case each of spirochaetal gingivitis, pyogenic granuloma, and Listeria meningitis); and autoimmunity. Usually autoimmunity is directed against the thyroid gland, but causes (1 %) immune thrombocytopenia, and in a few cases antiglomerular basement membrane syndrome. Alemtuzumab is an effective therapy for early relapsing-remitting MS, offering disability improvement at least to 5 years after treatment. Its use requires careful monitoring so that potentially serious side effects can be treated early and effectively.

  2. Cognitive Impairment in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Farnaz Etesam

    2014-01-01

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

  3. Is Multiple Sclerosis CNS Leprosy?

    Directory of Open Access Journals (Sweden)

    Noha t. Abokrysha

    2008-05-01

    Full Text Available Multiple sclerosis (MS is widely believed to be an autoimmune disorder. Another exciting idea regarding the aetiology of MS may be that the immune response in MS could result from a chronic infection rather than autoimmunity in the usual sense. M. leprae-induced myelin damage in the early infectious process provides valuable insights into the pathologic mechanisms of multiple sclerosis. However, no research has hypothesized the possible involvement of mycobacterium leprae or its components in pathogenesis of MS. Most of the antigens of mycobacterium leprae and mycobacterium tuberculosis are members of stress protein families. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly coded with very similar genes. I hypothesize that MS is a syndrome of diseases, induced by intradermal BCG vaccine which may contain the antigen component resembling that of leprae that can either produce central demyelination by itself, or by delayed hypersensitivity. The hypothesis should be assessed in several experimental and clinical trials. If my hypothesis can be verified experimentally and clinically, then measurements to prevent MS disease could be accomplished.

  4. The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis.

    Science.gov (United States)

    Zhu, Wenjun; Frost, Emma E; Begum, Farhana; Vora, Parvez; Au, Kelvin; Gong, Yuewen; MacNeil, Brian; Pillai, Prakash; Namaka, Mike

    2012-08-01

    Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain-derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post-disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection.

  5. Interhemispheric disconnection effects in multiple sclerosis.

    Science.gov (United States)

    Lindeboom, J; ter Horst, R

    1988-01-01

    Patients with multiple sclerosis reported less left ear numbers but more right ear numbers than controls in a dichotic listening test. The multiple sclerosis patients were also relatively impaired on three learning tasks; one of these, a test for paired-associate learning of names and faces, correlated with left ear findings; the results are interpreted as supporting a hypothesised disconnection mechanism. PMID:3236021

  6. Demyelination of subcortical nuclei in multiple sclerosis

    Science.gov (United States)

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

    2016-02-01

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

  7. Fatal accidents among Danes with multiple sclerosis

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Hansen, Thomas; Koch-Henriksen, Nils

    2006-01-01

    We compared the rate of fatal accidents among Danes with multiple sclerosis (MS) with that of the general population. The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry and covered all 10174 persons in whom MS was diagnosed during the period 1953...

  8. Reproduction and the risk of multiple sclerosis

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. Alemtuzumab in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Fernandez Ó

    2014-02-01

    Full Text Available Óscar Fernandez Institute of Clinical Neuroscience, Neurology Department, Hospital Regional Universitario Carlos Haya, FIMABIS, Malaga, Spain Abstract: Alemtuzumab (formerly known as Campath-1H has recently been approved by the European Medicines Agency for highly-active, relapsing-remitting multiple sclerosis (MS. The molecule targets the CD52 surface glycoprotein on certain T cells and B cells and is thought to exert its effect in MS through a “resetting” of the lymphocyte population. Approval was granted on the strength of two pivotal studies, Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS-1 in the first-line setting and CARE-MS-2 in patients who had failed first-line therapy. In both studies, alemtuzumab significantly reduced the relapse rate compared to the comparator, interferon beta-1a (44 µg given subcutaneously three-times per week (Rebif®. In the first-line study, alemtuzumab was also found to significantly reduce the number of patients with sustained progression compared to interferon beta-1a therapy. Autoimmune disorders represent the major side effect of alemtuzumab therapy although they can be managed by careful monitoring and early treatment. Overall, alemtuzumab is likely to be a valuable addition to the neurologist´s armamentarium for the treatment of relapsing-remitting MS. Keywords: alemtuzumab, multiple sclerosis, new therapies, interferon beta-1a, monoclonal antibody, treatment

  10. Alcohol, coffee, fish, smoking and disease progression in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, M. B.; Haentjens, P.; Nagels, G.; De Keyser, J.

    2012-01-01

    Background: Certain lifestyle factors might influence disease activity in multiple sclerosis (MS). Objectives: To investigate the consumption of alcoholic beverages, caffeinated drinks, fish and cigarette smoking in relation to disability progression in relapsing onset and progressive onset MS. Meth

  11. Chromosomal radiosensitivity in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

  12. CD4 T cell activation and disease activity at onset of multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C;

    2004-01-01

    severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  13. Epigenetic Drugs for Multiple Sclerosis.

    Science.gov (United States)

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

  14. Implicit Memory in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    G. Latchford

    1993-01-01

    Full Text Available A number of neuropsychological studies have revealed that memory problems are relatively common in patients with multiple sclerosis (MS. It may be useful to compare MS with conditions such as Huntington's disease (HD, which have been referred to as subcortical dementia. A characteristic of these conditions may be an impairment in implicit (unconscious memory, but not in explicit (conscious memory. The present study examined the functioning of explicit and implicit memory in MS. Results showed that implicit memory was not significantly impaired in the MS subjects, and that they were impaired on recall but not recognition. A correlation was found between implicit memory performance and disability status in MS patients. Findings also suggest the possibility of long-term priming of implicit memory in the control subjects. The implications of these results are discussed.

  15. Multiple sclerosis, a treatable disease.

    Science.gov (United States)

    Doshi, Anisha; Chataway, Jeremy

    2016-12-01

    This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development.

  16. Neuropsychiatric manifestations of multiple sclerosis.

    Science.gov (United States)

    Diaz-Olavarrieta, C; Cummings, J L; Velazquez, J; Garcia de la Cadena, C

    1999-01-01

    The range of neuropsychiatric symptoms in multiple sclerosis (MS) has not been prospectively assessed. The authors, working at a tertiary medical center in Mexico City, used the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms prospectively in 44 MS patients who were stable between relapses and 25 control subjects of similar age, education, and cognitive function. Neuropsychiatric symptoms were present in 95% of patients and 16% of control subjects. Changes present were depressive symptoms (79%), agitation (40%), anxiety (37%), irritability (35%), apathy (20%), euphoria (13%), disinhibition (13%), hallucinations (10%), aberrant motor behavior (9%), and delusions (7%). The only relationships with MRI were between euphoria and hallucinations and moderately severe MRI abnormalities. The authors conclude that diverse types of neuropsychiatric symptoms are common in MS; symptoms are present between exacerbations; and there are variable correlations with MRI abnormalities.

  17. Gait Variability and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Michael J. Socie

    2013-01-01

    Full Text Available Gait variability, that is, fluctuations in movement during walking, is an indicator of walking function and has been associated with various adverse outcomes such as falls. In this paper, current research concerning gait variability in persons with multiple sclerosis (MS is discussed. It is well established that persons with MS have greater gait variability compared to age and gender matched controls without MS. The reasons for the increase in gait variability are not completely understood. Evidence indicates that disability level, assistive device use, attentional requirement, and fatigue are related to gait variability in persons with MS. Future research should address the time-evolving structure (i.e., temporal characteristics of gait variability, the clinical importance of gait variability, and underlying mechanisms that drive gait variability in individuals with MS.

  18. Limb apraxia in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Rapaić Dragan

    2014-01-01

    Full Text Available Background/Aim. There are almost no studies on apraxia in people with multiple sclerosis. Although the white matter is damaged in MS, it is not the only location in which the pathological changes are present. Demyelinated lesions in the cortex have recently been recognized as important components of multiple sclerosis pathology. The aim of this study was to determine whether apraxia is present among people with MS, and the importance of demographic characteristics and impairment of functional systems at conceptualization and execution of movements. Methods. The experimental group consisted of 30 patients, mean age 51.34 ± 7.70 years. The patients in the experimental group were diagnosed with MS according to the McDonald criteria. The control group consisted of 30 healthy subjects, mean age 50.30 ± 10.47 years. For research purposes, we used the following instruments: Questionnaire for Collecting Demographic Data, Kurtzke Functional Systems Scores, Waterloo-Sunnybrook Apraxia Battery (WatAB. Execution of motion tasks that are a part of the Watwere incorporated in the System for the Observation and Analysis of Motor Behavior. Results. Our study showed that limb apraxia was common in people with MS. Apraxia was present during pantomime in 26.70% of the patients, and during the imitation of movements in 44.80% of the patients. Gender, age, education level, duration of disease and a form of MS did not determine the quality of conceptualization and execution of movements. The time elapsed from the last exacerbation was a determinant of quality of executed movements. Impairments of functional systems predicted impairments of movement execution. The expanded disability scale score correlated with the severity of apraxia. Conclusion. Our study confirm the presence of apraxia in MS. It is necessary to carry out further studies using functional magnetic resonance imaging, as well as the conduct longitudinal studies to determine the precise structure of

  19. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells....... In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13)......., helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death...

  20. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...

  1. [Standartization of MRI studies in multiple sclerosis].

    Science.gov (United States)

    Bryukhov, V V; Krotenkova, I A; Morozova, S N; Krotenkova, M V

    2016-01-01

    The use of magnetic resonance imaging (MRI) in patients with multiple sclerosis has markedly increased in recent years. The main task of the MRI studies after the diagnosis of multiple sclerosis is to assess the dynamics of MRI for determining disease progression and monitoring the efficacy of therapy. In this regard, it is very important to obtain the most identical baseline and follow-up MRI that is possible when a single standard protocol is used. This article presents the protocol of brain MRI and spinal cord MRI and interpretation of MRI studies in patients with multiple sclerosis.

  2. Novel Insights and Therapeutics in Multiple Sclerosis.

    Science.gov (United States)

    Wagner, Catriona A; Goverman, Joan M

    2015-01-01

    The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

  3. Registers of multiple sclerosis in Denmark

    DEFF Research Database (Denmark)

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

    2015-01-01

    There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have...

  4. Nuclear magnetic resonance relaxation in multiple sclerosis

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  5. Regulatory genomic regions active in immune cell types explain a large proportion of the genetic risk of multiple sclerosis.

    Science.gov (United States)

    Elangovan, Ramyiadarsini I; Disanto, Giulio; Berlanga-Taylor, Antonio J; Ramagopalan, Sreeram V; Handunnetthi, Lahiru

    2014-04-01

    There is little understanding of how genetic variants discovered in recent genome-wide association studies are involved in the pathogenesis of multiple sclerosis (MS). We aimed to investigate which chromatin states and cell types explain genetic risk in MS. We used genotype data from 1854 MS patients and 5164 controls produced by the International Multiple Sclerosis Genetics Consortium and Wellcome Trust Case Control Consortium. We estimated the proportion of phenotypic variance between cases and controls explained by cell-specific chromatin state and DNase I hypersensitivity sites (DHSs) using the Genome-wide Complex Trait Analysis software. A large proportion of variance was explained by single-nucleotide polymorphisms (SNPs) in strong enhancer (SE) elements of immortalized B lymphocytes (5.39%). Three independent SNPs located within SE showed suggestive evidence of association with MS: rs12928822 (odds ratio (OR)=0.81, 95% confidence interval (CI)=0.73-0.89, P=2.48E-05), rs727263 (OR=0.75, 95% CI=0.66-0.85, P=3.26E-06) and rs4674923 (OR=0.85, 95% CI=0.79-0.92, P=1.63E-05). Genetic variants located within DHSs of CD19+ B cells explained the greatest proportion of variance. Genetic variants influencing the risk of MS are located within regulatory elements active in immune cells. This study also identifies a number of immune cell types likely to be involved in the causal cascade and that carry important implications for future studies of therapeutic design.

  6. Multiple sclerosis and sexual dysfunction

    Institute of Scientific and Technical Information of China (English)

    Zhen-Ni Guo; Si-Yuan He; Hong-Liang Zhang; Jiang Wu; Yi Yang

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by episodic and progressive neurologic dysfunction resulting from inflammatory and autoimmune reactions.The underlying pathogenesis of MS remains largely unclear.However,it is currently accepted as a T cell-mediated autoimmune disease.Among other clinical manifestations,sexual dysfunction (SD) is a painful but still underreported and underdiagnosed symptom of the disorder.SD in MS patients may result from a complex set of conditions and may be associated with multiple anatomic,physiologic,biologic,medical and psychological factors.SD arises primarily from lesions affecting the neural pathways involved in physiologic function.In addition,psychological factors,the side effects of medications and physical symptoms such as fatigue,muscular weakness,menstrual changes,pain and concerns about bladder and bowel incontinence may also be involved.Since MS primarily affects young people,SD secondary to MS may have a great impact on quality of life.Thus,maintaining a healthy sexual life with MS is an important priority.The treatment of SD requires multidisciplinary teamwork and cooperation among specialists,individual patients,partners and the society.

  7. The relation between inflammation and neurodegeneration in multiple sclerosis brains

    DEFF Research Database (Denmark)

    Frischer, J.M.; Bramow, S.; Dal-Bianco, A.;

    2009-01-01

    Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation...... to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological...... and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimer's or vascular disease. Our study suggests a close association...

  8. Self-efficacy and environmental correlates of physical activity among older women and women with multiple sclerosis.

    Science.gov (United States)

    Morris, Katherine S; McAuley, Edward; Motl, Robert W

    2008-08-01

    Physical inactivity is a major health problem in the United States, particularly in elderly and disabled populations. Little research exists examining the relationships between aspects of the built environment and physical activity in older adults and individuals with multiple sclerosis (MS). We adopted a social cognitive perspective to examine the independent roles of perceptions of the environmental, self-efficacy and functional limitations in understanding physical activity levels among elderly women and women with MS. Older women (n=136) and women diagnosed with MS (n=173) were recruited to participate in separate cross-sectional studies. Individuals completed a battery of questionnaires and wore an activity monitor for 7 days. All measures were issued and collected through the mail with the use of self-addressed, pre-paid envelopes. Initial correlational analyses indicated that self-efficacy, functional limitations and environmental perceptions were significantly related to physical activity. Among older women, self-efficacy, functional limitations and street connectivity demonstrated independent contributions to physical activity behavior. Only self-efficacy and functional limitations demonstrated significant associations among women with MS. The prospective contributions of the environment and individual factors to changes in physical activity need to be determined.

  9. Cognitive impairment in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kutashov V.A.

    2016-06-01

    Full Text Available Aim: to identify the degree of cognitive impairment (CN and to optimize the treatment of patients with multiple sclerosis (MS. Material and methods. A total of 695 patients (278 men and 417 women were ranged from 18 to 63 years. The mean age was 30.2±0.7 years: women (417 28.5±0.5 years, while for men (278 31.8±0.7 years. Relaps-ing-remitting type (RT of MS was established in 520 patients (74.8%, secondary progressive type (VPT MS in 132 patients (18.9% and primary progressive type (PPT MS in 10 patients (1.5%. Clinically isolated syndrome (CIS was detected in 33 patients (4.8%. The diagnosis of MS 662 patients according to the criteria McDonald etal. (2005. Score of neurologic deficit was carried out on an extended scale of disability (Expanded Disability Status Scale — EDSS. CN were evaluated by conventional tests. To estimate the orientation in time, assessment of short-term and long-term memory, attention and concentration, as well as executive functions, memory, language, evaluation of optical-spatial activities, conceptual thinking, the account used by the Montreal Cognitive Assessment Scale (MoCA. For the screening of dementia with a primary lesion of the frontal lobes and subcortical cerebral structures used battery frontal test to assess frontal dysfunction. Results. The ratio of male (265 and female (397 was 1:1.5. The severity of the condition patients EDSS scale ranged from 1.5 to 8.0 points, and the average score was 3.5±1.2. In the group of patients with RT RS average score EDSS was more than a half (2.5±1.1, than in the group of patients with MS VAC (5.5±1.2 and POS PC (6.5±1.2. In the study of history, it was found that the development of the RS (662 patients was preceded by the following conditions: a viral infection in 277 patients (41.84%; fatigue in 147 patients (22.21%; transferred psycho-emotional load from 218 (32.93%; after pregnancy and childbirth in 20 patients (3.02%. Conclusion. Among the patients with MS

  10. Defining the clinical course of multiple sclerosis

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. Epidemiology in multiple sclerosis: a pilgrim's progress.

    Science.gov (United States)

    Kurtzke, John F

    2013-09-01

    There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands

  12. Novel Insights and Therapeutics in Multiple Sclerosis

    OpenAIRE

    Wagner, Catriona A.; Goverman, Joan M.

    2015-01-01

    The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that ma...

  13. Emerging therapies for treatment of multiple sclerosis

    OpenAIRE

    2010-01-01

    John R Corboy, Augusto A MiravalleRocky Mountain Multiple Sclerosis Center, Anschutz Medical Campus, University of Colorado Denver, Aurora, Colorado, USAAbstract: In the last decade, a new armamentarium of immune-based therapies have been developed and tested in patients with multiple sclerosis. Some of these therapies are showing a high level of efficacy, with an acceptable adverse effect profile. Because present therapies have significant limitations in slowing disease progression, require ...

  14. Reproductive history and risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Nete Munk; Jørgensen, Kristian Tore; Stenager, Egon

    2011-01-01

    It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting.......It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting....

  15. Anti-Integrin Therapy for Multiple Sclerosis

    OpenAIRE

    Eiji Kawamoto; Susumu Nakahashi; Takayuki Okamoto; Hiroshi Imai; Motomu Shimaoka

    2012-01-01

    Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper pr...

  16. Alemtuzumab for the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Willis MD

    2015-03-01

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

  17. Polyunsaturated fatty acids for multiple sclerosis treatment

    Directory of Open Access Journals (Sweden)

    Monserrat Kong-González

    2015-01-01

    Full Text Available INTRODUCTION Fatty acids have an important role in structure and function of the nervous system. Recently, epidemiologic studies on neurodegenerative disorders have evaluated the usefulness of polyunsaturated fatty acids on multiple sclerosis. OBJECTIVE To examine recent studies, clinical trials, and reviews on the therapeutic effect of polyunsaturated fatty acids in multiple sclerosis. METHODS We conducted a search in MEDLINE/PubMed and Cochrane Library with the terms "fatty acids", "omega-3" and "omega-6" in combination with "multiple sclerosis". Articles were selected according to their relevance on the topic. RESULTS Epidemiologic studies have shown benefits of dietary supplementation with polyunsaturated fatty acids -especially omega-3- in relation to inflammatory, autoimmune and neurodegenerative disorders. In contrast, the studies do not show a beneficial effect of polyunsaturated fatty acids in multiple sclerosis. However, there are limitations related to design and sample issues in these studies CONCLUSIONS There is some evidence of a protective effect of polyunsaturated fatty acids on the risk of multiple sclerosis. Despite this, to date controlled trials have not produced definite results on the benefits of supplementation with polyunsaturated fatty acids in patients with multiple sclerosis. Any potential benefit will have to be confirmed in the long term.

  18. Recent developments in multiple sclerosis therapeutics

    Directory of Open Access Journals (Sweden)

    Bourdette Dennis

    2009-12-01

    Full Text Available Abstract Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought.

  19. Recent developments in multiple sclerosis therapeutics.

    Science.gov (United States)

    Spain, Rebecca I; Cameron, Michelle H; Bourdette, Dennis

    2009-12-07

    Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-beta, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought.

  20. 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.

  1. Remyelination Therapy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Danielle E. Harlow

    2015-12-01

    Full Text Available Multiple Sclerosis (MS is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in pre-clinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

  2. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  3. Mental toughness, sleep disturbances, and physical activity in patients with multiple sclerosis compared to healthy adolescents and young adults

    Directory of Open Access Journals (Sweden)

    Sadeghi Bahmani D

    2016-06-01

    Full Text Available Dena Sadeghi Bahmani,1 Markus Gerber,2 Nadeem Kalak,1 Sakari Lemola,3 Peter J Clough,4 Pasquale Calabrese,5 Vahid Shaygannejad,6 Uwe Pühse,2 Edith Holsboer-Trachsler,1 Serge Brand1,2 1Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, 2Department of Sport, Exercise and Health, Sport Science Section, University of Basel, Basel, Switzerland; 3Department of Psychology, University of Warwick, Coventry, 4Department of Psychology, Manchester Metropolitan University, Manchester, UK; 5Division of Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland; 6Department of Neurology and Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Background: Multiple sclerosis (MS is the most common chronic autoimmune demyelinating and inflammatory disease of the central nervous system, afflicting both the body and mind. The risk of suffering from MS is 2.5–3.5 times greater in females than in males. While there is extant research on fatigue, depression, and cognitive impairment in patients with MS during its clinical course, there is a lack of research focusing on sleep, psychological functioning, and physical activity (PA at the point of disease onset. The aims of the present study were therefore, to assess the markers of mental toughness (MT as a dimension of psychological functioning, sleep disturbances (SD, and PA among patients at the moment of disease onset and to compare these with the corresponding values for healthy adolescents and young adults. Methods: A total of 23 patients with MS at disease onset (mean age =32.31 years; 91% females, 23 healthy adolescents (mean age =17.43 years; 82% females, and 25 healthy young adults (mean age =20.72 years; 80% females took part in the study. They completed questionnaires covering sociodemographic data, MT, SD, and PA. Results: Patients with MS had similar scores for MT traits as those in healthy

  4. 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.

  5. Iron Chelation and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Kelsey J. Weigel

    2014-01-01

    Full Text Available Histochemical and MRI studies have demonstrated that MS (multiple sclerosis patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

  6. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

    Science.gov (United States)

    Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

    2016-11-23

    Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future.

  7. INCREASED URINARY NEOPTERIN: CREATININE RATIO AS A MARKER OF ACTIVATION OF CELL-MEDIATED IMMUNITY AND OXIDATIVE STRESS IN THE IRANIAN PATIENTS WITH MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    H. Khorami

    2003-09-01

    Full Text Available Neopterin, apyrazinopyrimidine compound, is produced by macrophages after induction by interferon gamma (IFN-y and serves as a marker of cellular immune system activation followed by oxidative stress. The aim of this study was to determine urinary neopterin to creatinine ratio (UNCR as a surrogate marker of cell-mediated immune activation in multiple sclerosis (MS. Three weekly early morning urine samples were collected from 27 patients with MS and 31 age- and sex-matched apparently healthy subjects. Urinary neopterin and creatinine were determined using reversed phase high-performance liquid chromatography and Jaffe reaction, respectively. UNCR was significantly higher in patients than in healthy controls indicating IFN-y-induced cellular immunity activation and oxidative stress in multiple sclerosis. As a non-invasive method, UNCR determination may be helpful in monitoring disease progression and the effects of therapies, as well.

  8. Activation of cannabinoid CB2 receptors reduces hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

    Science.gov (United States)

    Fu, Weisi; Taylor, Bradley K

    2015-05-19

    Clinical trials investigating the analgesic efficacy of cannabinoids in multiple sclerosis have yielded mixed results, possibly due to psychotropic side effects mediated by cannabinoid CB1 receptors. We hypothesized that, a CB2-specific agonist (JWH-133) would decrease hyperalgesia in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. Four weeks after induction of experimental autoimmune encephalomyelitis, we found that intrathecal administration of JWH-133 (10-100μg) dose-dependently reduced both mechanical and cold hypersensitivity without producing signs of sedation or ataxia. The anti-hyperalgesic effects of JWH-133 could be dose-dependently prevented by intrathecal co-administration of the CB2 antagonist, AM-630 (1-3μg). Our results suggest that JWH-133 acts at CB2 receptors, most likely within the dorsal horn of the spinal cord, to suppress the hypersensitivity associated with experimental autoimmune encephalomyelitis. These are the first pre-clinical studies to directly promote CB2 as a promising target for the treatment of central pain in an animal model of multiple sclerosis.

  9. The impact of an online Facebook support group for people with multiple sclerosis on non-active users

    Directory of Open Access Journals (Sweden)

    Jacqui Steadman

    2014-04-01

    Full Text Available Background: Multiple sclerosis (MS is a debilitating disease and there is little research on support networks for people with MS (PwMS. More specifically, most studies on online support groups focus on those who actively participate in the group, whereas the majority of those who utilise online support groups do so in a passive way.Objectives: This study therefore aimed to explore the experiences of non-active users of an online Facebook support group for PwMS. Emphasis was placed on the facilitators and the barriers that were associated with membership to this group.Method: An exploratory qualitative research design was implemented, whereby thematic analysis was utilised to examine the ten semi-structured interviews that were conducted.Results: Several facilitators were acquired through the online support group; namely emotional support (constant source of support, exposure to negative aspects of the disease,informational support (group as a source of knowledge, quality of information and social companionship (place of belonging. Some barriers were also identified; namely emotional support (emotions lost online, response to messages, exposure to negative aspects of the disease, informational support (information posted on the group, misuse of group and social companionship (non-active status.Conclusion: These findings demonstrate that the non-active members of the online support group for PwMS have valid reasons for their non-active membership status. More important,the findings suggest that the online Facebook support group provided the group members with an important support network in the form of emotional support, informational support and social companionship, despite their non-active membership status or the barriers that have been identified.

  10. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    Science.gov (United States)

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  11. Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis

    Science.gov (United States)

    Passerini, Gabriella; Sangalli, Francesca; Moiola, Lucia; Colombo, Bruno; Locatelli, Massimo; Comi, Giancarlo

    2016-01-01

    Background. The presence of CSF oligoclonal bands (OBs) is an independent prognostic factor for multiple sclerosis (MS), but the difficulties in the standardization of the test and the interlaboratory variation in reporting have contributed to its limited use in the diagnosis of the disease. Standard nephelometric assays to measure free light chains (FLC) levels have been recently developed and the test may improve the detection of intrathecal B cells activity. Methods. The presence of OBs, kappa and lambda FLC levels, and standard indices of intrathecal inflammation were assessed in 100 consecutive patients, including patients with MS, clinically isolated syndromes (CIS), other inflammatory diseases of the CNS, and other noninflammatory diseases. Results. Both KFLC and LFLC correlated strongly with the presence of OCBs and with all common tests for intrathecal inflammation (p < 0.001 for all comparisons). KFLC and LFLC were significantly different in patients with MS and CIS compared to the other groups (p < 0.001 and p < 0.001, resp.) and had a better diagnostic accuracy than all the other tests (area under the curve 82.3 % for KFLC index and 79.3 % for LFLC index). Conclusion. Nephelometric assays for KFLC in CSF reliably detect intrathecal immunoglobulin synthesis and discriminate MS patients. PMID:28116160

  12. Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Gabriella Passerini

    2016-01-01

    Full Text Available Background. The presence of CSF oligoclonal bands (OBs is an independent prognostic factor for multiple sclerosis (MS, but the difficulties in the standardization of the test and the interlaboratory variation in reporting have contributed to its limited use in the diagnosis of the disease. Standard nephelometric assays to measure free light chains (FLC levels have been recently developed and the test may improve the detection of intrathecal B cells activity. Methods. The presence of OBs, kappa and lambda FLC levels, and standard indices of intrathecal inflammation were assessed in 100 consecutive patients, including patients with MS, clinically isolated syndromes (CIS, other inflammatory diseases of the CNS, and other noninflammatory diseases. Results. Both KFLC and LFLC correlated strongly with the presence of OCBs and with all common tests for intrathecal inflammation (p<0.001 for all comparisons. KFLC and LFLC were significantly different in patients with MS and CIS compared to the other groups (p<0.001 and p<0.001, resp. and had a better diagnostic accuracy than all the other tests (area under the curve 82.3 % for KFLC index and 79.3 % for LFLC index. Conclusion. Nephelometric assays for KFLC in CSF reliably detect intrathecal immunoglobulin synthesis and discriminate MS patients.

  13. CD40-mediated NFκB activation in B cells is increased in multiple sclerosis and modulated by therapeutics1

    Science.gov (United States)

    Chen, Ding; Ireland, Sara J.; Remington, Gina; Alvarez, Enrique; Racke, Michael K.; Greenberg, Benjamin; Frohman, Elliot M.; Monson, Nancy L.

    2017-01-01

    CD40 interacts with CD40 ligand and plays an essential role in immune regulation and homeostasis. Recent research findings, however, support a pathogenic role of CD40 in a number of autoimmune diseases. We previously showed that memory B cells from relapsing-remitting multiple sclerosis (RRMS) patients exhibited enhanced proliferation with CD40 stimulation compared to healthy donors. In this study, we used a multi-parameter phosflow approach to analyze the phosphorylation status of NFκB and three major MAP kinases (P38, ERK and JNK), the essential components of signaling pathways downstream of CD40 engagement in B cells from MS patients. We found that memory and naïve B cells from RRMS and secondary progressive MS (SPMS) patients exhibited a significantly elevated level of phosphorylated NFκB (p-P65) following CD40 stimulation compared to healthy donor controls. Combination therapy with interferon beta-1a (Avonex) and mycophenolate mofetil (Cellcept) modulated the hyper-phosphorylation of P65 in B cells of RRMS patients at levels similar to healthy donor controls. Lower disease activity after the combination therapy correlated with the reduced phosphorylation of P65 following CD40 stimulation in treated patients. In addition, glatiramer acetate (GA) treatment also significantly reduced CD40-mediated P65 phosphorylation in RRMS patients, suggesting that reducing CD40-mediated p-P65 induction may be a general mechanism by which some current therapies modulate MS disease. PMID:27798157

  14. Trichurs suis ova theraphy in relapsing multiple sclerosis is safe but without signals of beneficial effect

    DEFF Research Database (Denmark)

    Voldsgaard, A.; Bager, P.; Garde, E.;

    2015-01-01

    BACKGROUND: An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. OBJECTIVE: To evaluate the safety and efficacy on MRI activity of treatment with ...... not change. CONCLUSIONS: In a small group of relapsing multiple sclerosis patients, Trichuris suis oral therapy was well tolerated but without beneficial effect.......BACKGROUND: An observational study has suggested that relapsing-remitting multiple sclerosis patients with helminth infections have lower disease activity and progression than uninfected multiple sclerosis patients. OBJECTIVE: To evaluate the safety and efficacy on MRI activity of treatment...... with TSO in relapsing MS. METHODS: The study was an open-label, magnetic resonance imaging assessor-blinded, baseline-to-treatment study including ten patients with relapsing forms of multiple sclerosis. Median (range) age was 41 (24-55) years, disease duration 9 (4-34) years, Expanded Disability Status...

  15. Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

    Science.gov (United States)

    Rodi, Maria; Dimisianos, Nikolaos; de Lastic, Anne-Lise; Sakellaraki, Panagiota; Deraos, George; Matsoukas, John; Papathanasopoulos, Panagiotis; Mouzaki, Athanasia

    2016-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA−G+ and CD3+CD8+CD28− RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction. PMID:27571060

  16. Therapeutic use of sport climbing for patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Ana Ožura

    2009-05-01

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

  17. Role of Chlamydia in Multiple Sclerosis.

    Science.gov (United States)

    Ivanova, M V; Kolkova, N I; Morgunova, E Yu; Pashko, Yu P; Zigangirova, N A; Zakharova, M N

    2015-09-01

    Chlamydia and antibodies to them were detected by serological, molecular biological, and culture methods in the sera and cerebrospinal fluid of patients with multiple sclerosis and in the reference groups of subjects without neurological diseases. Correlations between the agent presence in the biological fluids of patients and clinical characteristics of the disease were analyzed. C. pneumoniae were more incident in the biological liquids of patients with multiple sclerosis than in healthy volunteers. On the other hand, the incidence of the agent in the patients was not high and its presence did not correlate with the clinical manifestations. C. trachomatis was equally rare in the patients and volunteers. The studies indicated the existence of a group of patients infected by C. pneumoniae in the cohort of patients with multiple sclerosis, but the impact of this agent for the disease course remains unclear.

  18. Current and Future Therapies for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Alireza Minagar

    2013-01-01

    Full Text Available With the introduction of interferon-β1b in 1993 as the first FDA-approved treatment for multiple sclerosis, the era of treatment of this incurable disease began, and its natural course was permanently changed. Currently, seven different treatments for patients with multiple sclerosis with different mechanisms of action and dissimilar side effect profiles exist. These medications include interferon-β1a intramuscular (Avonex, interferon-β1a subcutaneous (Rebif, interferon-β1b subcutaneous (Betaseron/Extavia, glatiramer acetate (Copaxone, natalizumab (Tysabri, fingolimod (Gilenya, teriflunomide (Aubagio, and mitoxantrone (Novantrone. In addition, a large number of clinical trials are being conducted to assess the safety and efficacy of various experimental agents in patients with multiple sclerosis, including alemtuzumab, dimethyl fumarate, laquinimod, rituximab, daclizumab, and cladribine. In this paper, the author presents a concise and comprehensive review of present and potential treatments for this incurable disease.

  19. The nature of caregiving in children of a parent with multiple sclerosis from multiple sources and the associations between caregiving activities and youth adjustment overtime.

    Science.gov (United States)

    Pakenham, Kenneth I; Cox, Stephen

    2012-01-01

    This study explored youth caregiving for a parent with multiple sclerosis (MS) from multiple perspectives, and examined associations between caregiving and child negative (behavioural emotional difficulties, somatisation) and positive (life satisfaction, positive affect, prosocial behaviour) adjustment outcomes overtime. A total of 88 families participated; 85 parents with MS, 55 partners and 130 children completed questionnaires at Time 1. Child caregiving was assessed by the Youth Activities of Caregiving Scale (YACS). Child and parent questionnaire data were collected at Time 1 and child data were collected 12 months later (Time 2). Factor analysis of the child and parent YACS data replicated the four factors (instrumental, social-emotional, personal-intimate, domestic-household care), all of which were psychometrically sound. The YACS factors were related to parental illness and caregiving context variables that reflected increased caregiving demands. The Time 1 instrumental and social-emotional care domains were associated with poorer Time 2 adjustment, whereas personal-intimate was related to better adjustment and domestic-household care was unrelated to adjustment. Children and their parents exhibited highest agreement on personal-intimate, instrumental and total caregiving, and least on domestic-household and social-emotional care. Findings delineate the key dimensions of young caregiving in MS and the differential links between caregiving activities and youth adjustment.

  20. New management algorithms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg

    2014-01-01

    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...... 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...

  1. Reproductive History and Risk of Multiple Sclerosis

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. The Danish Multiple Sclerosis Treatment Register

    DEFF Research Database (Denmark)

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

    2016-01-01

    AIM OF THE DATABASE: The Danish Multiple Sclerosis Treatment Register (DMSTR) serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. STUDY POPULATION......: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular...

  3. Cardiointervalography in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    A. R. Rakhmatullin

    2016-01-01

    Full Text Available Cardiovascular autonomic symptoms significantly impart quality of life in patients with multiple sclerosis (MR and, in some cases, pose a threat to their life.Objective: to study cardiovascular autonomic dysfunction by cardiointervalography in MS patients.Patients and methods. Cardiovascular tests (CVT were carried out in 47 patients with MS (a study group and in 22 healthy individuals (a control group.Results. Comparative analysis revealed a significant reduction in the values of basic CVTs (Cresp, C30:15, and CVals in MS patients (p<0.05. The isometric contraction test showed a statistically significant decrease in diastolic blood pressure; a severe lesion of the segmental area of the autonomic nervous system was detected in 45% of cases.Conclusion. A significant decrease in vagal and sympathetic activities was recorded in patients with MS.

  4. Biological markers in multiple sclerosis related to disease activity and progression

    NARCIS (Netherlands)

    Eikelenboom, M.J.

    2007-01-01

    Ziekteactiviteit bij multiple sclerose meten in lichaamsvloeistoffen MJ Eikelenboom Multipele sclerose (MS) is een chronische aandoening van het centraal zenuwstelsel. Bij mensen met MS ontstaan er ontstekingen in de hersenen en het ruggenmerg, waardoor de zenuwen niet meer goed werken. Het verst

  5. Underlying cause of death in Danish patients with multiple sclerosis

    DEFF Research Database (Denmark)

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

    1998-01-01

    To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis.......To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis....

  6. Randomized trial of oral teriflunomide for relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    O'Connor, Paul; Wolinsky, Jerry S; Confavreux, Christian;

    2011-01-01

    Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis.......Teriflunomide is a new oral disease-modifying therapy for relapsing forms of multiple sclerosis....

  7. Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients.

    Science.gov (United States)

    Hartl, Christina; Obermeier, Viola; Gerdes, Lisa Ann; Brügel, Mathias; von Kries, Rüdiger; Kümpfel, Tania

    2017-04-15

    Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. The mean 25-(OH)-D serum concentration was 24.8ng/ml (range 8.3-140ng/ml) with peak levels of 32.2ng/ml in July/August and nadir in January/February (17.2ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

  8. Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions.

    Science.gov (United States)

    De Groot, C J; Bergers, E; Kamphorst, W; Ravid, R; Polman, C H; Barkhof, F; van der Valk, P

    2001-08-01

    Macroscopic sampling of multiple sclerosis lesions in the brain tends to find chronic lesions. For a better understanding of the dynamics of the multiple sclerosis disease process, research into new and developing lesions is of great interest. As MRI in vivo effectively demonstrates lesions in multiple sclerosis patients, we have applied it to unfixed post-mortem brain slices to identify abnormalities, in order to obtain a higher yield of active lesions. The Netherlands Brain Bank organized the rapid autopsy of 29 multiple sclerosis patients. The brain was cut in 1 cm coronal slices. One or two slices were subjected to T(1)- and T(2)-weighted MRI, and then cut at the plane of the MRI scan into 5 mm thick opposing sections. Areas of interest were identified based on the MRI findings and excised. One half was fixed in 10% formalin and paraffin-embedded, and the corresponding area in the adjacent half was snap-frozen in liquid nitrogen. In total, 136 out of 174 brain tissue samples could be matched with the abnormalities seen on T(2)-weighted MRIs. The stage of lesional development was determined (immuno) histochemically. For 54 MRI-detectable samples, it was recorded whether they were macroscopically detectable, i.e. visible and/or palpable. Histopathological analysis revealed that 48% of the hyperintense areas seen on T(2)-weighted images represented active lesions, including lesions localized in the normal appearing white matter, without apparent loss of myelin but nevertheless showing a variable degree of oedema, small clusters of microglial cells with enhanced major histocompatibility complex class II antigen, CD45 and CD68 antigen expression and a variable number of perivascular lymphocytes around small blood vessels [designated as (p)reactive lesions]. From the macroscopically not-visible/not-palpable MRI-detected abnormalities, 58% were (p)reactive lesions and 21% contained active demyelinating lesions. In contrast, visible and/or palpable brain tissue samples

  9. BAYESIAN NETWORKS FOR SUB-GROUPS OF MULTIPLE SCLEROSIS

    OpenAIRE

    2013-01-01

    In this study, patients with multiple sclerosis "sub-groups" characteristics in relation to detection of a statistically (SPSS) and are provided in the Bayesian network. The main objective of this study, regarding the appearance of MRI lesions in patients with Multiple Sclerosis information and / or EDSS scores to investigate the possible attack of multiple sclerosis subgroups. Bayesian networks, reflects the level of sub-groups in multiple sclerosis patients. Analyzes were conducted...

  10. PPAR-γ: Therapeutic Potential for Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Paul D. Drew

    2008-01-01

    Full Text Available The role of peroxisome proliferator-activated receptors (PPARs in altering lipid and glucose metabolism is well established. More recent studies indicate that PPARs also play critical roles in controlling immune responses. We and others have previously demonstrated that PPAR-γ agonists modulate the development of experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. This review will discuss the cellular and molecular mechanisms by which these agonists are believed to modulate disease. The therapeutic potential of PPAR-γ agonists in the treatment of multiple sclerosis will also be considered.

  11. Development of a Novel Microfluidic Platform for Multiple Sclerosis Study

    Science.gov (United States)

    2012-08-01

    Platform for Multiple Sclerosis Study PRINCIPAL INVESTIGATOR: In Hong Yang CONTRACTING ORGANIZATION: Johns Hopkins University...COVERED 15 Jul 2011 - 14 Jul 2012 4. TITLE AND SUBTITLE Development of a Novel Microfluidic Platform for Multiple Sclerosis Study 5a. CONTRACT NUMBER...NSC in the pathology and therapy of neurodegenerative disorders including multiple sclerosis (MS) [1-2]. Evidence suggests that NSC proliferation

  12. Leisure time activities of Iranian patients with multiple sclerosis: a qualitative study

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Sadegh Hosseini

    2016-03-01

    Conclusion: The results represented the range and heterogeneity of leisure activities amongst the MS patients. Considering participation in spiritual/religious and social activities as leisure time undertaking might reflect cultural diversity in the perception and use of time for recreation. For mental health promotion purposes, paying special attention to the types of activities that people of different socio-cultural background choose for their refreshment could help health care providers in giving tailored advice for patients with MS and other chronic debilitating disease.

  13. Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance

    Directory of Open Access Journals (Sweden)

    Hundeshagen Alexander

    2012-06-01

    Full Text Available Abstract Background A subset of patients with multiple sclerosis (MS shows an increased endogenous IFN-like activity before initiation of IFN-beta treatment. The molecular basis of this phenomenon and its relevance to predict individual therapy outcomes are not yet fully understood. We studied the expression patterns of these patients, the prognostic value of an elevated IFN-like activity, and the gene regulatory effects of exogenously administered IFN-beta. Methods Microarray gene expression profiling was performed for 61 MS patients using peripheral blood mononuclear cells obtained before and after 1 month of IFN-beta therapy. Expression levels of genes involved in pathways either inducing or being activated by IFN-beta were compared between patients with high (MX1high cohort and low (MX1low cohort endogenous IFN-like activity. Patients were followed for 5 years and relapses as well as progression on the expanded disability status scale (EDSS were documented. Results Before the start of therapy, 11 patients presented elevated mRNA levels of IFN-stimulated genes indicative of a relatively high endogenous IFN-like activity (MX1high. In these patients, pathogen receptors (for example, TLR7, RIG-I and IFIH1 and transcription factors were also expressed more strongly, which could be attributed to an overactivity of IFN-stimulated gene factor 3 (ISGF3, a complex formed by STAT1, STAT2 and IFN regulatory factor 9. After 1 month of IFN-beta therapy, the expression of many pathway genes was significantly induced in MX1low patients, but remained unaltered in MX1high patients. During follow-up, relapse rate and changes in EDSS were comparable between both patient groups, with differences seen between different types of IFN-beta drug application. Conclusions Therapeutic IFN-beta induces the transcription of several genes involved in IFN-related pathways. In a subgroup of MS patients, the expression of these genes is already increased before therapy

  14. Pharmacological inhibition of MALT1 protease activity protects mice in a mouse model of multiple sclerosis

    OpenAIRE

    Mc Guire, Conor; Elton, Lynn; Wieghofer, Peter; Staal, Jens; Voet, Sofie; Demeyer, Annelies; Nagel, Daniel; Krappmann, Daniel; Prinz, Marco; Beyaert, Rudi; van Loo, Geert

    2014-01-01

    Background: The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is crucial for lymphocyte activation through signaling to the transcription factor NF-kappa B. Besides functioning as a scaffold signaling protein, MALT1 also acts as a cysteine protease that specifically cleaves a number of substrates and contributes to specific T cell receptor-induced gene expression. Recently, small molecule inhibitors of MALT1 proteolytic activity were identified and sho...

  15. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

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

  16. Treatment of seizures in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus W.; Polman, Susanne K. L.; Uyttenboogaart, Maarten; De Keyser, Jacques

    2009-01-01

    Background Epileptic seizures occur in only a minority of patients with multiple sclerosis (MS), but can have serious consequences. The available literature suggests an association of seizures in MS with cortical and subcortical demyelinating lesions, which suggest that seizures in MS are probably m

  17. Myeloproliferative neoplasms in five multiple sclerosis patients

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis

    2013-01-01

    The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007-2012. We describe the patients' history and treatment...

  18. Fatigue, depression and progression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M.; Uyttenboogaart, Maarten; van Harten, A.; Heerings, M.; De Keyser, J.

    2008-01-01

    Objective To investigate the effect of fatigue and depression on disease progression in multiple sclerosis (MS), and the long-term prognosis of these symptoms. Methods 228 patients with MS were investigated for fatigue and depression with the Fatigue Severity Scale (FSS) and Center for Epidemiologic

  19. Exercise therapy for fatigue in multiple sclerosis

    NARCIS (Netherlands)

    Heine, Martin; van de Port, Ingrid; Rietberg, Marc B; van Wegen, Erwin Eh; Kwakkel, Gert

    2015-01-01

    BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system affecting an estimated 1.3 million people worldwide. It is characterised by a variety of disabling symptoms of which excessive fatigue is the most frequent. Fatigue is often reported as the most invalidat

  20. Treating fatigue in multiple sclerosis : Aerobic training

    NARCIS (Netherlands)

    Heine, M

    2016-01-01

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

  1. The risk of multiple sclerosis in nurses

    DEFF Research Database (Denmark)

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

    2003-01-01

    The incidence of multiple sclerosis (MS) in nurses during the period 1980-1996 was calculated in a nationwide study. The cohort consisted of 69,428 nurses, 2185 men and 67,243 women. Sixty (two men and 58 women) with definite MS were observed, whereas 69.3 were expected. We found no significant...

  2. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  3. Onset symptoms in paediatric multiple sclerosis

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  4. Pharmacological management of spasticity in multiple sclerosis

    DEFF Research Database (Denmark)

    Otero-Romero, Susana; Sastre-Garriga, Jaume; Comi, Giancarlo

    2016-01-01

    BACKGROUND AND OBJECTIVES: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. METHODS...

  5. Antigen-specific therapies in multiple sclerosis

    NARCIS (Netherlands)

    Noort, J.M. van

    1998-01-01

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

  6. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

  7. The socioeconomic consequences of multiple sclerosis

    DEFF Research Database (Denmark)

    Jennum, Poul; Wanscher, Benedikte; Frederiksen, Jette

    2012-01-01

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

  8. Etiology and pathogenesis of multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M

    1998-01-01

    The cause of multiple sclerosis (MS) remains unknown despite decades of intense research. The major research disciplines that have been brought to bear on this question include genetics, epidemiology, neuropathology, immunology, and virology. Recent advances in the understanding of the inflammatory...

  9. Risk factors for suicide in multiple sclerosis

    DEFF Research Database (Denmark)

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

    1996-01-01

    BACKGROUND: The purpose of the present study was to identify risk factors for suicide in patients with multiple sclerosis (MS). METHODS: The study is based on available information about MS patients identified in the Danish MS Registry (DMSR) with onset in the period 1950-1985. We compared the MS...

  10. Psychiatric co-morbidity in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. Concordance for multiple sclerosis in Danish twins

    DEFF Research Database (Denmark)

    Hansen, T; Skytthe, Axel; Stenager, Egon

    2005-01-01

    The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study...

  12. High Intensity Exercise in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Wens, Inez; Dalgas, Ulrik; Vandenabeele, Frank

    2015-01-01

    Introduction Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown. Methods Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2...

  13. Gender and autoimmune comorbidity in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C

    2014-01-01

    BACKGROUND: The female preponderance in incidence of multiple sclerosis (MS) calls for investigations into sex differences in comorbidity with other autoimmune diseases (ADs). OBJECTIVES: To determine whether male and female patients with MS have a higher frequency of autoimmune comorbidity than...

  14. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Vasilii B Doronin

    Full Text Available We have recently shown that IgGs from serum and cerebrospinal fluid (CSF of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.

  15. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Daniela F Angelini

    Full Text Available It has long been known that multiple sclerosis (MS is associated with an increased Epstein-Barr virus (EBV seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A and lytic (BZLF-1, BMLF-1 antigens in relapsing-remitting MS patients (n = 113 and healthy donors (HD (n = 43 and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

  16. Endothelial microparticles (EMP) bind and activate monocytes: elevated EMP-monocyte conjugates in multiple sclerosis.

    Science.gov (United States)

    Jy, Wenche; Minagar, Alireza; Jimenez, Joaquin J; Sheremata, William A; Mauro, Lucia M; Horstman, Lawrence L; Bidot, Carlos; Ahn, Yeon S

    2004-09-01

    Elevated plasma endothelial microparticles (EMP) have been documented in MS during exacerbation. However, the role of EMP in pathogenesis of MS remains unclear. We investigated the formation of EMP-monocyte conjugates (EMP-MoC) and their potential role in transendothelial migration of inflammatory cells in MS. EMP-MoC were assayed in 30 MS patients in exacerbation, 20 in remission and in 35 controls. EMP-leukocyte conjugation was investigated flowcytometrically by employing alpha-CD54 or alpha-CD62E for EMP, and alpha-CD45 for leukocytes. EMP-MoC were characterized by identifying adhesion molecules involved and their effect on monocyte function. In vivo (clinical): EMP-MoC were markedly elevated in exacerbation vs. remission and controls, correlating with presence of GD+ MRI lesions. Free CD54+ EMP were not elevated but free CD62E+ EMP were. In vitro: EMP bound preferentially to monocytes, less to neutrophils, but little to lymphocytes. Bound EMP activated monocytes: CD11b expression increased 50% and migration through cerebral endothelial cell layer increased 2.6-fold. Blockade of CD54 reduced binding by 80%. Most CD54+ EMP bound to monocytes, leaving little free EMP, while CD62+ EMP were found both free and bound. These results demonstrated that phenotypic subsets of EMP interacted differently with monocytes. Based on our observations, EMP may enhance inflammation and increase transendothelial migration of monocytes in MS by binding to and activating monocytes through CD54. EMP-MoC were markedly increased in MS patients in exacerbation compared to remission and may serve as a sensitive marker of MS disease activity.

  17. An observational study of alemtuzumab following fingolimod for multiple sclerosis

    DEFF Research Database (Denmark)

    Willis, Mark; Pearson, Owen; Illes, Zsolt

    2017-01-01

    OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod then a...

  18. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  19. Biomarkers in Multiple Sclerosis: Role of Antibodies

    OpenAIRE

    Thomas Berger; Markus Reindl

    2006-01-01

    The first international workshop on “Biomarkers in Multiple Sclerosis” was organized by B. Bielekova, R. Hohlfeld, R. Martin and U. Utz from April 14–16, 2004, in Washington, DC. The workshop intended to discuss the current status and potential applicability of biological markers for the understanding of the pathogenesis, diagnosis, and therapy of multiple sclerosis. The present review summarizes the presentation on the potential role of antibodies as biomarkers for diagnosis, disease activit...

  20. Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Hartung, Hans-Peter; Aktas, Orhan; Boyko, Alexey N

    2015-01-01

    Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing-remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). Important adverse events were infusion-associated reactions, serious infections and autoimmune events. A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab's mechanism of action, pharmacodynamics and opportunities for future research are discussed.

  1. Secondary Progressive Multiple Sclerosis: Definition and Measurement.

    Science.gov (United States)

    Plantone, Domenico; De Angelis, Floriana; Doshi, Anisha; Chataway, Jeremy

    2016-06-01

    Secondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing-remitting (RR) phase. Our incomplete understanding of the pathological mechanisms underlying neurodegeneration in multiple sclerosis (MS) may explain why, to date, there is no definitive imaging or laboratory test that is able to inform us when the disease is clearly entering into a progressive phase and why the vast majority of clinical trials testing immunosuppressant and immunomodulating drugs in SPMS patients has so far yielded disappointing or mixed results. Here we discuss the definition(s) of SPMS and how it may vary, outcome measurements (current and emerging) and modern trial design.

  2. SOME NEUROCHEMICAL DISTURBANCES IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Vladimir V. Markelov

    2006-04-01

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

  3. Type 1 diabetes and multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Nete M; Westergaard, Tine; Frisch, Morten

    2006-01-01

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

  4. Sibship characteristics and risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Bager, Peter; Nielsen, Nete Munk; Bihrmann, Kristine

    2006-01-01

    It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common...... infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935. Persons diagnosed with MS during the period 1968-1998 were identified through linkage with the Danish Multiple...... Sclerosis Register. The cohort of 1.9 million Danes was followed for 28.1 million person-years; during that time, 1,036 persons developed MS. Overall, there was no association between number of older siblings, number of younger siblings, total number of siblings, age distance from the nearest younger...

  5. Paroxysmal ataxia and dysarthria in multiple sclerosis.

    Science.gov (United States)

    Iorio, R; Capone, F; Plantone, D; Batocchi, A P

    2014-01-01

    Paroxysmal ataxia and dysarthria are part of the spectrum of transient neurological disturbances that can be frequently encountered in multiple sclerosis (MS). Prompt recognition of these symptoms is important because they can be the only manifestation of a MS relapse and symptomatic therapy is often beneficial. We report a patient who developed paroxysmal ataxia and dysarthria, documented by video imaging, while he was recovering from a MS relapse. Treatment with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and dysarthria.

  6. Diagnosis and management of multiple sclerosis.

    Science.gov (United States)

    Calabresi, Peter A

    2004-11-15

    Multiple sclerosis, an idiopathic inflammatory disease of the central nervous system, is characterized pathologically by demyelination and subsequent axonal degeneration. The disease commonly presents in young adults and affects twice as many women as men. Common presenting symptoms include numbness, weakness, visual impairment, loss of balance, dizziness, urinary bladder urgency, fatigue, and depression. The diagnosis of multiple sclerosis should be made by a physician with experience in identifying the disease. Diagnosis should be based on objective evidence of two or more neurologic signs that are localized to the brain or spinal cord and are disseminated in time and space (i.e., occur in different parts of the central nervous system at least three months apart). Magnetic resonance imaging with gadolinium contrast, especially during or following a first attack, can be helpful in providing evidence of lesions in other parts of the brain and spinal cord. A second magnetic resonance scan may be useful at least three months after the initial attack to identify new lesions and provide evidence of dissemination over time. It is critical to exclude other diseases that can mimic multiple sclerosis, including vascular disease, spinal cord compression, vitamin B12 deficiency, central nervous system infection (e.g., Lyme disease, syphilis), and other inflammatory conditions (e.g., sarcoidosis, systemic lupus erythematosus, Sjögren's syndrome). Symptom-specific drugs can relieve spasticity, bladder dysfunction, depression, and fatigue. Five disease-modifying treatments for multiple sclerosis have been approved by the U.S. Food and Drug Administration. These treatments are partially effective in reducing exacerbations and may slow progression of disability.

  7. Natalizumab in the treatment of multiple sclerosis

    OpenAIRE

    Brown, Brandon A

    2009-01-01

    Brandon A BrownDepartment of Pharmacy, Brigham and Women’s Hospital, Boston, MA, USAAbstract: Natalizumab is a monoclonal antibody, representing a new class of medication for treating relapsing multiple sclerosis (MS). Conventional treatments include interferons, glatiramer acetate and chemotherapies such as mitoxantrone and cyclophosphamide. These therapies offer only modest clinical benefits and are commonly not tolerated due to side effects. Natalizumab has been proven in large-s...

  8. Natalizumab in the Treatment of Multiple Sclerosis

    OpenAIRE

    Yaldizli, Özgür; Putzki, Norman

    2009-01-01

    Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42-54% over 2 years in its pivotal phase III trial (AFFIRM) in relapsing-remitting multiple sclerosis (RRMS). Natalizumab is generally well tolerated, but due to rare and potentially fatal side-effects, it was approved with a restricted-distribution format in 2006. ...

  9. Auditory evoked potentials and multiple sclerosis

    OpenAIRE

    Carla Gentile Matas; Sandro Luiz de Andrade Matas; Caroline Rondina Salzano de Oliveira; Isabela Crivellaro Gonçalves

    2010-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease that can affect several areas of the central nervous system. Damage along the auditory pathway can alter its integrity significantly. Therefore, it is important to investigate the auditory pathway, from the brainstem to the cortex, in individuals with MS. OBJECTIVE: The aim of this study was to characterize auditory evoked potentials in adults with MS of the remittent-recurrent type. METHOD: The study comprised 25 individuals w...

  10. Gray matter pathology and multiple sclerosis.

    Science.gov (United States)

    Wegner, Christiane; Stadelmann, Christine

    2009-09-01

    Gray matter demyelination is frequent and extensive in most patients with multiple sclerosis (MS) and has recently received much attention in neuropathologic and imaging studies. Gray matter lesions show distinct pathologic features that make their detection difficult with conventional imaging techniques. Thus, despite their high prevalence, their impact on clinical symptoms has not been defined well so far. This review focuses on recent information from pathologic and imaging studies and summarizes our current knowledge on cortical pathology derived from human and experimental studies.

  11. Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Pryce, Gareth; Baker, David

    2015-01-01

    There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.

  12. The genetic aspects of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Sawcer Stephen

    2009-01-01

    Full Text Available The epidemiology of multiple sclerosis has been extensively investigated and two features have consistently emerged: marked geographical variation in prevalence and substantial familial clustering. At first sight, geographic variation would seem to imply an environmental cause for the disease, while familial clustering would seem to suggest that genetic factors have the predominant etiological effect. However, given that geographic variation in prevalence could result from variation in the frequency of genetic risk alleles and that familial clustering might result from shared environmental exposure rather than shared genetic risk alleles, it is clear that these crude inferences are unreliable. Epidemiologists have been resourceful in their attempts to resolve this apparent conflict between "nurture and nature" and have employed a whole variety of sophisticated methods to try and untangle the etiology of multiple sclerosis. The body of evidence that has emerged from these efforts has formed the foundation for decades of research seeking to identify relevant genes and this is the obvious place to start any consideration of the genetics of multiple sclerosis.

  13. Disease modifying therapies for relapsing multiple sclerosis.

    Science.gov (United States)

    Wingerchuk, Dean M; Weinshenker, Brian G

    2016-08-22

    Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.

  14. Fatigue in Multiple Sclerosis: (An update

    Directory of Open Access Journals (Sweden)

    Hossein Zarei

    2007-10-01

    Full Text Available BACKGROUND:To study the dimensions of fatigue in multiple sclerosis, its pathophysiology, the efficacy, tolerability and safety of drug and non-drug treatments and measurement of fatigue. METHODS: Relevant articles from PubMed and Google scholar search engines from January 1987 until September 2006 were studied to compose a short clinical update (not a systematic review and make the required clinical information available for the clinicians. RESULTS: There is evidence that fatigue is very common in all types and stages of multiple sclerosis, but its pathophysiology is not well explained. Consequently, few drug options have been offered for its treatment. Amantadine is the bestknown drug, though its efficacy and duration of action are limited. Pemoline and modafinil are alternatives and have
    some effects on fatigue. DAP (diaminopyridine, ASA (acetylsalicylic acid, methylphenidate and fluoxetine are other possible options but await further confirmation. Neurorehabilitation, regular exercise and cooling are confirmed to be of value in MS treatment. Measurement of fatigue is a complicated issue. At present fatigue does not have a laboratory marker. CONCLUSIONS: The results of this short clinical update provide guidelines for diagnosing MS-related fatigue and differentiating
    it from other similar physical and psychological conditions. It also examines prescription drug options and other therapies for MS patients with fatigue.
    KEYWORDS: Multiple sclerosis, fatigue, pathophysiology, treatment, measurement.

  15. Inverse comorbidity in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Koch-Henriksen, Nils; Laursen, Bjarne

    2016-01-01

    onset of MS 1980-2005. We randomly matched each MS-case with five population controls. Comorbidity data were obtained from multiple, independent nationwide registries. Cases and controls were followed from January 1977 to the index date, and from the index date through December 2012. We controlled...

  16. [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

  17. Grey matter pathology in multiple sclerosis.

    Science.gov (United States)

    Vercellino, Marco; Plano, Federica; Votta, Barbara; Mutani, Roberto; Giordana, Maria Teresa; Cavalla, Paola

    2005-12-01

    The aim of our study is to evaluate the extent and distribution of grey matter demyelinating lesions in multiple sclerosis (MS), addressing also neuronal loss and synaptic loss. Whole coronal sections of 6 MS brains and 6 control brains were selected. Immunohistochemistry was performed for myelin basic protein, neurofilaments, synaptophysin, ubiquitin, and activated caspase-3. Neuronal density and optical density of synaptophysin staining were estimated in cortical lesions and compared with those observed in corresponding areas of normal (i.e. nondemyelinated) cortex in the same section. Demyelinating lesions were observed in the cerebral cortex, in the thalamus, basal ganglia, and in the hippocampus. The percentage of demyelinated cortex was remarkable in 2 cases of secondary progressive MS (48% and 25.5%, respectively). Neuronal density was significantly reduced in cortical lesions (18-23% reduction), if compared with adjacent normal cortex, in the 2 cases showing the higher extent of cortical demyelination; in the same cases, very rare apoptotic neurons expressing caspase-3 were observed in cortical lesions and not in adjacent normal cortex. No significant decrease in optical density of synaptophysin staining was observed in cortical lesions. Grey matter demyelination and neuronal loss could contribute to disability and cognitive dysfunctions in MS.

  18. Mode of delivery in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Emanuele D’Amico

    2013-08-01

    Full Text Available Multiple sclerosis (MS is a chronic immune-mediated disorder of the central nervous system, affecting women of childbearing age. Little is known about the possible association between mode of delivery and the risk of MS in offspring. Delivery represents a unique event in a woman’s lifetime, with complex mechanisms controlling human parturition. Concurrent with the trend of increasing numbers of caesarean deliveries (CD, there has been an increasing frequency of autoimmune diseases such as MS. Several theories have emerged suggesting that environmental influences are contributing to this phenomenon. The data available in literature seem reassuring for women with MS, suggesting that the disease is not associated with adverse pregnancy or birth outcomes. On the other hand, there is little information in the literature regarding the role of mode of delivery in predicting the postpartum disease activity, pregnancy, and birth outcomes in women with MS. The aim of our review is to provide a brief summary of the available data on the role of mode of delivery in MS, and the eventual correlation with disease outcome.

  19. Chemokine Receptors as Biomarkers in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert J. Fox

    2006-01-01

    Full Text Available Leukocyte infiltrates characterize tissue inflammation and are thought to be integral in the pathogenesis of multiple sclerosis (MS. This attribute underlines the importance of understanding mechanisms of leukocyte migration. Chemokines are secreted proteins which govern leukocyte trafficking into targeted organs. Chemokine receptors (CKR are differentially expressed on leukocytes and their modulation is a potential target for MS disease modifying therapies. Chemokines and their receptors are also potential biomarkers of both disease activity and response to treatment. We describe the fluctuations in CKR expression on peripheral leukocytes in a group of MS patients followed longitudinally for up to 36 months. We observed little fluctuation in CKR expression within each patient over time, despite considerable variability in CKR expression between patients. These observations suggest that individual patients have a CKR set point, and this set point varies from one patient to another. Evaluation of chemokines or chemokine receptors as biomarkers in MS will need to account for this individual variability in CKR expression.

  20. Seizure characteristics in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Vahid Shaygannejad

    2013-01-01

    Full Text Available Background: To evaluate seizure characteristic among multiple sclerosis patients with coexistent seizure activity compared to control group. Materials and Methods : This study is a cross-sectional study which was conducted by reviewing the clinical records of patients with definite diagnosis of MS according to McDonald′s criteria from March 2007 to June 2011, who referred to the MS clinic of the university. Results : A total of 920 patients with a diagnosis of MS were identified, among whom 29 patients (3.15% with seizure activity (case due to MS with the mean age of 32.6 ± 6.23 years were analyzed. Also, fifty MS patients without any seizure occurrence with the mean age of 33.7 ± 7.4 years were used as our control group. In case group, seizure was general tonic clonic in 23 patients (79.3%, complex partial in four (13.8%, and simple partial in two (5.9%. The 26 available interictal EEGs in MS patients showed abnormal EEG pattern in 22 (84.6% of them, including focal epileptic form discharge or focal slowing in 10 (38.5%, generalized discharge (spike-wave, polyspike, or general paroxysmal fast activity in 10 (38.5%, and general slowing activity in 10 record (38.5%. MRI reviews of the 26 available brain MRIs showed subcortical white mater lesions in 22 (84.6% of patients with seizure. All MRIs were performed within one month after the first seizure episode. Amongst 48 available MRIs in our control group, 91.7% (44 cases showed periventricular lesions and in 8.3% (4 cases subcortical white matter lesions were reported. Conclusion : The result of this study demonstrated the higher rate of subcortical whit matter lesion in MS patients with seizure occurrence compared to control group.

  1. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging.

    Science.gov (United States)

    Ciccarelli, Olga; Barkhof, Frederik; Bodini, Benedetta; De Stefano, Nicola; Golay, Xavier; Nicolay, Klaas; Pelletier, Daniel; Pouwels, Petra J W; Smith, Seth A; Wheeler-Kingshott, Claudia A M; Stankoff, Bruno; Yousry, Tarek; Miller, David H

    2014-08-01

    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.

  2. Genes and Environment in Multiple Sclerosis project: A platform to investigate multiple sclerosis risk.

    Science.gov (United States)

    Xia, Zongqi; White, Charles C; Owen, Emily K; Von Korff, Alina; Clarkson, Sarah R; McCabe, Cristin A; Cimpean, Maria; Winn, Phoebe A; Hoesing, Ashley; Steele, Sonya U; Cortese, Irene C M; Chitnis, Tanuja; Weiner, Howard L; Reich, Daniel S; Chibnik, Lori B; De Jager, Philip L

    2016-02-01

    The Genes and Environment in Multiple Sclerosis project establishes a platform to investigate the events leading to multiple sclerosis (MS) in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects.

  3. Esclerosis múltiple: alteraciones cognitivas y actividades de la vida diaria = Multiple sclerosis : cognitive impairments and activities of daily living

    Directory of Open Access Journals (Sweden)

    Alegre Ayala, Jorge

    2008-02-01

    Full Text Available RESUMENLas alteraciones cognitivas ocasionadas por la Esclerosis Múltiple (EM dificultan el desempeño ocupacional de estos pacientes. No existe un patrón específico de deterioro cognitivo aunque son comunes las afectaciones de la memoria, los procesos atencionales, la velocidad de procesamiento de la información, las funciones ejecutivas, la fluidez verbal y la capacidad visuoespacial. Pese a no ser tan conocidos como los problemas físicos, los déficit cognitivos provocan limitaciones en la capacidad de estas personas para realizar sus actividades de la vida diaria (AVD. El artículo muestra explicaciones sobre las principales alteraciones cognitivas de la enfermedad y ejemplos de actividades de la vida diaria dañadas por éstas. SUMMARY Cognitive impairments caused by Multiple Sclerosis make these patients´ occupational performance difficult. It is not exist a specific pattern of cognitive injury although they are usual the affections in memory, attention process, speed of information processing, executive functions, verbal fluency and visual and spatial skills. Though are not so known like physical problems, the cognitive deficits provokes limitations in the ability of these persons to realize their activities of daily living. Article shows explains about principal cognitive impairments and examples of damage in the activities of daily living caused by Multiple Sclerosis.

  4. Acute Optic Neuritis: Prognosis for the Development of Multiple Sclerosis.

    Science.gov (United States)

    1979-12-01

    The literature was reviewed in regard to acute optic neuritis : prognosis for the development of multiple sclerosis, with specific reference to our...development of multiple sclerosis in patients affected with acute optic neuritis . This finding leads us to conclude that an incidence of 13% to 17...calculated on life tables) most accurately represents the risk that our flyers who are afflicted with optic neuritis will later develop multiple sclerosis. (Author)

  5. The management of multiple sclerosis in children: a European view

    DEFF Research Database (Denmark)

    Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey;

    2010-01-01

    in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce...... in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field....

  6. Research progress of MRI for cognitive impairment in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Xiao-fei ZHANG

    2016-04-01

    Full Text Available Multiple sclerosis (MS is a common inflammatory demyelinating disease that affects the central nervous system (CNS. It may be accompanied by cognitive impairment, however, the mechanism for cognitive impairment in multiple sclerosis is still unknown. More and more MRI techniques are used to improve the understanding on pathogenetic mechanism of cognitive impairment in multiple sclerosis. This paper summarizes MRI measures currently available to explain the possible mechanism for cognitive impairment of multiple sclerosis. DOI: 10.3969/j.issn.1672-6731.2016.04.012

  7. Rehabilitation interventions in multiple sclerosis: an overview.

    Science.gov (United States)

    Beer, Serafin; Khan, Fary; Kesselring, Jürg

    2012-09-01

    Multiple sclerosis is a complex, heterogeneous disease associated with long-term disability. Despite the availability of advanced disease-modifying and symptomatic therapies that may decrease activity and progression of disease and alleviate complaints to a certain extent, there is still a need for comprehensive rehabilitation interventions in order to reduce sequels and symptoms of the disease on personal activities and social participation to achieve the highest possible independence and the best quality of life. Timing and setting of rehabilitation interventions should be selected individually depending on disease phase, functional deficits, personal requirements, as well as specific goals. In addition, limitations and disease-specific characteristics that may influence rehabilitation outcome should be noted. Rehabilitation interventions should be considered early for maintaining functional capacity and reducing risk for losing important abilities or independence. Due to gradual failure of adaptive compensatory mechanisms along the course of disease, benefits of rehabilitation interventions are generally higher in earlier phases of MS. Inpatient and outpatient multidisciplinary rehabilitation has been shown to be beneficial in improving disability, participation and quality of life despite progression of the disease. Good evidence exists for different specific interventions improving physical and cognitive performance. Other important issues responsible for beneficial effects of comprehensive rehabilitation in MS include education, instruction, and information of patients and caregivers. Comprehensive assessment of health domains in MS patients using standardized framework and common language for describing the impact of disease at different levels, using International Classification of Functioning, Disability and Health (ICF) core sets may increase the knowledge of needs of these patients for more efficient and adapted rehabilitation interventions meeting these

  8. Cluster headache-like pain in multiple sclerosis.

    Science.gov (United States)

    Leandri, M; Cruccu, G; Gottlieb, A

    1999-10-01

    We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.

  9. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

    2013-01-01

    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH...... from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor(+)CD4(+)T-cells, was significantly......, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings from pathology studies which, along with the correlation between activated TFH- and B-cells and disease progression, suggest...

  10. [Pegylation and interferons in multiple sclerosis

    OpenAIRE

    Diego Centonze; Elisa Puma; Cecilia Saleri; Giulia Vestri; Sergio Iannazzo; Laura Santoni; Luigi Giuliani; Pier Luigi Canonico

    2016-01-01

    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...

  11. Emerging oral therapies for multiple sclerosis.

    Science.gov (United States)

    Miller, Colleen E; Umhauer, Margaret A

    2011-02-01

    Despite notable advances in the understanding of multiple sclerosis (MS) and the availability of several treatment options, there is a need for therapies that are more effective, safe, convenient, and well tolerated. Several new oral MS therapies are being investigated. Because data on these new therapies continue to emerge, nurses will play a pivotal role in educating patients regarding the benefits and risks of potential treatments and in monitoring patients for response, safety, tolerability, and adherence. This article reviews the oral MS therapies recently approved as well as those currently in development or submitted for Food and Drug Administration approval.

  12. Pregnancy in multiple sclerosis: a questionnaire study.

    Directory of Open Access Journals (Sweden)

    Nadja Borisow

    Full Text Available BACKGROUND: Multiple sclerosis (MS preferentially affects females at childbearing age. For this reason patients and treating physicians were frequently confronted with questions concerning family planning, pregnancy and birth. OBJECTIVE: The aim of this study was to evaluate the expertise about pregnancy related topics in multiple sclerosis of neurologists in private practice. METHODS: We developed a survey with 16 multiple choice questions about pregnancy related topics and sent it to neurologists in private practice in Berlin, Germany. RESULTS: 56 completed questionnaires were sent back. 54% of all questions were answered correctly, 21% of the questions were answered with "I don't know". Correct answers were more often given by physicians who treat more than 400 MS patients per year (p = 0.001. Further positive associations were found for assumed relevance of the topic (p = 0.002 and the degree of counseling (p<0.001. CONCLUSION: To provide a comprehensive counseling, MS patients with desire for children should be counseled by physicians with a lot of experience in MS treatment.

  13. Multiple sclerosis:New insights and trends

    Institute of Scientific and Technical Information of China (English)

    Khaled Mohamed Mohamed Koriem

    2016-01-01

    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 pro-gressive and progressive relapsing. Nine treatments have been accepted for relapsing-remitting MS type: interferon b-1a, interferon b-1b, mitoxantrone, natalizumab, glatir-amer 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.

  14. Multiple sclerosis: New insights and trends

    Institute of Scientific and Technical Information of China (English)

    Khaled Mohamed Mohamed Koriem

    2016-01-01

    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 immuneinflammatory, 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 relapsingremitting MS type: interferon b-1a, interferon b-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.

  15. Sphingolipids: Important Players in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Ramona Halmer

    2014-06-01

    Full Text Available Multiple Sclerosis (MS is the most common cause for permanent disability in young adults. Current pathophysiological understanding has identified an autoaggressive immune reaction with infiltration of immune cells into the central nervous system and local inflammatory and demyelinating reactions. The current therapy focuses on a modulation or suppression of immune functions. Sphingolipids, main components of nervous tissue, have been linked to MS already 60 years ago with the description of an unusual myelin lipid distribution in diseased patients. There is tremendous information developing on the role of different sphingolipids in MS. Antibodies against sphingomyelin, sulfatide or galacosylceramide have been detected in serum or CSF of MS patients, although up to now, this knowledge did not find its way into clinical use. Ceramide and the enzymes linked to its production have been described to play a pivotal role in oligendrocyte damage and demyelination. Nowadays, especially sphingosine-1-phosphate (S1P is in the focus of pathophysiological research and therapy development. A S1P analogue, FTY720, is a widely distributed therapy against relapsing-remitting MS, attenuating the emigration of activated, autoreactive lymphocytes from lymph nodes, thereby preventing new inflammatory infiltration into the central nervous system. Beside, there is more and more evidence, that especially S1P receptors on oligodendrocytes and astrocytes are involved in demyelination processes and subsequent axonal degeneration, important features of chonic progressive MS disease course. Further information and research on the manifold role of sphingolipids are needed to prepare the ground for further clinical trials. This review focuses on the current knowledge of the role of sphingolipids in MS and describes the current therapeutical implications.

  16. 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.

  17. Identifying responders and nonresponders to interferon therapy in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Prosperini L

    2014-04-01

    Full Text Available Luca Prosperini,1 Marco Capobianco,2 Costanza Giannì31Department of Neurology and Psychiatry, Sapienza University, Rome, Italy; 2Regional Multiple Sclerosis Centre, University Hospital San Luigi Gonzaga, Orbassano, Italy; 3Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USAAbstract: Interferon beta is a well established disease-modifying agent used for relapsing-remitting multiple sclerosis. Despite treatment, a relevant proportion of patients continue to experience clinical (ie, relapses, worsening of disability and magnetic resonance imaging (MRI activity. Early identification of responders and nonresponders to interferon beta is strongly recommended to select patients who need a prompt switch to another disease-modifying agent and to ultimately avoid accumulation of fixed disability over time. Detecting responders and nonresponders to interferon beta can be challenging, mainly because of the lack of a clear and shared clinical definition of response to treatment. Clinical features at the start of treatment should be considered as prognostic factors, but MRI parameters assessed during treatment, such as contrast-enhancing lesions or new T2-hyperintense lesions, may be sensitive markers of response to interferon beta. Quantitative scoring systems derived from a combination of relapses and MRI activity have recently been proposed as practical tools for use in the everyday clinical setting. Blood biomarkers, such as neutralizing antibodies to interferon beta and Myxovirus resistance protein A, provide further useful information for detecting responders and nonresponders to interferon beta. However, since the presence of neutralizing antibodies can only partially explain the nonresponse to interferon beta, biomarkers of interferon beta activity possibly related to the pathogenesis of the disease could represent a future step toward a tailored, long-lasting effective treatment against multiple sclerosis

  18. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    Science.gov (United States)

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  19. Dermatoglyphic features in patients with multiple sclerosis

    Science.gov (United States)

    Sabanciogullari, Vedat; Cevik, Seyda; Karacan, Kezban; Bolayir, Ertugrul; Cimen, Mehmet

    2014-01-01

    Objective: To examine dermatoglyphic features to clarify implicated genetic predisposition in the etiology of multiple sclerosis (MS). Methods: The study was conducted between January and December 2013 in the Departments of Anatomy, and Neurology, Cumhuriyet University School of Medicine, Sivas, Turkey. The dermatoglyphic data of 61 patients, and a control group consisting of 62 healthy adults obtained with a digital scanner were transferred to a computer environment. The ImageJ program was used, and atd, dat, adt angles, a-b ridge count, sample types of all fingers, and ridge counts were calculated. Results: In both hands of the patients with MS, the a-b ridge count and ridge counts in all fingers increased, and the differences in these values were statistically significant. There was also a statistically significant increase in the dat angle in both hands of the MS patients. On the contrary, there was no statistically significant difference between the groups in terms of dermal ridge samples, and the most frequent sample in both groups was the ulnar loop. Conclusions: Aberrations in the distribution of dermatoglyphic samples support the genetic predisposition in MS etiology. Multiple sclerosis susceptible individuals may be determined by analyzing dermatoglyphic samples. PMID:25274586

  20. Oroal manifestations in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Grajales González Hilda María

    2014-07-01

    Full Text Available Multiple sclerosis is a chronic autoimmune inflammatory disease of the central nervous system, characterized by the presence of acute focal inflammatory demyelination, axonal loss and gliosis. It affects predominantly in young adults between 20 and 40 years of age; it is infrequent in the pediatric age. A observational, retrospective and descriptive cohort research was conducted between May 1999 and January 2012 to assess demographic characteristics, and pathological manifestations in the oral cav- ity of children with this condition. Records of 17 patients, under 18 years of age, of either sex were included, who had been evaluated in the Department of Stomatology. Data recorded were age, sex, State of origin, oral and facial pathological features, focal cavity infections and ceod index. There were no patients with trigeminal neuralgia or facial paralysis; a 5.7% ceod index was identified. Most of the patients were under immunopressive treatment. A protocol for stomatological follow-up in patients with multiple sclerosis does not exist. The medical profession must be sensibilized to establish strategies for an integral follow-up in patients with this condition.

  1. Correlations Between Serum Uric Acid Level and Disease Activity, Intrathecal Inflammation Reactivity in Patients with Multiple Sclerosis

    Institute of Scientific and Technical Information of China (English)

    Cai-yan Liu; Yan Xu; Li-ying Cui; Bin Peng; Li-zhen Zhong; Xing-wang Chen; Jian-ming Wang

    2012-01-01

    Objective To explore the correlations between serum uric acid (UA) levels and the clinical and cerebrospinal fluid (CSF) parameters of multiple sclerosis (MS).Methods The medical reports of 47 MS patients admitted to Peking Union Medical College Hospital during 2008 and 2010 were reviewed.And 49 age- and gender-matched cerebral infarction patients were enrolled as control.The mean serum UA level of the MS patients was compared with that of the control group.The correlations betveen the UA levels and the clinical parameters including gender,disease duration,relapse rate,and disease disabilities as assessed by the Expanded Disability Status Scale score,were explored.Forty-one patients had CSF examinations.The correlations between the UA levels and the CSF parameters reflecting inflammation and tissue damage,including CSF protein,white blood cell count,oligoclonal band,24-hour IgG index,and myelin basic protein,were also investigated.Results The mean serum UA level in the MS patients was lower than that in the control group (247.75 ± 52.59 μmol/L vs.277.94 ± 74.33 μmol/L,P=0.025) and inversely correlated with the relapse rate (P=0.049).MS patients with lower serum UA levels tended to have higher white blood cell counts and myelin basic protein level.But there was no correlation between CSF protein levels (r=0.165,P=0.273),white blood cell counts (r=0.051,P=0.732),IgG index (r =0.045,P=0.802),or myelin basic protein level (r =0.248,P=0.145) and the serum UA level,respectively.Conclusion In MS patients,UA levels might partly reflect the extent of disability and inflammation.

  2. Changes in Blood B Cell-Activating Factor (BAFF Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Karin Kannel

    Full Text Available Multiple sclerosis (MS is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical

  3. MRI criteria for the diagnosis of multiple sclerosis

    DEFF Research Database (Denmark)

    Filippi, Massimo; Rocca, Maria A; Ciccarelli, Olga

    2016-01-01

    In patients presenting with a clinically isolated syndrome, MRI can support and substitute clinical information in the diagnosis of multiple sclerosis by showing disease dissemination in space and time and by helping to exclude disorders that can mimic multiple sclerosis. MRI criteria were first ...

  4. The natural history of primary progressive multiple sclerosis

    NARCIS (Netherlands)

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

    2009-01-01

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

  5. Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

    Science.gov (United States)

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

    2009-01-01

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

  6. Incidence of multiple sclerosis in Denmark 1948-1982

    DEFF Research Database (Denmark)

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

    1992-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-09-01

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

  8. The management of multiple sclerosis in children : a European view

    NARCIS (Netherlands)

    Ghezzi, Angelo; Banwell, Brenda; Boyko, Alexey; Amato, Maria Pia; Anlar, Banu; Blinkenberg, Morten; Boon, Maartje; Filippi, Massimo; Jozwiak, Sergiusz; Ketelslegers, Immy; Kornek, Barbara; Lim, Ming; Lindstrom, Eva; Nadj, Congor; Neuteboom, Rinze; Rocca, Maria A.; Rostasy, Kevin; Tardieu, Marc; Wassmer, Evangeline; Catsman-Berrevoets, Coriene; Hintzen, Rogier

    2010-01-01

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

  9. New oral disease-modifying therapies for multiple sclerosis

    OpenAIRE

    2009-01-01

    Several promising, oral disease-modifying therapies for multiple sclerosis are currently being evaluated in clinical trials. The arrival of effective oral agents for multiple sclerosis will be a major advance in the global effort to alter the natural history of this chronic disease.

  10. MicroRNA Dysregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Omar ede Faria Jr.

    2013-01-01

    Full Text Available Multiple Sclerosis (MS is a chronic inflammatory disease characterized by central nervous system (CNS demyelination and axonal degeneration. Although the cause of MS is still unknown, it is widely accepted that novel drug targets need to focus on both decreasing inflammation and promoting CNS repair. In MS and experimental autoimmune encephalomyelitis (EAE non-coding small microRNAs (miRNAs are dysregulated in the immune and central nervous systems. Since individual miRNAs are able to downregulate multiple targeted mRNA transcripts, even minor changes in miRNA expression may lead to significant alterations in post-transcriptional gene expression. Herein, we review miRNA signatures reported in CNS tissue and immune cells of MS patients and consider how altered miRNA expression may influence MS pathology.

  11. A typical MR imaging of multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Katagiri, Shinako; Kan, Shinichi; Ikeda, Toshiaki; Nishiyama, Syougo; Nishimaki, Hiroshi; Matsubayashi, Takashi; Hata, Takashi [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine

    1995-06-01

    MR imaging is very useful in detecting the intracranial lesion of multiple sclerosis (MS). We present six patients of MS with atypical MR imaging findings. Six patients aged 27-56 years (mean 36 years), and sexuality of six patients were 2 men and 4 females. Three patient`s clinical course had episodes of optic neuritis. The plaque`s size of the predominant lesion of the patients ranged from 3.0 to 9.0 cm in diameter. The plaques were oval, elliptically and other shaped. At acute stage, MR imaging detected perfocal edema and focal mass effect in three cases of our study. Two out of six cases showed multiple irregularly enhancing lesion with Gadolinium-DTPA. Plaques of all cases did not disappear completely in final MR imaging study. (author).

  12. Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis

    NARCIS (Netherlands)

    Huizinga, Ruth; van der Star, Baukje J.; Kipp, Markus; Jong, Rosa; Gerritsen, Wouter; Clarner, Tim; Puentes, Fabiola; Dijkstra, Christine D.; van der Valk, Paul; Amor, Sandra

    2012-01-01

    Neuroaxonal degeneration is a pathological hallmark of multiple sclerosis (MS) contributing to irreversible neurological disability. Pathological mechanisms leading to axonal damage include autoimmunity to neuronal antigens. In actively demyelinating lesions, myelin is phagocytosed by microglia and

  13. Dopamine, T cells and multiple sclerosis (MS).

    Science.gov (United States)

    Levite, Mia; Marino, Franca; Cosentino, Marco

    2017-03-10

    Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

  14. Orally active 7-substituted (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitriles as active-site inhibitors of sphingosine 1-phosphate lyase for the treatment of multiple sclerosis.

    Science.gov (United States)

    Weiler, Sven; Braendlin, Nadine; Beerli, Christian; Bergsdorf, Christian; Schubart, Anna; Srinivas, Honnappa; Oberhauser, Berndt; Billich, Andreas

    2014-06-26

    Sphingosine 1-phosphate (S1P) lyase has recently been implicated as a therapeutic target for the treatment of multiple sclerosis (MS), based on studies in a genetic mouse model. Potent active site directed inhibitors of the enzyme are not known so far. Here we describe the discovery of (4-benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile 5 in a high-throughput screen using a biochemical assay, and its further optimization. This class of compounds was found to inhibit catalytic activity of S1PL by binding to the active site of the enzyme, as seen in the cocrystal structure of derivative 31 with the homodimeric human S1P lyase. 31 induces profound reduction of peripheral T cell numbers after oral dosage and confers pronounced protection in a rat model of multiple sclerosis. In conclusion, this novel class of direct S1P lyase inhibitors provides excellent tools to further explore the therapeutic potential of T cell-targeted therapies in multiple sclerosis and other autoimmune and inflammatory diseases.

  15. Leg Spasticity and Ambulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Swathi Balantrapu

    2014-01-01

    Full Text Available Background. Spasticity of the legs is common in multiple sclerosis (MS, but there has been limited research examining its association with ambulatory outcomes. Objective. This study examined spasticity of the legs and its association with multiple measures of ambulation in persons with MS. Methods. The sample included 84 patients with MS. Spasticity of the legs was measured using a 5-point rating scale ranging between 0 (normal and 4 (contracted. Patients completed the 6-minute walk (6 MW, timed 25 foot walk (T25FW, and timed up-and-go (TUG, and O2 cost of walking was measured during the 6 MW. The patients undertook two walking trials on a GAITRite (CIR systems, Inc. for measuring spatial and temporal parameters of gait. The patients completed the Multiple Sclerosis Walking Scale-12 (MSWS-12 and wore an accelerometer over a seven-day period. Results. 52% (n=44 of the sample presented with spasticity of the legs. Those with leg spasticity had significantly worse ambulation as measured by 6 MW (P=0.0001, d=-0.86, T25FW (P=0.003,d=0.72, TUG (P=0.001, d=0.84, MSWS-12 (P=0.0001,d=1.09, O2 cost of walking (P=0.001, d=0.75, average steps/day (P<0.05, d=-0.45, and walking velocity (P<0.05, d=-0.53 and cadence (P<0.05, d=-0.46. Conclusion. Leg spasticity was associated with impairments in ambulation, including alterations in spatiotemporal parameters and free-living walking.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatme...

  17. Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis.

    Science.gov (United States)

    Choi, Sung R; Howell, Owain W; Carassiti, Daniele; Magliozzi, Roberta; Gveric, Djordje; Muraro, Paolo A; Nicholas, Richard; Roncaroli, Federico; Reynolds, Richard

    2012-10-01

    The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple sclerosis. Inflammation in the leptomeninges has been identified as a key feature of secondary progressive multiple sclerosis and may contribute to the extensive cortical pathology that accompanies progressive disease. Our aim was to investigate the extent of perivascular and meningeal inflammation in primary progressive multiple sclerosis in order to understand their contribution to the pathogenetic mechanisms associated with cortical pathology. A comprehensive immunohistochemical analysis was performed on post-mortem brain tissue from 26 cases with primary progressive multiple sclerosis. A variable extent of meningeal immune cell infiltration was detected and more extensive demyelination and neurite loss in the cortical grey matter was found in cases exhibiting an increased level of meningeal inflammation. However, no tertiary lymphoid-like structures were found. Profound microglial activation and reduction in neuronal density was observed in both the lesions and normal appearing grey matter compared with control cortex. Furthermore, cases with primary progressive multiple sclerosis with extensive meningeal immune cell infiltration exhibited a more severe clinical course, including a shorter disease duration and younger age at death. Our data suggest that generalized diffuse meningeal inflammation and the associated inflammatory milieu in the subarachnoid compartment plays a role in the pathogenesis of cortical grey matter lesions and an increased rate of clinical progression in primary progressive multiple sclerosis.

  18. Promising treatments of tomorrow for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Harrison Daniel

    2009-01-01

    Full Text Available The therapeutic options for multiple sclerosis are rapidly expanding. What was once seen as a disease with little hope for treatment is now a target of rapid drug development. Current therapies have demonstrated efficacy in limiting the impact of the disease, but none is fully effective in all patients. However, promising new treatments are on the horizon. In this review we will discuss potential novel immunomodulating drugs that are in advanced stages of investigation; these drugs include monoclonal antibodies, chimeric molecules, and oral therapies. The use of hematopoietic stem cells will also be discussed and, in addition, we will look farther ahead at possible novel targets for the development of new immunomodulatory or neuroprotective pharmaceuticals.

  19. Benefits of Exercise Training in Multiple Sclerosis.

    Science.gov (United States)

    Motl, Robert W; Sandroff, Brian M

    2015-09-01

    Exercise training represents a behavioral approach for safely managing many of the functional, symptomatic, and quality of life consequences of multiple sclerosis (MS). This topical review paper summarizes evidence from literature reviews and meta-analyses, supplemented by recent individual studies, indicating that exercise training can yield small but important improvements in walking, balance, cognition, fatigue, depression, and quality of life in MS. The paper highlights limitations of research on exercise training and its consequences and future research directions and provides an overview for promotion of exercise training in MS based on recent prescriptive guidelines. Collectively, the evidence for the benefits of exercise training in MS suggests that the time is ripe for the promotion of exercise by healthcare providers, particularly neurologists as a central part of the clinical care and management of MS patients.

  20. Dual diagnosis: rheumatoid arthritis and multiple sclerosis.

    Science.gov (United States)

    Ozsahin, Mustafa; Dikici, Suber; Kocaman, Gülsen; Besir, Fahri Halit; Baltaci, Davut; Ataoglu, Safinaz

    2014-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common rheumatologic disease in children. Moreover, multiple sclerosis (MS) is the most frequent demyelinating disease and has been associated with various chronic inflammatory diseases. However, its association with JRA has not been frequently described. Autoimmunity in both JRA and MS has been documented in the scientific literature, although there has been no definitive finding that patients with JRA are prone to the development of MS. An increasing frequency of MS resulting from an increased use of antitumor necrosis factor agents in the treatment of rheumatoid arthritis and other chronic inflammatory diseases has been reported recently. In this study, we report on the development of MS in a patient with JRA who did not have a history of antitumor necrosis factor use.

  1. The association between multiple sclerosis and uveitis

    DEFF Research Database (Denmark)

    Olsen, Tine Gadegaard; Frederiksen, Jette

    2016-01-01

    The association between multiple sclerosis (MS) and uveitis has been questioned. Nerve tissue and eye tissue develop from the same embryonic cells; thus, MS and uveitis could be etiologically associated. In published studies, the prevalence of MS in patients with uveitis differe from 0.7% to 30.......4%, whereas the prevalence of uveitis in patients with MS differe from 0.65% to 36.7%. Based on the largest retrospective studies, the prevalence of uveitis among MS patients is ∼1%, and the prevalence of MS among patients with uveitis is ∼1%. This is considerably higher than in the general population; thus......, more research on this topic is needed to further understand the relationship between MS and uveitis....

  2. [Multiple sclerosis: pathogenesis and manifestations in children].

    Science.gov (United States)

    Brissaud, O; Palin, K; Chateil, J F; Pedespan, J M

    2001-09-01

    Multiple sclerosis (MS) is rare in children and occurs exceptionally before ten years. Sex ratio (girl/boy) is around 2.5 to 3, higher than in adults. Brain stem dysfunction and meningeal symptoms are more commonly first manifestations of the disease than in adults. Optic neuritis is also a frequent early manifestation. The etiology of the disease remains unclear and none of the advanced hypotheses (infectious, genetic, environmental) can by themselves explain its occurrence. There is a genetic susceptibility which is probably linked to many genes leading to a low related risk (less than two). A viral trigger mechanism in a person with a genetic predisposition is possible. New therapies result from a better understanding of the closed immune mechanisms of the disease.

  3. Chemokines and Chemokine Receptors in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Wenjing Cheng

    2014-01-01

    Full Text Available Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

  4. Multiple sclerosis genetics: leaving no stone unturned.

    Science.gov (United States)

    Oksenberg, J R; Barcellos, L F

    2005-08-01

    Compelling epidemiologic and molecular data indicate that genes play a primary role in determining who is at risk for developing multiple sclerosis (MS), how the disease progresses, and how someone responds to therapy. The genetic component of MS etiology is believed to result from the action of allelic variants in several genes. Their incomplete penetrance and moderate individual effect probably reflects epistatic interactions, post-transcriptional regulatory mechanisms, and significant environmental influences. Equally significant, it is also likely that locus heterogeneity exists, whereby specific genes influence susceptibility and pathogenesis in some individuals but not in others. With the aid of novel analytical algorithms, the combined study of genomic, transcriptional, proteomic, and phenotypic information in well-controlled study groups will define a useful conceptual model of pathogenesis and a framework for understanding the mechanisms of action of existing therapies for this disorder, as well as the rationale for novel curative strategies.

  5. Neuropsychology in Multiple Sclerosis: A literature review.

    Directory of Open Access Journals (Sweden)

    Rodneys Mauricio Jiménez Morales

    2011-11-01

    Full Text Available Multiple sclerosis is an inflammatory disease of the central nervous system that is characterized by demyelination and degeneration. The objective of this article is to offer a review of the latest scientific discoveries in the field of neuropsychology in ME. A description is presented of the most frequent neuropsychological manifestations and their probable association with other factors such as: school level, fatigue, disability, cerebral dysfunction, time and clinical form of evolution, as well as depression and other states of mind starting from recent evidences in the scientific community. Also addressed is the development of tests and valid sensitive neuropsychological sets to evaluate cognitive functions. The use of sensitive and specific test facilitates the evaluation of neuropsychological alterations associated to ME, besides other socio-demographic and clinical-evaluative factors to contemplate in the exploration.

  6. Multiple sclerosis in India: An overview

    Directory of Open Access Journals (Sweden)

    Bhim S Singhal

    2015-01-01

    Full Text Available Multiple sclerosis (MS is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI. The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica - a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost.

  7. Disease-modifying agents in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Coyle P

    2009-01-01

    Full Text Available Since 1993, six disease-modifying therapies for multiple sclerosis (MS have been proven to be of benefit in rigorous phase III clinical trials. Other agents are also available and are used to treat MS, but definitive data on their efficacy is lacking. Currently, disease-modifying therapy is used for relapsing forms of MS. This includes clinically isolated syndrome/first-attack high-risk patients, relapsing patients, secondary progressive patients who are still experiencing relapses, and progressive relapsing patients. The choice of agent depends upon drug factors (including affordability, availability, convenience, efficacy, and side effects, disease factors (including clinical and neuroimaging prognostic indicators, and patient factors (including comorbidities, lifestyle, and personal preference. This review will discuss the disease-modifying agents used currently in MS, as well as available alternative agents.

  8. Total lymphoid irradiation for multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

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

  9. Insulin-like growth factor binding proteins: regulation in chronic active plaques in multiple sclerosis and functional analysis of glial cells

    NARCIS (Netherlands)

    Chesik, D.; De Keyser, J.; Glazenburg, L.; Wilczak, N.

    2006-01-01

    Studies in experimental allergic encephalomyelitis, an animal model of multiple sclerosis (MS), suggest that astrocyte-secreted insulin-like growth factor binding protein-2 (IGFBP-2) helps target IGF-1 to IGF-1 receptor-expressing oligodendrocytes and promote remyelination. We examined the presence

  10. Insulin-like growth factor binding proteins : regulation in chronic active plaques in multiple sclerosis and functional analysis of glial cells

    NARCIS (Netherlands)

    Chesik, Daniel; De Keyser, Jacques; Glazenburg, Lisa; Wilczak, Nadine

    2006-01-01

    Studies in experimental allergic encephalomyelitis, an animal model of multiple sclerosis (MS), suggest that astrocyte-secreted insulin-like growth factor binding protein-2 (IGFBP-2) helps target IGF-1 to IGF-1 receptor-expressing oligodendrocytes and promote remyelination. We examined the presence

  11. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2008-01-01

    Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and...

  12. BAYESIAN NETWORKS FOR SUB-GROUPS OF MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Yeliz KARACA

    2013-01-01

    Full Text Available In this study, patients with multiple sclerosis "sub-groups" characteristics in relation to detection of a statistically (SPSS and are provided in the Bayesian network. The main objective of this study, regarding the appearance of MRI lesions in patients with Multiple Sclerosis information and / or EDSS scores to investigate the possible attack of multiple sclerosis subgroups. Bayesian networks, reflects the level of sub-groups in multiple sclerosis patients. Analyzes were conducted to determine the change of these properties. MR images of the input data is discussed for the MS patients, the sub-groups of MS, "Remitting Relapsing Multiple Sclerosis", "Secondary Progressive Multiple Sclerosis" with their patients' clinical brain MR images, brain stem, and the Upper Cervical Regions of the corpus callosum-periventricular lesions created in the information. Multiple Sclerosis is owned by the input data is created correctly identify disease subgroups of MS patients for the number of lesions in MR images and MR image of the three regions for the year for which the information used in the EDSS score. Of MS is RRMS, SPMS correctly identify sub-groups of the brain with Brain Stem, and upper cervical regions of the corpus callosum-periventricular lesions in these three points for the region and / or EDSS score information can be emphasized by using the Bayesian networks play an important role in the analysis.

  13. Ipsilateral Uveitis and Optic Neuritis in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Eric Thouvenot

    2012-01-01

    Full Text Available Background. Uveitis is 20 times more frequent in multiple sclerosis (MS patients than in the general population. Methods. A retrospective study of local multiple sclerosis (n=700 and uveitis cohorts (n=450 described the ophthalmological and neurological characteristics of patients with multiple sclerosis and uveitis. Results. Uveitis and multiple sclerosis were associated in seven patients. The time intervals between diagnoses of MS and uveitis ranged from 6 months to 15 years. Analysis of the patients’ characteristics revealed that multiple sclerosis was associated with an older age of onset than usually expected, that is, 39 years. Uveitis was bilateral in three cases and mainly posterior (5/10. Five patients presented with acute optic neuritis (two in one eye and three in both eyes. All eyes presenting with acute optic neuritis were also affected by uveitis (P=0.02, though not simultaneously. Conclusion. The ipsilateral association between optic neuritis and uveitis in this series of patients with multiple sclerosis may suggest a reciprocal potentiation between optic neuritis and uveitis in multiple sclerosis.

  14. Antioxidant use as dietary therapy in patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Laura González-González

    2015-01-01

    Full Text Available INTRODUCTION Multiple sclerosis is an immune-mediated disease that produces chronic inflammation and neural degeneration. The disease progresses with acute attacks that result in myelin inflammation. This in turn increases oxidative stress and favors the appearance of reactive oxygen species. Reactive oxygen species damage neural cells causing apoptosis. The etiology of multiple sclerosis remains unknown and current therapy is aggressive and expensive. Recently, complementary and alternative medicine therapies have been proposed to control pathogenesis and symptoms of this disease. It is believed that these therapies help slow the progression of multiple sclerosis and improve survival. METHODS We conducted a MEDLINE/PubMed search using the following MeSH terms: diet, multiple sclerosis, antioxidants. We selected the main articles containing multiple sclerosis and diet. RESULTS We analyzed three case control studies that evaluated different dietary approaches in multiple sclerosis. For this review, we also included five experimental studies that studied the efficacy of lipoic acid in humans and rodents in diseases like multiple sclerosis, experimental autoimmune encephalomyelitis, and breast cancer.

  15. Amyotrophic lateral sclerosis: one or multiple causes?

    Directory of Open Access Journals (Sweden)

    Aline Furtado Bastos

    2011-04-01

    Full Text Available The Amyotrophic lateral sclerosis (ALS is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1, certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

  16. Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS Patients during Treatment with Natalizumab

    Directory of Open Access Journals (Sweden)

    Roberta Antonia Diotti

    2016-05-01

    Full Text Available The association between natalizumab and progressive multifocal leukoencephalopathy (PML is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24, when progressive multifocal leukoencephalopathy (PML risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039, not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239. This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097, a further decrease of the neutralizing activity was observed (p = 0.0062. This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment.

  17. Divergent Trends of Anti-JCPyV Serum Reactivity and Neutralizing Activity in Multiple Sclerosis (MS) Patients during Treatment with Natalizumab

    Science.gov (United States)

    Diotti, Roberta Antonia; Capra, Ruggero; Moiola, Lucia; Caputo, Valeria; De Rossi, Nicola; Sangalli, Francesca; Martinelli, Vittorio; Burioni, Roberto; Clementi, Massimo; Mancini, Nicasio

    2016-01-01

    The association between natalizumab and progressive multifocal leukoencephalopathy (PML) is established, but a reliable clinical risk stratification flow-chart is lacking. New risk factors are needed, such as the possible role of the anti-JC polyomavirus (JCPyV) neutralizing antibody. In this pilot study, we analyzed this parameter during natalizumab treatment. Sequential sera of 38 multiple sclerosis patients during their first year of natalizumab treatment were collected, and grouped according to the number of infusions. For 11 patients, samples were also available after 24 infusions (T24), when progressive multifocal leukoencephalopathy (PML) risk is higher. The reactivity against VP1, the main JCPyV surface protein, and the anti-JCPyV neutralizing activity were evaluated. During the first year, a lack of correlation between anti-JCPyV antibody response and its neutralizing activity was observed: a significant decrease in anti-JCPyV antibody response was observed (p = 0.0039), not paralleled by a similar trend in the total anti-JCPyV neutralizing activity (p = 0.2239). This lack of correlation was even more evident at T24 when, notwithstanding a significant increase in the anti-JCPyV response (p = 0.0097), a further decrease of the neutralizing activity was observed (p = 0.0062). This is the first study evidencing, prospectively, the lack of correlation between the anti-JCPyV antibody response and its neutralizing activity during natalizumab treatment. PMID:27164128

  18. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    Science.gov (United States)

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2014-05-01

    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; pholes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression.

  19. Dynamic Response Genes in CD4+ T Cells Reveal a Network of Interactive Proteins that Classifies Disease Activity in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Sandra Hellberg

    2016-09-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the CNS and has a varying disease course as well as variable response to treatment. Biomarkers may therefore aid personalized treatment. We tested whether in vitro activation of MS patient-derived CD4+ T cells could reveal potential biomarkers. The dynamic gene expression response to activation was dysregulated in patient-derived CD4+ T cells. By integrating our findings with genome-wide association studies, we constructed a highly connected MS gene module, disclosing cell activation and chemotaxis as central components. Changes in several module genes were associated with differences in protein levels, which were measurable in cerebrospinal fluid and were used to classify patients from control individuals. In addition, these measurements could predict disease activity after 2 years and distinguish low and high responders to treatment in two additional, independent cohorts. While further validation is needed in larger cohorts prior to clinical implementation, we have uncovered a set of potentially promising biomarkers.

  20. The symptomatic management of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Schapiro Randall

    2009-01-01

    Full Text Available The management of multiple sclerosis (MS revolves around disease management, symptom management, and person management. Of these, symptom management takes up the bulk of the time of the practicing physician. Some symptoms are easily managed whereas others are more difficult. Decisions have often to be made on whether to treat or to wait and watch. This article discusses the varied symptoms of MS and the approaches to management, which involves rehabilitation, pharmacological treatments, and surgical procedures. The skilled physician managing MS should be familiar with the multiple approaches to improving the quality of life of those with MS. After the diagnosis has been established and the decisions regarding treatment approaches have been made, the talk in a typical office appointment for MS usually turns to symptom management. Thus, the majority of management decisions made by the clinician revolve around that important topic. It is symptom management that will determine quality of life for those with MS, It is the basis for improving function, and, up until twenty years ago, it was the only basis for treating MS. Now, however, we can approach treatment by disease management, symptom management, and person management. The MS specialist must be well versed in all three areas.

  1. Mimicry between mitochondrial disorder and multiple sclerosis.

    Science.gov (United States)

    Finsterer, Josef; Höftberger, Romana; Stöllberger, Claudia; Rolinski, Boris

    2012-06-01

    Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non-enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs.

  2. Bone Health in Patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Vit Zikan

    2011-01-01

    Full Text Available Multiple sclerosis (MS is a gait disorder characterized by acute episodes of neurological defects leading to progressive disability. Patients with MS have multiple risk factors for osteoporotic fractures, such as progressive immobilization, long-term glucocorticoids (GCs treatment or vitamin D deficiency. The duration of motor disability appears to be a major contributor to the reduction of bone strength. The long term immobilization causes a marked imbalance between bone formation and resorption with depressed bone formation and a marked disruption of mechanosensory network of tightly connected osteocytes due to increase of osteocyte apoptosis. Patients with higher level of disability have also higher risk of falls that combined with a bone loss increases the frequency of bone fractures. There are currently no recommendations how to best prevent and treat osteoporosis in patients with MS. However, devastating effect of immobilization on the skeleton in patients with MS underscores the importance of adequate mechanical stimuli for maintaining the bone structure and its mechanical competence. The physical as well as pharmacological interventions which can counteract the bone remodeling imbalance, particularly osteocyte apoptosis, will be promising for prevention and treatment of osteoporosis in patients with MS.

  3. Multiple sclerosis and positive lyme serology

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-02-15

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

  6. Hydroxycitric acid ameliorates inlfammation and oxidative stress in mouse models of multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Mahdi Goudarzvand; Shahin Khadem Azarian; Abbas Mirshaifey; Gholamreza Azizi; Sanaz Afraei; Somaye Yaslianifard; Saleh Ghiasy; Ghazal Sadri; Mustafa Kalvandi; Tina Alinia; Ali Mohebbi; Reza Yazdani

    2016-01-01

    Hydroxycitric acid (HCA) is derived primarily from the Garcinia plant and is widely used for its anti-in-lfammatory effects. Multiple sclerosis can cause an inlfammatory demyelination and axonal damage. In this study, to validate the hypothesis that HCA exhibits therapeutic effects on multiple sclerosis, we established female C57BL/6 mouse models of multiple sclerosis,i.e., experimental autoimmune encephalomyelitis, using Complete Freund’s Adjuvant (CFA) emulsion containing myelin oligodendrocyte glycoprotein (35–55). Treatment with HCA at 2 g/kg/d for 3 weeks obviously improved the symptoms of nerve injury of experimental autoimmune encephalomyelitis mice, decreased serum interleulin-6, tumor necrosis factor alpha, nitric oxide, and malondialdehyde levels, and increased superoxide dismutase and glutathione reduc-tase activities. hTese ifndings suggest that HCA exhibits neuroprotective effects on multiple sclerosis-caused nerve injury through ameliorating inlfammation and oxidative stress.

  7. Direct and indirect economic consequences of multiple sclerosis in Ireland

    LENUS (Irish Health Repository)

    Fogarty, Emer

    2014-09-01

    Multiple sclerosis (MS) has significant financial consequences for healthcare systems, individual patients and households, and the wider society. This study examines the distribution of MS costs and resource utilisation across cost categories and from various perspectives, as MS disability increases.

  8. Increased expression of distinct galectins in multiple sclerosis lesions

    NARCIS (Netherlands)

    Stancic, M.; van Horssen, J.; Thijssen, V. L.; Gabius, H. -J.; van der Valk, P.; Hoekstra, D.; Baron, W.

    2011-01-01

    Aims: Multiple sclerosis (MS) is a chronic progressive degenerative disorder of the central nervous system, characterized by inflammation, demyelination, ultimate failure of remyelination and axonal loss. Current research identifies galectins, adhesion/growth-regulatory effectors binding beta-galact

  9. Cognitive analysis of multiple sclerosis utilizing fuzzy cluster means

    Directory of Open Access Journals (Sweden)

    Imianvan Anthony Agboizebeta

    2012-01-01

    Full Text Available Multiple sclerosis, often called MS, is a disease that affects the central nervous system (the brain and spinal cord. Myelin provides insulation for nerve cells improves the conduction of impulses along the nerves and is important for maintaining the health of the nerves. In multiple sclerosis, inflammation causes the myelin to disappear. Genetic factors, environmental issues and viral infection may also play a role in developing the disease. Ms is characterized by life threatening symptoms such as; loss of balance, hearing problem and depression. The application of Fuzzy Cluster Means (FCM or Fuzzy CMean analysis to the diagnosis of different forms of multiple sclerosis is the focal point of this paper. Application of cluster analysis involves a sequence of methodological and analytical decision steps that enhances the quality and meaning of the clusters produced. Uncertainties associated with analysis of multiple sclerosis test data are eliminated by the system

  10. Cognitive analysis of multiple sclerosis utilizing fuzzy cluster means

    Directory of Open Access Journals (Sweden)

    Imianvan Anthony Agboizebeta

    2012-02-01

    Full Text Available Multiple sclerosis, often called MS, is a disease that affects the central nervous system (the brain andspinal cord. Myelin provides insulation for nerve cells improves the conduction of impulses along thenerves and is important for maintaining the health of the nerves. In multiple sclerosis, inflammationcauses the myelin to disappear. Genetic factors, environmental issues and viral infection may alsoplay a role in developing the disease. Ms is characterized by life threatening symptoms such as; loss ofbalance, hearing problem and depression. The application of Fuzzy Cluster Means (FCM or Fuzzy CMeananalysis to the diagnosis of different forms of multiple sclerosis is the focal point of this paper.Application of cluster analysis involves a sequence of methodological and analytical decision stepsthat enhances the quality and meaning of the clusters produced. Uncertainties associated withanalysis of multiple sclerosis test data are eliminated by the system

  11. The effect of exercise therapy on fatigue in multiple sclerosis

    DEFF Research Database (Denmark)

    Andreasen, A; Stenager, E; Dalgas, U

    2011-01-01

    Fatigue occurs in the majority of patients with multiple sclerosis (MS) and therapeutic possibilities are few. Exercise therapy is a therapeutic option but no studies have systematically reviewed the existing literature evaluating the effect of exercise therapy on MS fatigue....

  12. Profile of the Brazilian scientific production in multiple sclerosis

    OpenAIRE

    Araujo C.R.; Moreira M.A.; Lana-Peixoto M.A.

    2006-01-01

    This paper analyzes the profile of the Brazilian output in the field of multiple sclerosis from 1981 to 2004. The search was conducted through the MEDLINE and LILACS databases, selecting papers in which the term "multiple sclerosis" was defined as the main topic and "Brazil" or "Brasil" as others. The data were analyzed regarding the themes, the state in Brazil and institution where the papers were produced, the journals where the papers were published, journal's impact factor, and language. ...

  13. The Ocular Manifestations of Drugs Used to Treat Multiple Sclerosis.

    Science.gov (United States)

    Heath, Gregory; Airody, Archana; Gale, Richard Peter

    2017-03-01

    Recent times have seen an increase in the number of options to treat multiple sclerosis. Ocular manifestations of multiple sclerosis are well known to treating physicians; however, the medications used to treat multiple sclerosis can also have ocular side effects. This review article focuses on the ocular manifestations of corticosteroids and disease-modifying agents such as interferon, fingolomod, natalizumab, alemtuzumab and mitoxantron used to treat the disease. The ocular manifestations of multiple sclerosis treatments can be varied depending on the drug used, and include retinopathy, chronic central serous chorioretinopathy, macular oedema, Graves' ophthalmopathy and cortical blindness. These effects may be specific to the drug or secondary to their immunosuppressive effect. The association of macular oedema with fingolomod is clear and merits ocular screening for toxicity. The immunosuppressive nature of the treatments makes patients prone to acquired infections. Hence, if a patient with multiple sclerosis presents with vision loss, infectious and drug-induced aetiology should be considered alongside relapses of multiple sclerosis itself as a cause.

  14. Connective tissue diseases mimicking multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Maryam Moghaddassi-Jahromi

    2011-11-01

    Full Text Available Background: Connective tissue diseases (CTD can involve nervous system. Diagnosis and differentiation from multiple sclerosis (MS can be difficult especially when the disease presented by symptoms and signs related to demyelinating process. The aim of this article is to review the variant forms of central nervous system involvement in CTD especially useful points for differentiation from demyelinating disorders. Materials and Method: We used the relevant articles in PUBMED, Scopus and other databases especially published in recent ten years. Results: Systemic lupus erythematosus (SLE, antiphospholipid syndrome (APS, Behcet’s disease (BD, Sjogren's syndrome (SS, and some vasculitides can involve nervous system. Patients may be present by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from MS and other demyelinating processes, such as transverse myelitis and optic neuritis. On the other hand, autoantibodies such as antinuclear antibodies (ANA and antiphospholipid antibodies (aPL can also occur in MS. Treatment and prognosis of these diseases are quite different. In demyelinating diseases the diagnosis is established on the basis of clinical presentation, magnetic resonance imaging (MRI, cerebrospinal fluid (CSF examination, visual evoked potentials (VEP and autoantibody investigation.Conclusion: In many patients, distinction between different etiologies of demyelination can be made by considering clinical and paraclinical data, but in some cases, accurate diagnosis can only be made after long-term follow-up

  15. Symptom overlap in anxiety and multiple sclerosis.

    LENUS (Irish Health Repository)

    O Donnchadha, Seán

    2013-02-14

    BACKGROUND: The validity of self-rated anxiety inventories in people with multiple sclerosis (pwMS) is unclear. However, the appropriateness of self-reported depression scales has been widely examined. Given somatic symptom overlap between depression and MS, research emphasises caution when using such scales. OBJECTIVE: This study evaluates symptom overlap between anxiety and MS in a group of 33 individuals with MS, using the Beck Anxiety Inventory (BAI). METHODS: Participants underwent a neurological examination and completed the BAI. RESULTS: A novel procedure using hierarchical cluster analysis revealed three distinct symptom clusters. Cluster one (\\'wobbliness\\' and \\'unsteady\\') grouped separately from all other BAI items. These symptoms are well-recognised MS-related symptoms and we question whether their endorsement in pwMS can be considered to reflect anxiety. A modified 19-item BAI (mBAI) was created which excludes cluster one items. This removal reduced the number of MS participants considered \\'anxious\\' by 21.21% (low threshold) and altered the level of anxiety severity for a further 27.27%. CONCLUSION: Based on these data, it is suggested that, as with depression measures, researchers and clinicians should exercise caution when using brief screening measures for anxiety in pwMS.

  16. [Parenthood in aspect of multiple sclerosis].

    Science.gov (United States)

    Ciepiela, Lesław

    2010-01-01

    Multiple sclerosis is a central nervous system disease. It is mainly characterized by passing neurological disorders at first which alter into permanent symptoms. The most frequent are tiredness, sensation disturbance and limbs, face, body becoming numb. Pregnancy doubtfully influence MS, but the most important question is about treatment during pregnancy. Should we carry pregnancy during immunomodular treatment? But crucial aspect is if a newborn baby will be healthy. To make attempt into discussion about the subject of SM and pregnancy we should perform a test how many sick people get married and or if maternity and paternity influence a disease course. Our research may bring answers, why statistically less SM men become single and do not own children and if unmarried status is influenced by sexual disturbance. Our conclusion will be compared with already written facts. Patients were between 18-35 year old are the subject of research. The group consist of 24 patients, 9 men and 15 women. Final conclusion could bring the answer if definite willingness to have a baby should be recommended.

  17. [Epidemiology of multiple sclerosis in Tiumen' region].

    Science.gov (United States)

    Sivertseva, S A; Zhuravlev, M N; Murav'ev, S A; Boĭko, A N

    2006-01-01

    Prevalence of multiple sclerosis (MS) was evaluated in the pilot study of 731 patients living in Tyumen city and a southern part of Tyumen region as well as in Khanty-Mansi (KMAO) and Yamal-Nenets (YNAO) autonomic okrugs. An index of MS prevalence was 22,4 per 100,000 in Tyumen region as a whole. This index was higher--29.1 per 100 000 - in the southern part. In KMAO and YNAO, the MS prevalence was 14,3 and 27,8 respectively. Women prevailed among patients in all the regions, their number being twice higher (461 and 270). However, if in the southern part and in KMAO this ratio was approximately equal, in YNAO percentage of men was significantly higher. It should be noted that these data need further study. We revealed that using of current diagnostic criteria may often lead to misunderstanding of diagnosis of "definite" MS. Essential difference in MS prevalence in different regions may be explained by ethnical stratification. In particular, there are many newly migrated people in the okrugs and MS occurs more often in that group. At the same time, there is no any information on the prevalence of "definite" MS among the native-born population of KMAO and YNAO.

  18. Depression in multiple sclerosis: a review.

    Science.gov (United States)

    Siegert, R J; Abernethy, D A

    2005-04-01

    Several studies have reported high rates of depression in multiple sclerosis (MS) with a lifetime prevalence of approximately 50% and an annual prevalence of 20% not uncommon. Concern about the potential of new drug treatments to exacerbate or precipitate depression in MS has led to increased interest in the relation between MS and depression. This review on MS and depression identifies the following key issues: How common is depression in people with MS? Is depression in MS associated with lesions in specific regions of the central nervous system? Is there an increased risk of suicide in MS? Is there a higher than expected incidence of anxiety disorders in MS? Are fatigue and depressed mood related in MS? Is there a relation between depression and cognitive impairment in MS? Which psychosocial variables affect the development of depression in MS? Does treatment with interferon increase the risk of depression? How effective are treatments for MS patients with depression? Each of these issues is briefly reviewed with critical commentary, and some priorities for future research are suggested.

  19. B Cells and Autoantibodies in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Anne-Katrin Pröbstel

    2015-07-01

    Full Text Available While over the past decades T cells have been considered key players in the pathogenesis of multiple sclerosis (MS, it has only recently become evident that B cells have a major contributing role. Our understanding of the role of B cells has evolved substantially following the clinical success of B cell-targeting therapies and increasing experimental evidence for significant B cell involvement. Rather than mere antibody-producing cells, it is becoming clear that they are team players with the capacity to prime and regulate T cells, and function both as pro- and anti-inflammatory mediators. However, despite tremendous efforts, the target antigen(s of B cells in MS have yet to be identified. The first part of this review summarizes the clinical evidence and results from animal studies pointing to the relevance of B cells in the pathogenesis of MS. The second part gives an overview of the currently known potential autoantigen targets. The third part recapitulates and critically appraises the currently available B cell-directed therapies.

  20. 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.

  1. Proton MR spectroscopic imaging in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Tedeschi, G.; Bonavita, S. [Istituto di Scienze Neurologiche, Seconda Universita di Napoli (Italy); Department of Neuroimaging, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, MD (United States); McFarland, H.F.; Richert, N. [Department of Neuroimmunology, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, MD (United States); Duyn, J.H.; Frank, J.A. [Laboratory of Diagnostic Radiology Research, National Institutes of Health, Bethesda, MD (United States)

    2002-01-01

    We studied 24 patients with multiple sclerosis (MS) by proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the neurochemical pathology of the white-matter lesions (WML) and normal-appearing white matter (NAWM). Our 1H-MRSI technique allowed simultaneous measurement of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm slices divided into 0.84 ml single-volume elements. In WML we found significantly lower NAA/Cr and NAA/Cho ratios and a significantly higher Cho/Cr ratio than in NAWM or control white matter. In NAWM, NAA/Cr and Cho/Cr were significantly lower than in control white matter. 1H-MRSI was compatible with damage to myelin in WML, and with axonal damage and/or dysfunction in WML and NAWM. These findings extend data on involvement of NAWM in MS beyond the abnormalities visible on MRI. (orig.)

  2. The Transition to Secondary Progressive Multiple Sclerosis

    Science.gov (United States)

    Wood, Fiona; Brain, Katherine E.; Edwards, Michelle; Jones, Rhiannon; Wallbank, Rachel; Robertson, Neil P.; Edwards, Adrian

    2016-01-01

    Background: Identifying the transition from relapsing-remitting to secondary progressive multiple sclerosis (SPMS) can be challenging for clinicians. Little previous research has explored how professionals experience working with patients during this specific stage of the disease. We explored the experiences of a group of multidisciplinary professionals who support patients in the transition to SPMS to describe this stage from a professional perspective. Methods: This qualitative semistructured interview study included 11 professionals (medical, nursing, and allied health professionals; specialists and generalists) working with patients with MS in South Wales, United Kingdom. Thematic analysis of the interview data was performed. Results: Two overarching themes were identified: the transition and providing support. The transition theme comprised issues related to recognizing and communicating about SPMS. Uncertainty influenced recognizing the transition and knowing how to discuss it with patients. The providing support theme included descriptions of challenging aspects of patient care, providing support for caregivers, using the multidisciplinary team, and working within service constraints. Providing adequate psychological support and engaging patients with self-management approaches were seen as particularly challenging. Conclusions: Caring for patients in the transition to SPMS generates specific challenges for professionals. Further research on health-care interactions and patients'/professionals' experiences regarding the transition phase may help identify strategies for professional development and learning and how to optimize the patient experience at this difficult stage of disease. PMID:27803641

  3. Therapeutic Yoga: Symptom Management for Multiple Sclerosis.

    Science.gov (United States)

    Rogers, Kim A; MacDonald, Megan

    2015-11-01

    Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system, affecting over 2.3 million people worldwide. According to the National Institute of Neurological Disorders and Stroke, the age of disease onset is typically between 20 and 40 years, with a higher incidence in women. Individuals with MS experience a wide range of symptoms, including declining physical, emotional, and psychological symptoms (e.g., fatigue, imbalance, spasticity, chronic pain, cognitive impairment, bladder and bowel dysfunction, visual and speech impairments, depression, sensory disturbance, and mobility impairment). To date, both the cause of and cure for MS remain unknown. In recent years, more individuals with MS have been pursuing alternative methods of treatment to manage symptoms of the disease, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. It has been suggested that the practice of yoga may be a safe and effective way of managing symptoms of MS. Therefore, the purpose of this paper is to summarize the most relevant literature on exercise and mind-body modalities to treat MS symptoms and, more specifically, the benefits and potential role of yoga as an alternative treatment of symptom management for individuals with MS. The article also discusses future directions for research.

  4. Multiple sclerosis care in Latin America.

    Science.gov (United States)

    Rivera, Victor M; Medina, Marco Tulio; Duron, Reyna M; Macias, Miguel Angel

    2014-05-01

    Before the advent of diagnostic criteria for multiple sclerosis (MS), it was reported that the prevalence of MS in Mexico was "one of the lowest in the world" (1.6/100,000).(1) The notion that MS was a rare neurologic disease among those living in the tropics of the Americas and Southern latitudes was widely accepted. The geopolitical boundaries of the region identified as Latin America (LA) extend from the southern border of United States with Mexico (32° North latitude) to the Argentinian and Chilean Patagonia in South America (56° South latitude). The largest Spanish-speaking island countries in the Caribbean-Cuba, Dominican Republic, and Puerto Rico-are also traditionally considered part of LA. The continental mass includes 17 countries with a population of more than 550 million. Due to centuries of racial intermixing, it is a heterogeneous and genetically complex population. The blended cultures of native Amerindians with white Caucasian Europeans and black Africans has resulted in the predominant ethnic Latin American Mestizo. The influence of African genetics is notable in many areas of the subcontinent and the Caribbean. A common observation across LA is the absence of identification of MS in non-mixed Amerindians(2); the reason for this phenomenon is unclear.

  5. A toolbox for multiple sclerosis lesion segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Roura, Eloy; Oliver, Arnau; Valverde, Sergi; Llado, Xavier [University of Girona, Computer Vision and Robotics Group, Girona (Spain); Cabezas, Mariano; Pareto, Deborah; Rovira, Alex [Vall d' Hebron University Hospital, Magnetic Resonance Unit, Dept. of Radiology, Barcelona (Spain); Vilanova, Joan C. [Girona Magnetic Resonance Center, Girona (Spain); Ramio-Torrenta, Lluis [Dr. Josep Trueta University Hospital, Institut d' Investigacio Biomedica de Girona, Multiple Sclerosis and Neuroimmunology Unit, Girona (Spain)

    2015-10-15

    Lesion segmentation plays an important role in the diagnosis and follow-up of multiple sclerosis (MS). This task is very time-consuming and subject to intra- and inter-rater variability. In this paper, we present a new tool for automated MS lesion segmentation using T1w and fluid-attenuated inversion recovery (FLAIR) images. Our approach is based on two main steps, initial brain tissue segmentation according to the gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) performed in T1w images, followed by a second step where the lesions are segmented as outliers to the normal apparent GM brain tissue on the FLAIR image. The tool has been validated using data from more than 100 MS patients acquired with different scanners and at different magnetic field strengths. Quantitative evaluation provided a better performance in terms of precision while maintaining similar results on sensitivity and Dice similarity measures compared with those of other approaches. Our tool is implemented as a publicly available SPM8/12 extension that can be used by both the medical and research communities. (orig.)

  6. The role of astrocytes in Multiple Sclerosis progression

    Directory of Open Access Journals (Sweden)

    Jorge eCorreale

    2015-08-01

    Full Text Available Multiple sclerosis is an inflammatory disorder causing central nervous system demyelination and axonal injury. Although its etiology remains elusive, several lines of evidence support the concept that autoimmunity plays a major role in disease pathogenesis.The course ofMS is highly variable; nevertheless, the majority of patients initially present a relapsing-remitting clinical course. After 10-15 years of disease, this pattern becomes progressive in up to 50% of untreated patients, during which time clinical symptoms slowly cause constant deterioration over a period of many years. In about 15% of MS patients however, disease progression is relentless from disease onset. Published evidence supports the concept that progressive multiple sclerosis reflects a poorly understood mechanism of insidious axonal degeneration and neuronal loss. Recently, the type of microglial cell and of astrocyte activation and proliferation observed has suggested contribution of resident central nervous system cells may play a critical role in disease progression. Astrocytes could contribute to this process through several mechanisms: a as part of the innate immune system, b as a source of cytotoxic factors, c inhibiting re-myelination and axonal regeneration by forming a glial scar, and d contributing to axonal mitochondrial dysfunction. Furthermore, regulatory mechanisms mediated by astrocytes can be affected by aging. Notably, astrocytes might also limit the detrimental effects of pro-inflammatory factors, while providing support and protection for oligodendrocytes and neurons. Because of the dichotomy observed in astrocytic effects, the design of therapeutic strategies targeting astrocytes becomes a challenging endeavor. Better knowledge of molecular and functional properties of astrocytes therefore, should promote understanding of their specific role in multiple sclerosis pathophysiology, and consequently lead to development of novel and more successful

  7. Targeting Epstein-Barr virus infection as an intervention against multiple sclerosis.

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    Jons, D; Sundström, P; Andersen, O

    2015-02-01

    We here review contemporary data on genetic and environmental risk factors, particularly Epstein-Barr virus infection, for multiple sclerosis. There is an important immunogenetic etiological factor for multiple sclerosis. However, a general assumption is that immune defense genes are activated by the environment, basically by infections. We contend that the relationship between infectious mononucleosis and multiple sclerosis cannot be completely explained by genetics and inverse causality. Epstein-Barr infection as indicated by positive serology is an obligatory precondition for multiple sclerosis, which is a stronger attribute than a risk factor only. Data on events in the early pathogenesis of multiple sclerosis are cumulating from bio-banks with presymptomatic specimens, but there is only little information from the critical age when Epstein-Barr infection including infectious mononucleosis is acquired, nor on the detailed immunological consequences of this infection in individuals with and without multiple sclerosis. We discuss how focused bio-banking may elaborate a rationale for the development of treatment or vaccination against Epstein-Barr virus infection. A cohort in which intervention against Epstein-Barr infections was performed should be the object of neurological follow-up.

  8. Dimethyl fumarate: a new oral treatment option for multiple sclerosis

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    Sarjana S. Atal

    2013-12-01

    Full Text Available Multiple Sclerosis (MS is a slowly progressive, immunologically mediated disease of the CNS. The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis. There is a clear need for more effective, safe and at the same time orally available treatment options. Here we review the recently approved drug Dimethyl fumarate (DMF, Tecfidera® as a new therapeutic option for MS and its role in context to the existing oral treatment options for MS. Dimethyl fumarate is the methyl ester of fumaric acid and has been claimed to possess immunomodulatory properties and is already in clinical use as Fumaderm for severe systemic psoriasis. In addition, Dimethyl fumarate was also shown to act on the blood-brain barrier and exert neuroprotective properties via activation of anti-oxidative pathways and displayed beneficial effects in experimental autoimmune encephalomyelitis (EAE, a model mimicking many aspects of MS. Based on two global phase III studies. Dimethyl fumarate has been clinically proven to significantly reduce important measures of disease activity, including relapses and development of brain lesions, as well as to slow disability progression over time, while demonstrating a favourable safety and tolerability profile. [Int J Basic Clin Pharmacol 2013; 2(6.000: 849-856

  9. [Mitoxantrone role in treatment of primary progressive multiple sclerosis].

    Science.gov (United States)

    Pastuszak, Żanna; Stępień, Adam; Tomczykiewicz, Kazimierz; Piusińska-Macoch, Renata; Durka-Kęsy, Marta

    2016-01-01

    Multiple sclerosis is a chronic, autoimmunological disease of central nervous system in which axonal damage in brain and spinal cord is observed. It is second most common cause of disability in young adults in West Europe and North America after injuries. There is 2.5 million people suffered from multiple sclerosis worldwide. The worse prognosis is connected with primary progressive MS in which recovery after first symptoms of central nervous system damage isn't observed. That subtype of disease is seen in case of 10-20% people with MS. MTX is a synthetic antracycline with antineoplastic, immunomodulatory and anti-inflammatory effects. Drug was allowed to treatment of leukemia. It is also used in treatment of breast, prostate, ovarian, stomach and liver cancer. Additionally MTX is used in treatment of secondary progressive SM and relapsing - remitting subtype of disease with no respond to treatment with interferon beta and glatiramer acetate. MTX inhibits topoisomerase II activity, matches to DNA molecule and damage her structure. Drug inhibits limphocyte T, B and macrophages activity and antibodies synthesis. The most dangerous side effects of MTX treatment are cardiotoxicity and induction of leukemia. There is lack of studies describing MTX effectiveness and safety in treatment of primary progressive SM.

  10. Development of Activity-Related Muscle Fatigue during Robot-Mediated Upper Limb Rehabilitation Training in Persons with Multiple Sclerosis: A Pilot Trial

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    Johanna Renny Octavia

    2015-01-01

    Full Text Available Robot-assisted rehabilitation facilitates high-intensity training of the impaired upper limb in neurological rehabilitation. It has been clinically observed that persons with Multiple Sclerosis (MS have difficulties in sustaining the training intensity during a session due to the development of activity-related muscle fatigue. An experimental observational pilot study was conducted to examine whether or not the muscle fatigue develops in MS patients during one session of robot-assisted training within a virtual learning environment. Six MS patients with upper limb impairment (motricity index ranging from 50 to 91/100 and six healthy persons completed five training bouts of three minutes each performing lifting tasks, while EMG signals of anterior deltoid and lower trapezius muscles were measured and their subjective perceptions on muscle fatigue were registered. Decreased performance and higher subjective fatigue perception were present in the MS group. Increased mean EMG amplitudes and subjective perception levels on muscle fatigue were observed in both groups. Muscle fatigue development during 15′ training has been demonstrated in the arm of MS patients, which influences the sustainability of training intensity in MS patients. To optimize the training performance, adaptivity based on the detection of MS patient’s muscle fatigue could be provided by means of training program adjustment.

  11. Serum antibodies to 25 myelin oligodendrocyte glycoprotein epitopes in multiple sclerosis and neuromyelitis optica: clinical value for diagnosis and disease activity

    Institute of Scientific and Technical Information of China (English)

    XU Yan; ZHANG Yao; LIU Cai-yan; PENG Bin; WANG Jian-ming; ZHANG Xiao-jun; LI Hai-feng; CUI Li-ying

    2012-01-01

    Background Whether antibody to myelin oligodendrocyte glycoprotein (MOG) can be a diagnostic marker for multiple sclerosis (MS) is still controversial.Recent studies suggested that serum specific anti-MOG epitope antibody might be an MS specific marker.However,these studies did not include neuromyelitis optica (NMO) which might be proven to also have anti-MOG antibody.Hence,the present study was undertaken to investigate the clinical value of serum antibodies to 25 MOG epitopes in conventional MS (CMS) and NMO.Methods Serum anti-MOG epitope IgG was detected in 61 CMS patients,54 NMO patients,and 77 healthy controls,using enzyme-linked immunosorbent assay (ELISA).Results Anti-MOG27-38 IgG levels in both CMS and NMO patients were significantly higher than that in healthy controls (optical density (OD):0.64±0.38,0.48±0.23 vs.0.19±0.09; P=0.000).CMS and NMO patients in relapse stage had significantly higher anti-MOG27-38 IgG level than patients in remission stage (OD:0.55±0.14 vs.0.24±0.09,P=0.027).Conclusion Although serum anti-MOG epitope IgG could not differentiate MS from NMO,it may be a useful marker for monitoring disease activity.

  12. Interferons and Natalizumab for Multiple Sclerosis

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    Busse, Reinhard

    2008-10-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system which is accompanied by considerable disability and high costs. This report summarises the evidence on effectiveness and costs of beta-interferons and natalizumab in the treatment of multiple sclerosis. The review included systematic reviews and randomised controlled trials (with an observation time of at least one year in patients with MS which assessed outcome parameters such as progression, exacerbations and adverse effects. An extensive literature search included databases such as MEDLINE, EMBASE, the Cochrane Library and various HTA-databases. Studies were selected according to predefined criteria, their quality was assessed according to criteria defined prospectively, and data were summarised systematically in tables. Cost-effectiveness evaluations were also included.Two systematic reviews and 24 randomised controlled trials of beta-interferon therapy were included, as well as three trials on the effectiveness of natalizumab. A total of 22 cost-effectiveness analyses for interferons were included, whereas no economic evaluations for natalizumab were identified. Use of interferon beta-1a or interferon beta-1b after a first demyelinating event led to a reduction of the conversion to definite MS during an observation time of two to three years. In relapsing remitting MS, interferon beta-1a reduced progression. The effects of interferon beta-1b on progression are unclear. Interferon beta-1a and interferon beta-1b reduced in some but not all studies outcomes relating to exacerbations. In direct comparison trials, interferon beta-1b (Betaferon® or Betaseron® and interferon beta-1a (Rebif®, higher dosage of 44 µg three subcutaneous injections per week proved superior to interferon beta-1a (Avonex®, 30 µg per week intramuscular with respect to exacerbation outcomes. For secondary progressive MS, only one of five studies found a reduced progression with

  13. Dietary Pattern and Risk of Multiple Sclerosis

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    Mahdi Aloosh

    2012-01-01

    Full Text Available Background:It has been suggested that nutrition might play a role in the etiology of multiple sclerosis (MS. However,dietary patterns associated with MS risk are unknown. This study was conducted to compare the dietary patterns of patients with MS and healthy controls to find the relationship between dietary patterns and MS.Methods:Usual dietary intake of 75 women with relapsing/remitting MS (RRMS and 75 healthy controls were assessed with a food frequency questionnaire consisting of 168 food items. To define major dietary patterns, we used factor analysis. Multivariate logistic regression was used to assess the relationship between dietary patterns and risk of MS.Results:Traditional pattern (high in low-fat dairy products,red meat, vegetable oil, onion, whole grain, soy, refined grains, organ meats, coffee, and legumes was inversely related to the risk of MS [odds ratio (OR = 0.15; 95%confidence interval (CI: 0.03-0.18; P = 0.028]. A similar inverse relationship was noted between MS risk andlacto-vegetarian (high in nuts, fruits, French fries, coffee,sweets and desserts, vegetables, and high-fat dairy products and vegetarian (high in green leafy vegetables, hydrogenated fats, tomato, yellow vegetables, fruit juices, onion, and other vegetablespatterns (OR = 0.31; 95% CI: 0.12-0.82; P = 0.018 and OR = 0.42; 95% CI: 0.19-0.90; P = 0.026, respectively. In contrast, the prevalence of MS was higher in those who had high animal fat dietary pattern (high in animal fats,potato, meat products, sugars, and hydrogenated fats and low in whole grains (OR = 1.99; 95% CI: 1.63-2.94;P < 0.005.Conclusion:Our findings showed that the risk of RRMS can be affected by major dietary patterns.

  14. Poor sleep in patients with multiple sclerosis.

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    Hanne Marie Bøe Lunde

    Full Text Available BACKGROUND: Poor sleep is a frequent symptom in patients with multiple sclerosis (MS. Sleep may be influenced by MS-related symptoms and adverse effects from immunotherapy and symptomatic medications. We aimed to study the prevalence of poor sleep and the influence of socio-demographic and clinical factors on sleep quality in MS- patients. METHODS: A total of 90 MS patients and 108 sex-and age- matched controls were included in a questionnaire survey. Sleep complaints were evaluated by Pittsburgh Sleep Quality Index (PSQI and a global PSQI score was used to separate good sleepers (≤ 5 from poor sleepers (>5. Excessive daytime sleepiness, the use of immunotherapy and antidepressant drugs, symptoms of pain, depression, fatigue and MS-specific health related quality of life were registered. Results were compared between patients and controls and between good and poor sleepers among MS patients. RESULTS: MS patients reported a higher mean global PSQI score than controls (8.6 vs. 6.3, p = 0.001, and 67.1% of the MS patients compared to 43.9% of the controls (p = 0.002 were poor sleepers. Pain (p = 0.02, fatigue (p = 0.001, depression (p = 0.01 and female gender (p = 0.04 were associated with sleep disturbance. Multivariate analyses showed that female gender (p = 0.02, use of immunotherapy (p = 005 and a high psychological burden of MS (p = 0.001 were associated with poor sleep among MS patients. CONCLUSIONS: Poor sleep is common in patients with MS. Early identification and treatment of modifiable risk factors may improve sleep and quality of life in MS.

  15. Prevalence of celiac disease in multiple sclerosis

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    López-Vázquez Antonio

    2011-03-01

    Full Text Available Abstract Background Celiac disease (CD is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS patients and their first-degree relatives. Methods We analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls. Results Tissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%, compared to 3 healthy controls (2.4% (p We detected mild or moderate villous atrophy (Marsh III type in duodenal biopsies, in 8 MS patients (11.1%. We also found a high proportion of CD among first-degree relatives: 23/126 (32%. Several associated diseases were detected, mainly dermatitis 41 (57% and iron deficiency anemia in 28 (39% MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%, ANA in 11 (15% and AMA in 2 (3%. Conclusions We have found an increased prevalence of CD in 8 of the 72 MS patients (11.1% and also in their first-degree relatives (23/126 [32%]. Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable.

  16. Anxiety in patients with multiple sclerosis.

    Science.gov (United States)

    Riether, A M

    1999-04-01

    Anxiety disorders are quite common, and frequently overlooked, in patients with Multiple Sclerosis (MS). This is often due to the difficulty differentiating anxiety from personality correlates or reactive tendencies in patients with neurologic disease. This chapter offers the consulting psychiatrist guidelines for providing psychological support to patients with MS at various stages of their disease. DSM-IV-based differential diagnosis, psychotherapeutic techniques, behavioral interventions, and pharmacological support (including the newer alternative therapies) are reviewed. The physical, functional, and symbolic losses caused by this chronic and progressive disease are considered in the broader context of individual patients' lives. Particular attention has been given to specific pharmacological treatment of steroid-induced anxiety. This is essential knowledge for the consulting psychiatrist. The overlap between depressive symptoms, manic symptoms and cognitive changes in MS patients is reviewed with special emphasis on the structural correlates. Current neuro-imaging techniques, including emerging technologies such as gadolinium enhancement, single photon emission computed tomography and brain electrical mapping (BEAM), now provide a far more accurate view of brain damage in MS. This permits diagnosis of the disease much earlier, and is also beginning to show correlation between neuropsychiatric clinical findings, and the nature and location of demyelinating plaques in the brains of MS patients. This chapter seeks to clearly define the associations between anxiety disorders and cerebral involvement in MS patients, suggesting that common neurological and biochemical mechanisms are more extensive than generally suspected. It is hoped that this information will aid clinicians in more accurately diagnosing and effectively treating anxiety in MS patients.

  17. Altered thalamic functional connectivity in multiple sclerosis

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    Liu, Yaou; Liang, Peipeng; Duan, Yunyun; Huang, Jing; Ren, Zhuoqiong; Jia, Xiuqin [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong, Huiqing; Ye, Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Shi, Fu-Dong [Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Butzkueven, Helmut [Department of Medicine, University of Melbourne, Parkville 3010 (Australia); Li, Kuncheng, E-mail: kunchengli55@gmail.com [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2015-04-15

    Highlights: •We demonstrated decreased connectivity between thalamus and cortical regions in MS. •Increased intra- and inter-thalamic connectivity was also observed in MS. •The increased functional connectivity is attenuated by increasing disease duration. -- Abstract: Objective: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. Methods: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. Results: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r = −0.59, p < 0.001). Conclusion: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is

  18. Perceived Behavioral Changes in Early Multiple Sclerosis

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    Fabiana Souza Lima

    2007-01-01

    Full Text Available Acquired behavioral changes have essentially been described in advanced multiple sclerosis (MS. The present study was designed to determine whether behavioral modifications specifically related to the MS pathological process could be identified in the initial phase of the disease, as compared to control patients with chronic, relapsing and progressive inflammatory disorders not involving the central nervous system (CNS. Eighty-eight early MS patients (Expanded Disability Status Scale score ≤ 2.5 and 48 controls were tested. Perceived changes by informants in behavioral control, goal-directed behavior, decision making, emotional expression, insight and interpersonal relationships were assessed using the Iowa Scale of Personality Change (ISPC. Executive behavioral disturbances were screened using the Dysexecutive Questionnaire (DEX. The mean change between the premorbid and postmorbid ISPC ratings was similar in the MS [12.2 (SD 15.6] and in the control [11.5 (SD 15.1] group. The perceived behavioral changes (PBCs most frequently reported in both groups were lack of stamina, lability/moodiness, anxiety, vulnerability to stress and irritability. Pathological scores in the DEX were also similar in both groups. Correlations between PBCs and DEX scores were different in MS and control groups. MS patients with cognitive impairment had a marginally higher number of PBCs than control patients (p = 0.056 and a significantly higher DEXp score (p = 0.04. These results suggest that (1 PBCs occurring in early MS patients were not different from those induced by comparable chronic non-CNS disorders, (2 qualitative differences in the relationship between behavioral symptoms and executive-behavioral changes may exist between MS and control groups, and (3 behavioral symptoms seem associated with cognitive deficits in MS. We further plan to assess these observations longitudinally.

  19. [Pathogenic mechanisms of neuronal damage in multiple sclerosis].

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    Flores-Alvarado, Luis Javier; Gabriel-Ortiz, Genaro; Pacheco-Mois, Fermín P; Bitzer-Quintero, K

    2015-06-01

    Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients' lives.

  20. Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

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    Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-02-01

    Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis.

  1. 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...... years of treatment (hazard ratio 2.04, 95% confidence interval 1.47-2.85).The gene variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or disease progression. CONCLUSIONS: Pretreatment relapse rate and clinical disease activity during the first 2 years of treatment may be associated...

  2. The assessment of problems in functioning and the subjective perception of these problems in people with Multiple Sclerosis : the Multiple Sclerosis Impact Profile (MSIP)

    NARCIS (Netherlands)

    Wynia, Klaske; Roodbol, Petrie F.; Middel, Berry

    2009-01-01

    People with Multiple Sclerosis (MS) perceive consequences of this chronic condition that are not limited to impairments in physical functioning but also have their impact on limitations in activities and restrictions in participation in life situations. There is a growing awareness among healthcare

  3. Application study of the components Activity and Participation of the ICF Checklist used in people with Multiple Sclerosis and its relation to the Core Sets

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    Rosé Colom Toldrá

    2016-10-01

    Full Text Available Introduction: The Core Set is a group of typical and significant functionality categories of the International Classification of Functioning, Disability and Health – ICF used for certain health conditions. Objective: The study reviewed the application of the component categories Activities and Participation based on the ICF Checklist for multiple sclerosis (MS and its relationship with the comprehensive and validated Core Sets by occupational therapists. Method: Descriptive quantitative research from collection and organization of data questionnaire based on the components Activities and Participation of the ICF Checklist - Version 2.1ª. Clinical form for the ICF containing 25 categories belonging to 6 domains and analysis of its relationship with the Core Sets. Participated 115 people with relapsing-remitting MS without disability to moderate disability, treated at the Central Institute of Hospital Clinics of the Faculty of Medicine University of São Paulo. We created database in Excel and made descriptive analysis of frequencies. Results: Most participants were women (85, mean age 32 years and 1 month (± 7.4. Study broadens the evidence of the applicability of the Comprehensive Core Set with 88% (22 and Core Set validated by occupational therapists with 72% (18 compared evaluated categories. More significant difficulties were encountered in the categories d640 Doing housework, d430 Lifting and carrying objects and d850 Remunerative employment, which reflected on the performance of various activities and social participation. Conclusion: Studies on application of the Core Set validated by occupational therapists are recommended to extend the evidence of professional clinical practice and inclusion of categories depending on the context.

  4. Cell-based reparative therapies for multiple sclerosis.

    Science.gov (United States)

    Ben-Hur, Tamir; Fainstein, Nina; Nishri, Yossi

    2013-11-01

    The strong rationale for cell-based therapy in multiple sclerosis is based on the ability of stem and precursor cells of neural and mesenchymal origin to attenuate neuroinflammation, to facilitate endogenous repair processes, and to participate directly in remyelination, if directed towards a myelin-forming fate. However, there are still major gaps in knowledge regarding induction of repair in chronic multiple sclerosis lesions, and whether transplanted cells can overcome the multiple environmental inhibitory factors which underlie the failure of endogenous repair. Major challenges in clinical translation include the determination of the optimal cellular platform, the route of cell delivery, and candidate patients for treatment.

  5. Vision and vision-related outcome measures in multiple sclerosis.

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    Balcer, Laura J; Miller, David H; Reingold, Stephen C; Cohen, Jeffrey A

    2015-01-01

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

  6. Symptomatic cranial neuralgias in multiple sclerosis: clinical features and treatment.

    Science.gov (United States)

    De Santi, Lorenzo; Annunziata, Pasquale

    2012-02-01

    In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of neuropathic pain. Neuralgias are characterised by paroxysmal painful attacks of electric shock-like sensation, occurring spontaneously or evoked by innocuous stimuli in specific trigger areas. In multiple sclerosis, demyelination in the centrally myelinated part of the cranial nerve roots plays an important role in the origin of neuralgic pain. These painful syndromes arising in multiple sclerosis are therefore considered "symptomatic", in contrast to classic cranial neuralgias, in which no cause other than a neurovascular contact is identified. At this time, the evidence on the management of symptomatic cranial neuralgias in multiple sclerosis is fragmentary and a comprehensive review addressing this topic is still lacking. For that reason, treatment is often based on personal clinical experience as well as on anecdotal reports. The aim of this review is to critically summarise the latest findings regarding the pathogenesis, the diagnosis, the instrumental evaluation and the medical as well as neurosurgical treatment of symptomatic trigeminal, glossopharyngeal and occipital neuralgia in multiple sclerosis, providing useful insights for neurologists and neurosurgeons and a broad range of specialists potentially involved in the treatment of these painful syndromes.

  7. Treatment of multiple sclerosis with the pregnancy hormone estriol.

    Science.gov (United States)

    Sicotte, Nancy L; Liva, Stephanie M; Klutch, Rochelle; Pfeiffer, Paul; Bouvier, Seth; Odesa, Sylvia; Wu, T C Jackson; Voskuhl, Rhonda R

    2002-10-01

    Multiple sclerosis patients who become pregnant experience a significant decrease in relapses that may be mediated by a shift in immune responses from T helper 1 to T helper 2. Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift. We treated nonpregnant female multiple sclerosis patients with the pregnancy hormone estriol in an attempt to recapitulate the beneficial effect of pregnancy. As compared with pretreatment baseline, relapsing remitting patients treated with oral estriol (8 mg/day) demonstrated significant decreases in delayed type hypersensitivity responses to tetanus, interferon-gamma levels in peripheral blood mononuclear cells, and gadolinium enhancing lesion numbers and volumes on monthly cerebral magnetic resonance images. When estriol treatment was stopped, enhancing lesions increased to pretreatment levels. When estriol treatment was reinstituted, enhancing lesions again were significantly decreased. Based on these results, a larger, placebo-controlled trial of estriol is warranted in women with relapsing remitting multiple sclerosis. This novel treatment strategy of using pregnancy doses of estriol in multiple sclerosis has relevance to other autoimmune diseases that also improve during pregnancy.

  8. Inflammatory Optic Neuritis: From Multiple Sclerosis to Neuromyelitis Optica.

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    de Seze, Jérôme

    2013-01-01

    Inflammatory optic neuritis represents a frequent clinical situation in neurology and ophthalmology. In those parts of the world where multiple sclerosis is common, it is the condition most discussed as the cause of optic neuritis. However, the risk for conversion from optic neuritis to multiple sclerosis is evaluated at only around 50% after 15 years of follow-up. The risk is higher in cases in whom abnormalities typical of multiple sclerosis are found on magnetic resonance imaging of the brain and oligoclonal bands found on cerebrospinal fluid protein electrophoresis with no corresponding bands in serum. When these investigations are normal, optic neuritis is usually considered as "idiopathic" with a suspected viral aetiology, but in some cases, a systemic disease such as sarcoidosis, systemic lupus erythematosis, or Sjögren syndrome may be diagnosed. In rare cases, either recurrent optic neuritis or myelitis may occur without any evidence for multiple sclerosis. In the first case, it corresponds to a recently characterised disorder referred to as chronic relapsing inflammatory optic neuropathy and in the second case to a recently better identified entity, neuromyelitis optica. In the present paper, the differential diagnosis of inflammatory optic neuritis is presented from multiple sclerosis to infectious optic neuritis, systemic disease, and neuromyelitis optica.

  9. Social conflict exacerbates an animal model of multiple sclerosis.

    Science.gov (United States)

    Meagher, Mary W; Johnson, Robin R; Vichaya, Elisabeth Good; Young, Erin E; Lunt, Shannon; Welsh, C Jane

    2007-07-01

    A growing body of evidence suggests that social conflict is associated with inflammatory disease onset and exacerbations in multiple sclerosis (MS) patients and in animal models of MS. This review illustrates how animal research can be used to elucidate the biobehavioral mechanisms underlying the adverse health effects of social conflict. The authors review studies indicating that social conflict exacerbates a virally initiated animal model of MS. This research suggests that the deleterious effects of social conflict may be partially mediated by stress-induced increases in pro-inflammatory cytokine levels in the central nervous system. In addition, they provide evidence that the adverse health effects of social conflict can be prevented by blocking the stress-induced increases in cytokine activity. This suggests that interventions designed to prevent or reverse the stress-induced increases in cytokine activity may be able to prevent or reverse some of the negative health effects of social conflict in humans.

  10. Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis.

    Science.gov (United States)

    Dhib-Jalbut, Suhayl

    2007-05-29

    Substantial evidence supports autoimmune activity as the etiologic mechanism underlying multiple sclerosis (MS). Both the innate and the adaptive arms of the immune system are involved in the aberrant response to several antigens associated with the myelin sheath and oligodendrocytes (OGCs) after the activation of immune cells by self- or cross-reactive microbial pathogens. The CD4(+) Th1 cell, in particular, has been implicated, but it is abetted by a variety of other cell types (CD8(+) cells, B cells, macrophages, and microglia) and soluble products (proteases, cytokines, and nitric oxide [NO]) that act both outside of and within the CNS. This review describes recent and salient findings from animal models and human clinical studies that have established our current understanding of the distinct steps in the development of immune autoreactivity that culminates in the CNS lesions associated with MS.

  11. Regulation of T Cell Activation and Differentiation by Extracellular Vesicles and Their Pathogenic Role in Systemic Lupus Erythematosus and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Cristina Ulivieri

    2017-02-01

    Full Text Available How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu. Moreover, depending on the specific microenvironment, self-reactive effector T cells have the ability to change their phenotype, especially Th17 and regulatory T (Treg cells, which are characterized by the highest instability. In this context, cell-derived extracellular vesicles, i.e., vesicles carrying cytosolic proteins and nucleic acids protected by a phospholipid bilayer, as well as membrane-associated proteins, with the ability to spread throughout the body by means of biological fluids, are emerging as key mediators in intercellular communications and in the modulation of the microenvironment. In this review, we will discuss recent findings implicating extracellular vesicles (EVs at different steps of CD4+ T cell differentiation to specific effectors, with a focus on the Th17/Treg balance and its alterations in systemic lupus erythematosus and multiple sclerosis.

  12. Association of celiac disease with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Abolfazli.R

    2007-09-01

    Full Text Available   Background: Multiple sclerosis (MS and the gluten intolerance disease, celiac disease, (CD are immune-mediated diseases. Better testing for antibodies associated with CD, including anti-gliadin antibody [AGA], as well as anti-endomysial and anti-tissue transglutaminase antibodies, has improved the diagnosis of CD. Certain neurologic conditions have a reported association with CD. Previous researchers have investigated the role of a gluten-free diet in the treatment of MS and found no benefits. Here, we investigate the possible immunological association of CD with MS.Methods: Using ELISA, we estimated serum IgG and IgA anti-gliadin and IgA anti-endomysial antibodies in 34 MS patients, who were new or previous cases without immunosuppressant treatment for at least the last six months. The mean age was 29.6 years (range 15-46 years, with 30 patients relapsing-remitting, and four secondary-progressive MS. Thirty-four random anonymous blood donors were used as serologic controls (mean age 31.4 years, range 19-50 years. The individuals in both groups with elevated AGA (IgG or IgA or anti-endomysial antibody (IgA underwent duodenal biopsy.Results: In the MS group, high levels of IgG AGA were found in 5.9% of the subjects, and 5.9% had elevated IgA AGA. In the controls, elevated IgG AGA was detected in 5.9% of the subjects and IgA AGA in 2.9% (p=0.051 and 0.48, respectively. For IgG and IgA AGA levels, no significant differences were found between the patient and control groups. IgA anti-endomysial antibodies were not found in either group. Upon biopsy, the specific pathological features of celiac were absent.Conclusion: The same number of MS patients and controls had high levels of AGA, with normal levels of IgA anti-endomysial antibodies, which is more specific for CD, while the GI biopsies from both groups were not specific for CD. Therefore, AGA levels in any neurologic case should be interpreted with caution. The present study showed no

  13. 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...

  14. Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

    Science.gov (United States)

    Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

    2017-01-01

    Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with

  15. Remyelination strategies in multiple sclerosis: a critical reflection.

    Science.gov (United States)

    Kipp, Markus

    2016-01-01

    Remyelination is the natural repair mechanism of demyelination and can be a highly efficient process in multiple sclerosis. However, in the majority of lesions, this regenerative approach is incomplete or fails. It is believed that remyelination protects against progressive axonal damage and thus long-term disability in patients with multiple sclerosis. For this reason, therapeutic promotion of remyelination represents an attractive option for preventing disease progression. In this editorial we casts a critical eye over the most frequently used experimental settings which aim to uncover potential remyelination promoting drugs. This article reflects upon the personal opinion of the author who currently used animal models allow to assess the potency of pharmacological interventions to accelerate, but not to induce myelin repair. Furthermore, it is discussed how remyelination and neuroprotection might well be two separate entities. Thus, induction of remyelination does not necessarily prevent disease progression in multiple sclerosis patients.

  16. [Multiple sclerosis associated with antiphospholipid syndrome: diagnostic and therapeutic difficulties].

    Science.gov (United States)

    Ahbeddou, N; Ait Ben Haddou, E; Hammi, S; Slimani, C; Regragui, W; Benomar, A; Yahyaoui, M

    2012-01-01

    Strokes are the main neurological manifestation of antiphospholipid syndrome. Other clinical presentations are possible and may mimic classic symptoms of multiple sclerosis (MS). A 46-year-old woman, with a history of two miscarriages, presented four subacute neurological episodes (optic neuritis, right facial paralysis, paraparesis of the thigh, and right brachial monoparesis). Using McDonald criteria, the diagnosis of multiple sclerosis was retained. Because of the occurrence of thrombocytopenia during a final relapse, we reconsidered the diagnosis of MS. Search for antiphospholipid antibodies was positive. All clinical manifestations and complementary tests were compatible with the diagnosis of antiphospholipid syndrome associated with multiple sclerosis. Given the great similarity of clinical, radiological and biological findings in the two diseases, non-thrombotic neurological manifestations of antiphospholipid syndrome can be difficult to distinguish from MS associated with antiphospholipid syndrome.

  17. Disease-modifying treatments for progressive multiple sclerosis.

    Science.gov (United States)

    Comi, Giancarlo

    2013-10-01

    The last 20 years have seen major progress in the treatment of relapsing-remitting multiple sclerosis (RRMS) using a variety of drugs targeting immune dysfunction. In contrast, all clinical trials of such agents in primary progressive multiple sclerosis (PPMS) have failed and there is limited evidence of their efficacy in secondary progressive disease. Evolving concepts of the complex interplay between inflammatory and neurodegenerative processes across the course of multiple sclerosis (MS) may explain this discrepancy. This paper will provide an up-to-date overview of the rationale and results of the published clinical trials that have sought to alter the trajectory of both primary and secondary MS, considering studies involving drugs with a primary immune target and also those aiming for neuroprotection. Future areas of study will be discussed, building on these results combined with the experience of treating RRMS and new concepts emerging from laboratory science and animal models.

  18. Multiple Sclerosis: two clinical presentations, a single disease!

    Directory of Open Access Journals (Sweden)

    Ana Margarida Ferreira da Silva

    2014-09-01

    Full Text Available Objective: this case report aims to demonstrate the diversity of clinical presentations, the symptoms evolution and the role of the primary care physician in the diagnosis and management of patients with multiple sclerosis, and their families. Case descriptions: two women, 31 and 28 years old, Caucasian, inserted within nuclear families (phases II and IV of the Duvall’ cycle, respectively belonging to the middle class of Graffar. The first one starts an insidious symptom of paraesthesia of the hands with improvement in 2 months. Within a year, she presents with difficulty raising the eyelids and marked imbalance. The second one presents sudden loss of visual acuity on the right, having been diagnosed with optic neuritis. Both were diagnosed with multiple sclerosis. Conclusion: multiple sclerosis is a chronic inflammatory, degenerative and demyelinating disease of the central nervous system that manifests heterogeneously. It is important for the family doctor to know how to deal with diagnostic uncertainties.

  19. Prevalence of multiple sclerosis in Denmark 1950-2005

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  20. A CASE STUDY OF BRAIN VOLUME REDUCTION IN MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    Ivan N. Dimitrov

    2013-07-01

    Full Text Available The development of sophisticated magnetic resonance imaging techniques and software for medical imaging processing and analysis has led to a significant progress in multiple sclerosis research and clinical care. The measurement of brain volumes provides a quantitative representation of damage, thus facilitating the objective follow-up process. The parameters obtained, though not being used routinely in clinical practice, are more and more often applied in clinical studies. The amount of whole brain and regional atrophy, estimated from serial scans, is considered important not only for disease progression, but also for cognitive dysfunction which is common in multiple sclerosis. In this paper we describe a volumetric study of two magnetic resonance scans of a patient with relapsing-remitting multiple sclerosis, performed 16 months one after the other, and analyzed using FSL SIENA software. Analysis demonstrated brain volume reduction of 1.7% between the two scans. We discuss the advantages of the method and its possible clinical applications.

  1. Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV

    DEFF Research Database (Denmark)

    Brudek, Tomasz; Luhdorf, P; Christensen, Tove;

    2007-01-01

    factors in HERV activation. We demonstrate the ability of HSV-1, HHV-6, and VZV antigens to induce higher RT activity in peripheral lymphocytes from MS patients vs. controls during the first 6 days post-antigen stimulation. On subsequent days, only VZV can sustain the increase in the RT expression...

  2. Increased T cell expression of CD154 (CD40-ligand) in multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Krakauer, M; Sellebjerg, F

    2001-01-01

    CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients with sec......CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients...

  3. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.

    Science.gov (United States)

    Kalincik, Tomas; Vivek, Vino; Jokubaitis, Vilija; Lechner-Scott, Jeannette; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Grand'maison, Francois; Hupperts, Raymond; Oreja-Guevara, Celia; Bergamaschi, Roberto; Iuliano, Gerardo; Alroughani, Raed; Van Pesch, Vincent; Amato, Maria Pia; Slee, Mark; Verheul, Freek; Fernandez-Bolanos, Ricardo; Fiol, Marcela; Spitaleri, Daniele La; Cristiano, Edgardo; Gray, Orla; Cabrera-Gomez, Jose Antonio; Shaygannejad, Vahid; Herbert, Joseph; Vucic, Steve; Needham, Merilee; Petkovska-Boskova, Tatjana; Sirbu, Carmen-Adella; Duquette, Pierre; Girard, Marc; Grammond, Pierre; Boz, Cavit; Giuliani, Giorgio; Rio, Maria Edite; Barnett, Michael; Flechter, Shlomo; Moore, Fraser; Singhal, Bhim; Bacile, Elizabeth Alejandra; Saladino, Maria Laura; Shaw, Cameron; Skromne, Eli; Poehlau, Dieter; Vella, Norbert; Spelman, Timothy; Liew, Danny; Kilpatrick, Trevor J; Butzkueven, Helmut

    2013-12-01

    The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10(-12)). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.

  4. {sup 11}C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunkyung; Gallezot, Jean-Dominique; Planeta, Beata; Lin, Shu-Fei; Lim, Keunpoong; Chen, Ming-Kai; Huang, Yiyun; Carson, Richard E. [Yale School of Medicine, PET Center, Department of Diagnostic Radiology, 801 Howard Avenue, PO Box 208048, New Haven, CT (United States); Delgadillo, Aracely; Liu, Shuang; O' Connor, Kevin C.; Lee, Jae-Yun; Chastre, Anne; Pelletier, Daniel [Yale School of Medicine, Department of Neurology, New Haven, CT (United States); Seneca, Nicholas; Leppert, David [Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel (Switzerland)

    2015-04-02

    Activated microglia play a key role in inflammatory demyelinating injury in multiple sclerosis (MS). Microglial activation can be measured in vivo using a positron emission tomography (PET) ligand {sup 11}C-PBR28. We evaluated the test-retest variability (TRV) and lesion detectability of {sup 11}C-PBR28 binding in MS subjects and healthy controls (HCs) with high-resolution PET. Four clinically and radiologically stable relapsing-remitting MS subjects (age 41 ± 7 years, two men/two women) and four HCs (age 42 ± 8 years, 2 two men/two women), matched for translocator protein genotype [two high- and two medium-affinity binders according to DNA polymorphism (rs6971) in each group], were studied for TRV. Another MS subject (age 41 years, male) with clinical and radiological activity was studied for lesion detectability. Dynamic data were acquired over 120 min after injection of 634 ± 101 MBq {sup 11}C-PBR28. For the TRV study, subjects were scanned twice, on average 1.4 weeks apart. Volume of distribution (V{sub T}) derived from multilinear analysis (MA1) modeling (t* = 30 min, using arterial input data) was the main outcome measure. Mean test V{sub T} values (ml cm{sup -3}) were 3.9 ± 1.4 in the whole brain gray matter (GM), 3.6 ± 1.2 in the whole brain white matter (WM) or normal-appearing white matter (NAWM), and 3.3 ± 0.6 in MS WM lesions; mean retest V{sub T} values were 3.7 ± 1.0 in GM, 3.3 ± 0.9 in WM/NAWM, and 3.3 ± 0.7 in MS lesions. Test-retest results showed a mean absolute TRV ranging from 7 to 9 % across GM, WM/NAWM, and MS lesions. High-affinity binders demonstrated 30 % higher V{sub T} than medium-affinity binders in GM. Focal {sup 11}C-PBR28 uptake was detected in two enhancing lesions of the active MS patient. High-resolution {sup 11}C-PBR28 PET can visualize focal areas where microglial activation is known to be present and has good test-retest reproducibility in the human brain. {sup 11}C-PBR28 PET is likely to be valuable for monitoring both

  5. Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Shahin Aeinehband

    Full Text Available Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE, an enzyme hydrolyzing acetylcholine (ACh, a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL, a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE and BuChE, in cerebrospinal fluid (CSF from patients with MS (n = 48 and non-inflammatory controls (n = 18. C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  6. Cesarean section and offspring's risk of multiple sclerosis

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  7. Studies based on the Danish Multiple Sclerosis Registry

    DEFF Research Database (Denmark)

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

    2011-01-01

    Introduction: This paper reviews the most important articles using data from the Danish Multiple Sclerosis Registry (DMSR) published in the past 25 years. Research topics: These articles include: descriptive epidemiological studies, indicating that the female incidence of multiple sclerosis (MS......) in Denmark has increased considerably; follow-up studies on social events, showing that patients at a high rate lose their working ability and their spouses/partners; mortality studies, demonstrating a considerable excess mortality; cause-of-death studies; comorbidity studies; and, most importantly...

  8. Metabolic reprogramming of mononuclear phagocytes and progressive multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Stefano ePluchino

    2015-03-01

    Full Text Available Multiple sclerosis (MS is an inflammatory and demyelinating disease of the central nervous system (CNS. Accumulation of brain damage in progressive MS is partly the result of mononuclear phagocytes (MPs attacking myelin sheaths in the CNS. Although there is no cure yet for MS, significant advances have been made in the development of disease modifying agents. Unfortunately, most of these drugs fail to reverse established neurological deficits and can have adverse effects. Recent evidence suggests that MPs polarisation is accompanied by profound metabolic changes, whereby pro-inflammatory MPs (M1 switch toward glycolysis, whereas anti-inflammatory MPs (M2 become more oxidative. It is therefore possible that reprogramming MPs metabolism could affect their function and repress immune cell activation. This minireview describes the metabolic changes underpinning macrophages polarisation and anticipates how metabolic re-education of MPs could be used for the treatment of MS.

  9. Analysis of CYP27B1 in multiple sclerosis

    Science.gov (United States)

    Ross, Jay P; Bernales, Cecily Q; Lee, Joshua D; Sadovnick, A Dessa; Traboulsee, Anthony L; Vilariño-Güell, Carles

    2016-01-01

    The analysis of genetic variability in CYP27B1 and its effect on risk of multiple sclerosis (MS) has yielded conflicting results. Here we describe a study to genetically characterize CYP27B1 and elucidate its role on MS risk in the Canadian population. Sequencing CYP27B1 failed to identify mutations known to cause loss of enzymatic activity, however genotyping of p.R389H in cases and controls identified the mutation in one multi-incident family (allele frequency = 0.03%) in which the p.R389H mutation segregates with disease in five family members diagnosed with MS, thus providing additional support for CYP27B1 p.R389H in the pathogenicity of MS. PMID:24308945

  10. Impaired Object Handling during Bimanual Task Performance in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stacey L. Gorniak

    2014-01-01

    Full Text Available We investigated the kinetic features of manual dexterity and fine motor control during a task that resembles an activity of daily living in 30 persons with relapsing-remitting multiple sclerosis (PwMS. Specifically, a novel two-transducer system was used to measure time and grip-load forces during a bimanual task that is similar to opening and closing a jar. We hypothesized that PwMS would have increased grip force production, deteriorations in kinetic timing, and preserved grip-load coupling indices compared to healthy controls (i.e., young and older adults. Increased grip force production and deterioration in timing indices were confirmed in PwMS. Abnormal grip-load coupling was exhibited by PwMS, in contrast to healthy participants. The correlation between task time and self-reported disability scores suggests that objective measurement of impaired upper-extremity movements relates to perception of overall function.

  11. Extracellular vesicles in multiple sclerosis: what are they telling us?

    Directory of Open Access Journals (Sweden)

    Matías eSáenz-Cuesta

    2014-03-01

    Full Text Available Extracellular vesicles (EVs are membrane-bound particles secreted by almost all cell types. They are classified depending on their biogenesis and size into exosomes and microvesicles or according to their cell origin. EVs play a role in cell-to-cell communication, including contact-free cell synapsis, carrying active membrane proteins, lipids, and genetic material both inside the particle and on their surface. They have been related to several physiological and pathological conditions. In particular, increasing concentrations of EVs have been found in many autoimmune diseases including multiple sclerosis (MS. MS is a central nervous system demyelinating disease characterized by relapsing of symptoms followed by periods of remission. Close interaction between endothelial cells, leukocytes, monocytes and cells from central nervous system is crucial for the development of MS. This review summarizes the pathological role of EVs in MS and the relationship of EVs with clinical characteristics, therapy and biomarkers of the disease.

  12. Expression and activation by Epstein Barr virus of human endogenous retroviruses-W in blood cells and astrocytes: inference for multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Giuseppe Mameli

    Full Text Available BACKGROUND: Proposed co-factors triggering the pathogenesis of multiple sclerosis (MS are the Epstein Barr virus (EBV, and the potentially neuropathogenic MSRV (MS-associated retrovirus and syncytin-1, of the W family of human endogenous retroviruses. METHODOLOGY/PRINCIPAL FINDINGS: In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350, was studied on peripheral blood mononuclear cells (PBMC from healthy volunteers and MS patients, and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-κB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines. CONCLUSIONS/SIGNIFICANCE: In vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as

  13. Blockade of Ca2+-activated K+ channels in T cells: an option for the treatment of multiple sclerosis?

    DEFF Research Database (Denmark)

    Madsen, Lars Siim; Christophersen, Palle; Olesen, Søren-Peter

    2005-01-01

    Voltage- and Ca(2+)-dependent K(+) channels in the membrane of both T and B lymphocytes are important for the cellular immune response. In the current issue of the European Journal of Immunology, Reich et al. demonstrate that selective blockade of the intermediate-conductance Ca(2+)-activated K(+...... of new immune-suppressant drugs for the treatment of autoimmune diseases....

  14. Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid

    Science.gov (United States)

    Kaushik, Deepak K.; Yong, Heather Y. F.; Hahn, Jennifer N.; Silva, Claudia; Casha, Steven; Hurlbert, R. John; Jacques, Francois H.; Lisak, Robert; Khan, Omar; Ionete, Carolina; Larochelle, Catherine; Prat, Alex; Bar-Or, Amit; Yong, V. Wee

    2016-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS. PMID:27727297

  15. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin

    2011-01-01

    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS...

  16. Multiple Sclerosis: Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, John Cantú

    Science.gov (United States)

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

  17. Drugs in development for relapsing multiple sclerosis.

    Science.gov (United States)

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  18. Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines.

    Science.gov (United States)

    Gold, Ralf; Oreja-Guevara, Celia

    2013-12-01

    Symptomatic therapy of multiple sclerosis (MS) is an important part of a comprehensive treatment plan that aims to improve patients' quality of life. In the current era of medical progress, several factors have led to the development of guidelines for MS management. There is continued need for an evidence-based approach supported by high-quality data from controlled clinical trials. Most healthcare systems require this approach and include it in the reimbursement process. Guidelines are usually committed by national or continental neurological societies. The Spanish Society of Neurology demyelinating diseases working group has developed a consensus document on spasticity in patients with MS. MS experts from the group used the metaplan method to sum up the most important recommendations about spasticity for inclusion in the guidance. Recommendations were classified according to the Scottish Intercollegiate Guidelines Network system and approved by all members of the group. In Germany, the guideline panel of the German Neurological Society endorsed the national competence network for multiple sclerosis (Krankheitsbezogenes Kompetenznetz Multiple Sklerose) to update the existing recommendations. The most recent fifth edition of the guidelines (dated April 2012) now also includes recommendations for treatment of key symptoms such as spasticity. More than 30 MS neurologists contributed to the new edition reflecting the need for broad expertise. After a first round in which key topics were defined, a web-based decision process was undertaken to further develop individual topics such as symptomatic therapy. The draft manuscript was reviewed once again by the group prior to submission to the official review process. The aims of spasticity treatment are to improve mobility and dexterity, achieve physiological movement patterns, reduce pain, facilitate nursing measures and avoid complications such as contractures. Representative antispasticity medications include baclofen

  19. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P;

    2001-01-01

    Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5...

  20. Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016.

    Science.gov (United States)

    García Merino, A; Ramón Ara Callizo, J; Fernández Fernández, O; Landete Pascual, L; Moral Torres, E; Rodríguez-Antigüedad Zarrantz, A

    2017-03-01

    With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs.

  1. No evidence for spumavirus or oncovirus infection in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Svenningsson, A; Lycke, J; Svennerholm, B; Gronowitz, S; Andersen, O

    1992-11-01

    Polymerase chain reaction analysis was used to investigate the possible role of human spumaretrovirus and oncoretroviruses (human T-cell lymphotropic virus types I [HTLV-I] and II [HTLV-II]) in multiple sclerosis. Eleven patients with relapsing-remitting multiple sclerosis in exacerbation and 11 normal blood donors were included in the study. Cerebrospinal fluid cells, peripheral blood mononuclear cells, and plasma were cocultured with allogeneic mononuclear cells for 6 weeks. Cultured cells were subjected to polymerase chain reaction analysis with primers selected for the pol and gag (human spumaretrovirus), pol and env (HTLV-I), and pol (HTLV-II) genes. Polymerase chain reaction was negative in all patient and blood donor control samples, whereas positive controls were consistently reactive with high sensitivity. No culture exhibited cytopathic effects and supernatants were negative for reverse transcriptase activity. Thus, our results do not support a role for these retroviruses in the pathogenesis of multiple sclerosis.

  2. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression.

    Directory of Open Access Journals (Sweden)

    Jeppe Romme Christensen

    Full Text Available Pathology studies of progressive multiple sclerosis (MS indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4(+ and CD8(+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+TFH-cells in peripheral blood from relapsing-remitting (RRMS and secondary progressive (SPMS MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor(+CD4(+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+ and CD83(+B-cells in SPMS. ICOS(+TFH-cells and DC-SIGN(+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings

  3. Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal.

    Science.gov (United States)

    Davion, Jean-Baptiste; Cambron, M; Duhin, E; Chouraki, A; Lacour, A; Labauge, P; Carra, C; Ayrignac, X; Vermersch, P

    2016-07-01

    We report two cases of primary progressive multiple sclerosis (PPMS) included in the INFORMS cohort, experiencing a relapse related to a single MRI gadolinium-enhancing lesion 3 months after fingolimod withdrawal. These two patients share similarities with relapsing-remitting multiple sclerosis cases described in the same situation, suggesting that the initiating process of the active demyelinating plaques is also present in PPMS, even without relapses, but may be triggered as fingolimod is withdrawn. Although the results of the INFORMS study suggest that fingolimod may not slow down the progression, some PPMS patients might still benefit from a disease-modifying treatment.

  4. Disease-modifying therapies in relapsing–remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Fabricio González-Andrade

    2010-07-01

    Full Text Available Fabricio González-Andrade1, José Luis Alcaraz-Alvarez21Department of Medicine, Metropolitan Hospital, Quito, Ecuador; 2School of Medicine, University of Mayab, Merida, MexicoClinical question: What is the best current disease-modifying therapy for relapsing–remitting multiple sclerosis?Results: The evidence shows that the most effective disease-modifying therapy for delaying short- to medium-term disability progression, prevention of relapses, reducing the area and activity of lesions on magnetic resonance imaging, with the least side effects, is high-dose, high-frequency subcutaneous interferon-β1a 44 μg three times per week.Implementation: The pitfalls in treatment of MS can be avoided by remembering the following points: • The most effective therapy to prevent or delay the appearance of permanent neurological disability with the fewest side effects should be chosen, and treatment should not be delayed.• Adherence to treatment should be monitored closely, and needs comprehensive patient information and education to establish long-term adherence, which is a critical determinant of long-term outcome.• The correct approach to the disease includes disease management, symptom management, and patient management. A combination of tools is necessary to ease the various symptoms, which fall into three broad categories, i.e. rehabilitation, pharmacological, and procedural.• It is important to understand that no treatment modality should be used alone, unless it is in itself sufficient to remedy the particular symptom/problem.Keywords: relapsing–remitting multiple sclerosis, interferon, disease-modifying therapy, relapse prevention

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

    Science.gov (United States)

    Mackenzie, Catherine; Green, Jan

    2009-01-01

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

  6. Motivational and Volitional Variables Associated with Stages of Change for Exercise in Multiple Sclerosis: A Multiple Discriminant Analysis

    Science.gov (United States)

    Chiu, Chung-Yi; Fitzgerald, Sandra D.; Strand, David M.; Muller, Veronica; Brooks, Jessica; Chan, Fong

    2012-01-01

    The main objective of this study was to determine whether motivational and volitional variables identified in the health action process approach (HAPA) model can be used to successfully differentiate people with multiple sclerosis (MS) in different stages of change for exercise and physical activity. Ex-post-facto design using multiple…

  7. Multiple Sclerosis in Pediatrics: Current Concepts and Treatment Options

    NARCIS (Netherlands)

    Jancic, J. (Jasna); Nikolic, B. (Blazo); Ivancevic, N. (Nikola); Djuric, V. (Vesna); Zaletel, I. (Ivan); Stevanovic, D. (Dejan); Peric, S. (Sasa); J.N. van den Anker (John); J. Samardzic (Janko)

    2016-01-01

    textabstractMultiple sclerosis (MS) is a chronic, autoimmune, inflammatory, demyelinating disease of the central nervous system. MS is increasingly recognized in the pediatric population, and it is usually diagnosed around 15 years of age. The exact etiology of MS is still not known, although autoim

  8. Progress in the diagnosis and treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Shi-fang HOU

    2014-10-01

    Full Text Available The growing number of disease modifying drugs (DMDs approved for multiple sclerosis (MS treatment is a significant step forward and provides new options for MS patients. This article summarizes the clinical research highlights of MS, including clinical manifestations, accessory examinations, diagnostic criteria and progress of treatment. doi: 10.3969/j.issn.1672-6731.2014.10.004

  9. The use of valproic acid and multiple sclerosis

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect. OBJECTIVE...

  10. Multiple sclerosis brain lesion measurements in clinical practice

    OpenAIRE

    2014-01-01

    Jain S., Smeets D., Sima D., Van Hecke W., Loeckx D., Van Huffel S., Maes F., ''Multiple sclerosis brain lesion measurements in clinical practice'', European journal of neurology, vol. 21 suppl. s1, pp. 345, 2014 (Joint congress of European neurology, May 31 - June 3, 2014, Istanbul, Turkey).

  11. Oligoclonal bands predict multiple sclerosis after optic neuritis

    DEFF Research Database (Denmark)

    Skov, A G; Skov, T; Frederiksen, J L

    2011-01-01

    Multiple sclerosis (MS) is an autoimmune disease resulting in inflammation and demyelination of neurones in the central nervous system (CNS). The first sign of MS is often monosymptomatic optic neuritis (MON). Cerebrospinal fluid from a patient with MS analysed by electrophoresis often shows...

  12. Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars;

    2016-01-01

    BACKGROUND: There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. OBJECTIVE: To evaluate the effect of monthly oral...

  13. Risk Factors in Cause and Course of Multiple Sclerosis

    NARCIS (Netherlands)

    N. Jafari (Naghmeh)

    2012-01-01

    textabstractMultiple sclerosis (MS) is a leading non-traumatic cause of disability in young adults. It is a chronic neurological disorder characterized primarily by central nervous system (CNS) inflammation, myelin loss, and axonal pathology, resulting in progressive neurological dysfunction. Initia

  14. The role of the cerebellum in multiple sclerosis

    DEFF Research Database (Denmark)

    Weier, Katrin; Banwell, Brenda; Cerasa, Antonio

    2015-01-01

    In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, whi...

  15. Vision and vision-related outcome measures in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2015-01-01

    of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes...

  16. Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Caterina Motta

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

  17. Association of autoimmune hepatitis and multiple sclerosis: a coincidence?

    Directory of Open Access Journals (Sweden)

    Marta Sofia Mendes Oliveira

    2015-09-01

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

  18. Quality control for retinal OCT in multiple sclerosis

    DEFF Research Database (Denmark)

    Schippling, S; Balk, Lj; Costello, F;

    2015-01-01

    BACKGROUND: Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. OBJECTIVE: An expert task force convened with the aim to pr...

  19. Principles of a new treatment algorithm in multiple sclerosis

    DEFF Research Database (Denmark)

    Hartung, Hans-Peter; Montalban, Xavier; Sorensen, Per Soelberg;

    2011-01-01

    We are entering a new era in the management of patients with multiple sclerosis (MS). The first oral treatment (fingolimod) has now gained US FDA approval, addressing an unmet need for patients with MS who wish to avoid parenteral administration. A second agent (cladribine) is currently being...

  20. Exercise and Quality of Life in Women with Multiple Sclerosis

    Science.gov (United States)

    Giacobbi, Peter R., Jr.; Dietrich, Frederick; Larson, Rebecca; White, Lesley J.

    2012-01-01

    The purpose of this study was to evaluate perceptions of quality of life after a 4-month progressive resistance training program for individuals with multiple sclerosis (MS). A second purpose was to examine participants' views about factors that facilitated or impeded exercise behavior. Qualitative interviews were conducted with eight females…

  1. Evaluating Functional Decline in Patients with Multiple Sclerosis

    Science.gov (United States)

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

    Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

  2. Multiple sclerosis, remyelination and the role of fibronectin

    NARCIS (Netherlands)

    Stoffels, Josephine

    2014-01-01

    Our central nervous system functions, among others, thanks to myelin. Myelin is a fatty layer of insulation among nervous cells, which is produced by specific cells, namely oligodendrocytes. Multiple sclerosis (MS) is a disease that damages myelin. These myelin injuries (lesions) seem largely respon

  3. Sun Exposure and Reduced Risk of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2008-09-01

    Full Text Available The association between red hair color (RHC melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis (MS was investigated in a population-based case-control study in Tasmania, Australia, involving 136 cases with MS and 272 controls.

  4. Laboratory diagnosis of multiple sclerosis. Laboratoriediagnostikk ved multippel sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Sand, T.; Stovner, L.J.; Rinck, P.A.; Nilsen, G.; Romslo, I. (University and Regional Hospital, Trondheim (Norway))

    1991-08-01

    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.

  5. Decreased Postural Balance in Multiple Sclerosis Patients with Low Disability

    Science.gov (United States)

    Fjeldstad, Cecilie; Pardo, Gabriel; Bemben, Debra; Bemben, Michael

    2011-01-01

    To evaluate balance in women with multiple sclerosis (MS) who have low disability and minimal clinical impairments as measured by the Expanded Disability Status Scale (EDSS), and compare them with healthy age-matched controls. Patients were aged between 18 and 64 years; 67 individuals with MS (mu = 44.0 plus or minus 1.2 years) and 45 healthy…

  6. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H;

    2015-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on ...

  7. Modifiable factors influencing relapses and disability in multiple sclerosis

    NARCIS (Netherlands)

    D'hooghe, M. B.; Nagels, G.; Bissay, V.; De Keyser, J.

    2010-01-01

    A growing body of literature indicates that the natural course of multiple sclerosis can be influenced by a number of factors. Strong evidence suggests that relapses can be triggered by infections, the postpartum period and stressful life events. Vaccinations against influenza, hepatitis B and tetan

  8. Self and Body Esteem Perception in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Yoram Barak

    1999-01-01

    Full Text Available Self esteem and body esteem were examined in a group of 35 relapsing-remitting multiple sclerosis (MS patients using the Body Esteem Scale (BES and the Eysenck Self Esteem Scale (ESES and compared to age and sex matched normal controls.

  9. Relevance of anti-myelin antibodies in Multiple Sclerosis

    NARCIS (Netherlands)

    Breij, E.C.W.

    2005-01-01

    Antibodies directed against myelin antigens have been described in multiple sclerosis (MS). Although anti-myelin antibodies have been implicated in central nervous system (CNS) demyelination, it is unclear to what extent anti-myelin antibodies contribute to MS pathogenesis. In this dissertation,

  10. Are astrocytes central players in the pathophysiology of multiple sclerosis?

    NARCIS (Netherlands)

    De Keyser, J; Zeinstra, E; Frohman, E

    2003-01-01

    An interaction between antimyelin T cells and antigen-presenting glial cells is a crucial step in the cascade of immune events that lead to the inflammatory lesions in multiple sclerosis (MS). One of the most debated and controversial issues is whether microglial cells or astrocytes are the key play

  11. EBV Infection and Multiple Sclerosis : Lessons from a Marmoset Model

    NARCIS (Netherlands)

    Hart, 't Bert; Kap, Yolanda S.; Morandi, Elena; Laman, Jon D.; Gran, Bruno

    2016-01-01

    Multiple sclerosis (MS) is thought to be initiated by the interaction of genetic and environmental factors, eliciting an autoimmune attack on the central nervous system. Epstein-Barr virus (EBV) is the strongest infectious risk factor, but an explanation for the paradox between high infection preval

  12. Interplay between mechanisms of damage and repair in multiple sclerosis.

    Science.gov (United States)

    Stadelmann, Christine; Brück, Wolfgang

    2008-03-01

    The neuropathology of multiple sclerosis is characterised by focal damage to white matter. However, tissue damage is also present in the cortical grey matter, with a particularly high prevalence of cortical demyelination being observed in secondary progressive and primary progressive forms of the disease. The presence of meningeal B-cell follicle-like structures, which frequently appear during the secondary progressive phase of disease, may be involved in the formation of these subpial cortical lesions. Diffuse white matter inflammation accompanied by axonal damage can also be observed in normal appearing white matter and, again, this is more prominent in chronic progressive forms of multiple sclerosis than in acute stages of disease. Axonal damage is a particularly important component of the pathology of multiple sclerosis and appears to be a critical determinant of clinical outcome. Axons appear to become vulnerable to injury as a result of loss of their myelin sheaths. Remyelination represents an important mechanism of tissue repair in multiple sclerosis and already occurs at an early stage of lesion development and in both white and grey matter lesions. The extent of remyelination appears to be greater in cortical lesions and in lesions further from the ventricles. There is important heterogeneity between patients in terms of the extent of remyelination, which may reflect underlying differences in pathogenetic mechanisms between patients.

  13. EAE : imperfect but useful models of multiple sclerosis

    NARCIS (Netherlands)

    't Hart, Bert A.; Gran, Bruno; Weissert, Robert

    2011-01-01

    The high failure rate of immunotherapies in multiple sclerosis (MS) clinical trials demonstrates problems in translating new treatment concepts from animal models to the patient. One main reason for this 'immunotherapy gap' is the usage of immunologically immature, microbiologically clean and geneti

  14. The insulin-like growth factor system in multiple sclerosis

    NARCIS (Netherlands)

    Chesik, Daniel; Wilczak, Nadine; De Keyser, Jacques

    2007-01-01

    Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease

  15. From etiology and pathogenesis to therapy of multiple sclerosis.

    Science.gov (United States)

    Cazzullo, C L

    1978-01-31

    The Author describes the histopathologic picture of the Multiple Sclerosis and Experimental Allergic Encephalitis and discusses some etiopathogenetic hypotheses elaborating on the immunogenetic and immunopathological aspects. The therapeutical problem is analyzed in all its various facets: cortisone derivatives, immunosuppressive products and reabilitation therapy aiming simultaneously at motion reeducation and at individual and group psycotherapy.

  16. Cytomegalovirus : a culprit or protector in multiple sclerosis?

    NARCIS (Netherlands)

    Vanheusden, Marjan; Stinissen, Piet; 't Hart, Bert A.; Hellings, Niels

    2015-01-01

    Multiple sclerosis (MS) is a chronic disabling autoimmune disease of the central nervous system (CNS). Cytomegalovirus (CMV), a beta herpes virus, may have a detrimental or beneficial role in MS pathology. Accumulating evidence indicates that CMV contributes to MS disease via interplay of different

  17. Clinical Manifestations of Multiple Sclerosis in Taiwanese Children

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-11-01

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

  18. Improved patient-reported health impact of multiple sclerosis

    DEFF Research Database (Denmark)

    Macdonell, Richard; Nagels, Guy; Laplaud, David-Axel

    2016-01-01

    BACKGROUND: Multiple sclerosis (MS) is a debilitating disease that negatively impacts patients' lives. OBJECTIVE: ENABLE assessed the effect of long-term prolonged-release (PR) fampridine (dalfampridine extended release in the United States) treatment on patient-perceived health impact in patients...

  19. Workflow Management for Multiple Sclerosis Patients: IT and Organization

    NARCIS (Netherlands)

    Michel-Verkerke, Margreet B.; Schuring, Roel W.; Spil, Ton A.M.; Sprague, R.H.

    2004-01-01

    Patients with Multiple Sclerosis (MS) visit various healthcare providers during the course of their disease. It was suggested that IT might help to orchestrate their care provision. We have applied the USE IT-tool to get insight in the relevant problems, solutions and constraints of the MS-care and

  20. Geographical and seasonal correlation of multiple sclerosis to sporadic schizophrenia

    Directory of Open Access Journals (Sweden)

    Fritzsche Markus

    2002-12-01

    Full Text Available Abstract Background Clusters by season and locality reveal a striking epidemiological overlap between sporadic schizophrenia and multiple sclerosis (MS. As the birth excesses of those individuals who later in life develop schizophrenia mirror the seasonal distribution of Ixodid ticks, a meta analysis has been performed between all neuropsychiatric birth excesses including MS and the epidemiology of spirochaetal infectious diseases. Results The prevalence of MS and schizophrenic birth excesses entirely spares the tropical belt where human treponematoses are endemic, whereas in more temperate climates infection rates of Borrelia garinii in ticks collected from seabirds match the global geographic distribution of MS. If the seasonal fluctuations of Lyme borreliosis in Europe are taken into account, the birth excesses of MS and those of schizophrenia are nine months apart, reflecting the activity of Ixodes ricinus at the time of embryonic implantation and birth. In America, this nine months' shift between MS and schizophrenic births is also reflected by the periodicity of Borrelia burgdorferi transmitting Ixodes pacificus ticks along the West Coast and the periodicity of Ixodes scapularis along the East Coast. With respect to Ixodid tick activity, amongst the neuropsychiatric birth excesses only amyotrophic lateral sclerosis (ALS shows a similar seasonal trend. Conclusion It cannot be excluded at present that maternal infection by Borrelia burgdorferi poses a risk to the unborn. The seasonal and geographical overlap between schizophrenia, MS and neuroborreliosis rather emphasises a causal relation that derives from exposure to a flagellar virulence factor at conception and delivery. It is hoped that the pathogenic correlation of spirochaetal virulence to temperature and heat shock proteins (HSP might encourage a new direction of research in molecular epidemiology.

  1. 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.

  2. 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.

  3. A Qualitative Study of Multiple Health Behaviors in Adults with Multiple Sclerosis

    Science.gov (United States)

    Golding, Meghan

    2016-01-01

    Background: Evidence regarding inflammatory pathways, elevated cardiovascular risk, and negative effects of secondary conditions on disability progression provide a strong rationale for promoting multiple health behaviors in adults with multiple sclerosis (MS). However, many unanswered questions remain about the best ways to design multiple behavior change interventions for adults with MS. We sought to identify facilitators and barriers to engaging in multiple health behaviors (physical activity, nutrition, and sleep) and to gain further insights into how to develop multiple health behavior change interventions based on preferences of adults with MS. Methods: Focus groups and one-on-one interviews were conducted with 17 participants with MS. Results: Five qualitative themes were identified as either facilitating or hindering engagement in multiple health behaviors: 1) roles, priorities, and preferences; 2) sense of duty; 3) the fatigue and mobility problem; 4) taking control; and 5) resiliency. Participants identified advantages and disadvantages of delivery formats (eg, face-to-face group vs. telephone), frequency of contacts, and intervention strategies based on their individual circumstances and obligations. Participants felt that discussing the benefits of engaging in multiple health behaviors, developing action plans, accommodating preferences, and addressing health problems would be helpful strategies to include in a multiple behavior change intervention. Conclusions: These findings indicate that there may be common facilitators and barriers that can be targeted to promote multiple behavior changes. Future research should explore the best ways to tailor multiple behavior change interventions to preferences, symptoms, psychological traits, and social cognitions. PMID:27803640

  4. CCR5 in Multiple Sclerosis : expression, regulation, and modulation by statins

    NARCIS (Netherlands)

    Kuipers, Hedwich Fardau

    2007-01-01

    Activation of microglia, the macrophages of the central nervous system, is a key element in multiple sclerosis (MS) lesion development and is characterized by enhanced expression of both classes of major histocompatibility complex (MHC) molecules. This enhanced expression results from increased leve

  5. Phase II study of oral fingolimod (FTY720) in multiple sclerosis: 3-year results

    DEFF Research Database (Denmark)

    Comi, G; O'Connor, P; Montalban, X;

    2010-01-01

    In a 6-month, placebo-controlled trial, oral fingolimod (FTY720) 1.25 or 5.0 mg, once daily, significantly reduced MRI inflammatory activity and annualized relapse rate compared with placebo in patients with relapsing multiple sclerosis (MS). The objectives were to monitor the 36-month, interim e...

  6. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

    DEFF Research Database (Denmark)

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A;

    2010-01-01

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI...

  7. Tissue transglutaminase in Marmoset experimental multiple sclerosis : Discrepancy between white and grey matter

    NARCIS (Netherlands)

    Pinzon, Nathaly Espitia; Stroo, Esther; 't Hart, Bert A.; Bol, John G. J. M.; Drukarch, Benjamin; Bauer, Jan; van Dam, Anne-Marie

    2014-01-01

    Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of beta-integrins with extracell

  8. 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...

  9. 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...

  10. Predictors and dynamics of postpartum relapses in women with multiple sclerosis

    NARCIS (Netherlands)

    Hughes, Stella E; Spelman, Tim; Gray, Orla M; Boz, Cavit; Trojano, Maria; Lugaresi, Alessandra; Izquierdo, Guillermo; Duquette, Pierre; Girard, Marc; Grand'Maison, Francois; Grammond, Pierre; Oreja-Guevara, Celia; Hupperts, Raymond; Bergamaschi, Roberto; Giuliani, Giorgio; Lechner-Scott, Jeannette; Barnett, Michael; Edite Rio, Maria; van Pesch, Vincent; Amato, Maria Pia; Iuliano, Gerardo; Slee, Mark; Verheul, Freek; Cristiano, Edgardo; Fernández-Bolaños, Ricardo; Poehlau, Dieter; Saladino, Maria Laura; Deri, Norma; Cabrera-Gomez, Jose; Vella, Norbert; Herbert, Joseph; Skromne, Eli; Savino, Aldo; Shaw, Cameron; Moore, Fraser; Vucic, Steve; Petkovska-Boskova, Tatjana; McDonnell, Gavin; Hawkins, Stanley; Kee, Frank; Butzkueven, Helmut

    2014-01-01

    BACKGROUND: Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies. OBJECTIVE: To re-examine effect of pregnancy on relapses using

  11. Cognitive-Behavioral Classifications of Chronic Pain in Patients with Multiple Sclerosis

    Science.gov (United States)

    Khan, Fary; Pallant, Julie F.; Amatya, Bhasker; Young, Kevin; Gibson, Steven

    2011-01-01

    The aim of this study was to replicate, in patients with multiple sclerosis (MS), the three-cluster cognitive-behavioral classification proposed by Turk and Rudy. Sixty-two patients attending a tertiary MS rehabilitation center completed the Pain Impact Rating questionnaire measuring activity interference, pain intensity, social support, and…

  12. 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....

  13. An observational study of alemtuzumab following fingolimod for multiple sclerosis

    Science.gov (United States)

    Willis, Mark; Pearson, Owen; Illes, Zsolt; Sejbaek, Tobias; Nielsen, Christian; Duddy, Martin; Petheram, Kate; van Munster, Caspar; Killestein, Joep; Malmeström, Clas; Tallantyre, Emma

    2017-01-01

    Objective: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. Methods: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. Results: Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39–215) months and follow-up from time of first alemtuzumab cycle 20 (14–21) months. Following first alemtuzumab infusion cycle, 8 patients were identified by at least 1 clinical relapse and radiologic disease activity and 1 by significant radiologic disease activity alone. Conclusions: We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive lymphocytes following fingolimod withdrawal, allowing these cells to be concealed from the usual biological effect of alemtuzumab. Subsequent lymphocyte egress then provokes disease reactivation. Further animal studies and clinical trials are required to confirm these phenomena and in the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens. PMID:28101520

  14. Cytokines gene expression in newly diagnosed multiple sclerosis patients.

    OpenAIRE

    Seyed Javad Hasheminia; Sepideh Tolouei; Sayyed Hamid Zarkesh-Esfahani; Vahid Shaygannejad; Hedaiat Allah Shirzad; Reza Torabi; Morteza Hashem Zadeh Chaloshtory

    2015-01-01

    Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons. In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications w...

  15. Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Norma Y. Hernández-Pedro

    2013-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS.

  16. Initial immunopathogenesis of multiple sclerosis: innate immune response.

    Science.gov (United States)

    Hernández-Pedro, Norma Y; Espinosa-Ramirez, Guillermo; de la Cruz, Verónica Pérez; Pineda, Benjamín; Sotelo, Julio

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The hallmark to MS is the demyelinated plaque, which consists of a well-demarcated hypocellular area characterized by the loss of myelin, the formation of astrocytic scars, and the mononuclear cell infiltrates concentrated in perivascular spaces composed of T cells, B lymphocytes, plasma cells, and macrophages. Activation of resident cells initiates an inflammatory cascade, leading to tissue destruction, demyelination, and neurological deficit. The immunological phenomena that lead to the activation of autoreactive T cells to myelin sheath components are the result of multiple and complex interactions between environment and genetic background conferring individual susceptibility. Within the CNS, an increase of TLR expression during MS is observed, even in the absence of any apparent microbial involvement. In the present review, we focus on the role of the innate immune system, the first line of defense of the organism, as promoter and mediator of cross reactions that generate molecular mimicry triggering the inflammatory response through an adaptive cytotoxic response in MS.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  18. Disability profile of multiple sclerosis in New Zealand

    DEFF Research Database (Denmark)

    Alla, Sridhar; Pearson, John F.; Taylor, Bruce V.;

    2016-01-01

    New Zealand is a high risk region for multiple sclerosis (MS). The aim of this study was to investigate demographic, clinical and temporal factors associated with disability status in the New Zealand National Multiple Sclerosis Prevalence Study (NZNMSPS) cohort. Data were obtained from the 2006...... NZNMSPS with MS diagnosis based on the 2005 McDonald criteria. Disability was assessed using the Expanded Disability Status Scale (EDSS). Disability profiles were generated using multiple linear regression analysis. A total of 2917 persons with MS was identified, of whom disability data were available...... for 2422 (75% females). The overall disability was EDSS 4.4. ±. standard deviation 2.6. Higher disability was associated with older age, longer disease duration, older and younger ages of onset, spinal cord syndromes with motor involvement at onset, and a progressive onset type. Lower disability...

  19. Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination

    Directory of Open Access Journals (Sweden)

    Edward L. Hogan

    2013-08-01

    Full Text Available Multiple sclerosis (MS is the most common demyelinating and an autoimmune disease of the central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. T cell subsets (Th1, Th2, Th17, CD8+, NKT, CD4+CD25+ T regulatory cells and B cells are involved in this disorder, thus new MS therapies seek damage prevention by resetting multiple components of the immune system. The currently approved therapies are immunoregulatory and reduce the number and rate of lesion formation but are only partially effective. This review summarizes current understanding of the processes at issue: myelination, demyelination and remyelination—with emphasis upon myelin composition/ architecture and oligodendrocyte maturation and differentiation. The translational options target oligodendrocyte protection and myelin repair in animal models and assess their relevance in human. Remyelination may be enhanced by signals that promote myelin formation and repair. The crucial question of why remyelination fails is approached is several ways by examining the role in remyelination of available MS medications and avenues being actively pursued to promote remyelination including: (i cytokine-based immune-intervention (targeting calpain inhibition, (ii antigen-based immunomodulation (targeting glycolipid-reactive iNKT cells and sphingoid mediated inflammation and (iii recombinant monoclonal antibodies-induced remyelination.

  20. A passive exoskeleton can push your life up: application on multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Francesco Di Russo

    Full Text Available In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the "Human Body Posturizer", designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

  1. Safety concerns and risk management of multiple sclerosis therapies.

    Science.gov (United States)

    Soelberg Sorensen, P

    2016-11-27

    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 injections and are only moderately effective, but have very rarely life-threatening adverse effects, whereas teriflunomide and dimethyl fumarate are administered orally and have equal or better efficacy, but have more potentially severe adverse effects. The highly effective therapies fingolimod, natalizumab, daclizumab, and alemtuzumab have more serious adverse effects, some of which may be life-threatening. The choice between drugs should be based on a benefit-risk evaluation and tailored to the individual patient's requirements in a dialogue between the patient and treating neurologist. Patients with average 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.

  2. Anticipatory postural adjustments in individuals with multiple sclerosis.

    Science.gov (United States)

    Krishnan, Vennila; Kanekar, Neeta; Aruin, Alexander S

    2012-01-11

    Individuals with multiple sclerosis (MS) frequently exhibit difficulties in balance maintenance. It is known that anticipatory postural adjustments (APAs) play an important role in postural control. However, no information exists on how people living with MS utilize APAs for control of posture. A group of individuals with MS and a group of healthy control subjects performed rapid arm flexion and extension movements while standing on a force platform. Electromyographic (EMG) activity of six trunk and leg muscles and displacement of center of pressure (COP) were recorded and quantified within the time intervals typical of APAs. Individuals with MS demonstrated diminished ability to produce directional specific patterns of anticipatory EMGs as compared to control subjects. In addition, individuals with MS demonstrated smaller magnitudes of anticipatory muscle activation. This was associated with larger displacements of the COP during the balance restoration phase. These results suggest the importance of anticipatory postural control in maintenance of vertical posture in individuals with MS. The outcome of the study could be used while developing rehabilitation strategies focused on balance restoration in individuals with MS.

  3. Therapeutic strategies targeting B-cells in multiple sclerosis.

    Science.gov (United States)

    Milo, Ron

    2016-07-01

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T-cells. Increasing evidence, however, suggests the fundamental role of B-cells in the pathogenesis of the disease. Recent strategies targeting B-cells in MS have demonstrated impressive and sometimes surprising results: B-cell depletion by monoclonal antibodies targeting the B-cell surface antigen CD20 (e.g. rituximab, ocrelizumab, ofatumumab) was shown to exert profound anti-inflammatory effect in MS with favorable risk-benefit ratio, with ocrelizumab demonstrating efficacy in both relapsing-remitting (RR) and primary-progressive (PP) MS in phase III clinical trials. Depletion of CD52 expressing T- and B-cells and monocytes by alemtuzumab resulted in impressive and durable suppression of disease activity in RRMS patients. On the other hand, strategies targeting B-cell cytokines such as atacicept resulted in increased disease activity. As our understanding of the biology of B-cells in MS is increasing, new compounds that target B-cells continue to be developed which promise to further expand the armamentarium of MS therapies and allow for more individualized therapy for patients with this complex disease.

  4. Black holes in multiple sclerosis: definition, evolution, and clinical correlations.

    Science.gov (United States)

    Sahraian, M A; Radue, E-W; Haller, S; Kappos, L

    2010-07-01

    Magnetic resonance imaging (MRI) is a sensitive paraclinical test for diagnosis and assessment of disease progression in multiple sclerosis (MS) and is often used to evaluate therapeutic efficacy. The formation of new T2-hyperintense MRI lesions is commonly used to measure disease activity, but lacks specificity because edema, inflammation, gliosis, and axonal loss all contribute to T2 lesion formation. As the role of neurodegeneration in the pathophysiology of MS has become more prominent, the formation and evolution of chronic or persistent Tl-hypointense lesions (black holes) have been used as markers of axonal loss and neuronal destruction to measure disease activity. Despite the use of various detection methods, including advanced imaging techniques such as magnetization transfer imaging and magnetic resonance spectroscopy, correlation of persistent black holes with clinical outcomes in patients with MS remains uncertain. Furthermore, although axonal loss and neuronal tissue destruction are known to contribute to irreversible disability in patients with MS, there are limited data on the effect of therapy on longitudinal change in Tl-hypointense lesion volume. Measurement of black holes in clinical studies may elucidate the underlying pathophysiology of MS and may be an additional method of evaluating therapeutic efficacy.

  5. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis

    Science.gov (United States)

    Ahmetspahic, Diana; Ruck, Tobias; Schulte-Mecklenbeck, Andreas; Schwarte, Kathrin; Jörgens, Silke; Scheu, Stefanie; Windhagen, Susanne; Graefe, Bettina; Melzer, Nico; Klotz, Luisa; Arolt, Volker; Wiendl, Heinz; Meuth, Sven G.

    2016-01-01

    Objective: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. Methods: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)–23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined. Results: In comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change. Conclusions: Our findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS. PMID:27766281

  6. Nuclear receptor NR1H3 in familial multiple sclerosis

    Science.gov (United States)

    Wang, Zhe; Sadovnick, A. Dessa; Traboulsee, Anthony L.; Ross, Jay P.; Bernales, Cecily Q.; Encarnacion, Mary; Yee, Irene M.; de Lemos, Madonna; Greenwood, Talitha; Lee, Joshua D.; Wright, Galen; Ross, Colin J.; Zhang, Si; Song, Weihong; Vilariño-Güell, Carles

    2016-01-01

    SUMMARY Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss and neuronal dysfunction. Despite the aggregation observed in some families, pathogenic mutations have remained elusive. In this study we describe the identification of NR1H3 p.Arg415Gln in seven MS patients from two multi-incident families presenting severe and progressive disease, with an average age at onset of 34 years. Additionally, association analysis of common variants in NR1H3 identified rs2279238 conferring a 1.35-fold increased risk of developing progressive MS. The p.Arg415Gln position is highly conserved in orthologs and paralogs, and disrupts NR1H3 heterodimerization and transcriptional activation of target genes. Protein expression analysis revealed that mutant NR1H3 (LXRA) alters gene expression profiles, suggesting a disruption in transcriptional regulation as one of the mechanisms underlying MS pathogenesis. Our study indicates that pharmacological activation of LXRA or its targets may lead to effective treatments for the highly debilitating and currently untreatable progressive phase of MS. PMID:27253448

  7. Methylglyoxal-Derived Advanced Glycation Endproducts in Multiple Sclerosis

    Science.gov (United States)

    Wetzels, Suzan; Wouters, Kristiaan; Schalkwijk, Casper G.; Vanmierlo, Tim; Hendriks, Jerome J. A.

    2017-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The activation of inflammatory cells is crucial for the development of MS and is shown to induce intracellular glycolytic metabolism in pro-inflammatory microglia and macrophages, as well as CNS-resident astrocytes. Advanced glycation endproducts (AGEs) are stable endproducts formed by a reaction of the dicarbonyl compounds methylglyoxal (MGO) and glyoxal (GO) with amino acids in proteins, during glycolysis. This suggests that, in MS, MGO-derived AGEs are formed in glycolysis-driven cells. MGO and MGO-derived AGEs can further activate inflammatory cells by binding to the receptor for advanced glycation endproducts (RAGE). Recent studies have revealed that AGEs are increased in the plasma and brain of MS patients. Therefore, AGEs might contribute to the inflammatory status in MS. Moreover, the main detoxification system of dicarbonyl compounds, the glyoxalase system, seems to be affected in MS patients, which may contribute to high MGO-derived AGE levels. Altogether, evidence is emerging for a contributing role of AGEs in the pathology of MS. In this review, we provide an overview of the current knowledge on the involvement of AGEs in MS. PMID:28212304

  8. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  9. Multiple Sclerosis and Catastrophic Health Expenditure in Iran

    Science.gov (United States)

    Juyani, Yaser; Hamedi, Dorsa; Hosseini Jebeli, Seyede Sedighe; Qasham, Maryam

    2016-01-01

    Background: There are many disabling medical conditions which can result in catastrophic health expenditure. Multiple Sclerosis is one of the most costly medical conditions through the world which encounter families to the catastrophic health expenditures. This study aims to investigate on what extent Multiple sclerosis patients face catastrophic costs. Method: This study was carried out in Ahvaz, Iran (2014). The study population included households that at least one of their members suffers from MS. To analyze data, Logit regression model was employed by using the default software STATA12. Results: 3.37% of families were encountered with catastrophic costs. Important variables including brand of drug, housing, income and health insurance were significantly correlated with catastrophic expenditure. Conclusions: This study suggests that although a small proportion of MS patients met the catastrophic health expenditure, mechanisms that pool risk and cost (e.g. health insurance) are required to protect them and improve financial and access equity in health care.

  10. Physical and social environment and the risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils; Pfleger, Claudia C.;

    2014-01-01

    BACKGROUND: The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men. The rapid epidemiological changes suggest that environmental factors may modify the risk of MS. OBJECTIVES: To investigate whether occupational, physical......, or social environmental influence the risk of MS differently in women than in men. METHODS: The cohort consists of all 1403 patients (939 women, 464 men) identified through Danish Multiple Sclerosis Registry aged 1-55 of years at clinical onset between 2000 and 2004, and up to 25 control persons for each...... case, matched by sex, year of birth and residential municipality. The same cohort was previously used to investigate the influence of the reproductive factors on the risk of MS. RESULTS: By linkage to Danish population registers we found a slight albeit statistically significant excess for 6 female MS...

  11. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    Science.gov (United States)

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  12. Theranostic Implications of Nanotechnology in Multiple Sclerosis: A Future Perspective

    Directory of Open Access Journals (Sweden)

    Ajay Vikram Singh

    2012-01-01

    Full Text Available Multiple Sclerosis is a multifactorial disease with several pathogenic mechanisms and pathways. Successful MS management and medical care requires early accurate diagnosis along with specific treatment protocols based upon multifunctional nanotechnology approach. This paper highlights advances in nanotechnology that have enabled the clinician to target the brain and CNS in patient with multiple sclerosis with nanoparticles having therapeutic and imaging components. The multipartite theranostic (thera(py + (diagnostics approach puts forth strong implications for medical care and cure in MS. The current nanotheranostics utilize tamed drug vehicles and contain cargo, targeting ligands, and imaging labels for delivery to specific tissues, cells, or subcellular components. A brief overview of nonsurgical nanorepair advances as future perspective is also described. Considering the potential inflammatory triggers in MS pathogenesis, a multifunctional nanotechnology approach will be needed for the prognosis.

  13. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    Science.gov (United States)

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  14. Management of Multiple Sclerosis in the Breastfeeding Mother

    OpenAIRE

    Saneea Almas; Jesse Vance; Teresa Baker; Thomas Hale

    2016-01-01

    Multiple Sclerosis (MS) is an autoimmune neurological disease characterized by inflammation of the brain and spinal cord. Relapsing-Remitting MS is characterized by acute attacks followed by remission. Treatment is aimed at halting these attacks; therapy may last for months to years. Because MS disproportionately affects females and commonly begins during the childbearing years, clinicians treat pregnant or nursing MS patients. The intent of this review is to perform an in-depth analysis into...

  15. Concurrence of Juvenile Idiopathic Arthritis and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Ben Abdelghani Kaouther

    2011-01-01

    Full Text Available We report a 21-year-old female patient known to have Juvenile idiopathic arthritis (JIA who later developed multiple sclerosis (MS. The disease was documented on the brain and cerebral magnetic resonance imaging (MRI and the visual evoked potential. Our case emphasizes the need to evaluate the symptoms and brain MRI carefully. The concurrence of MS and JIA is uncommon. The possible relationship between the 2 diseases was discussed.

  16. Peripheral Vasculitis, Intermediate Uveitis and Interferon Use in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Haluk Esgin

    2016-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system. A 40-year-old female patient with a 12-year history of MS was admitted to our clinic with blurred vision and floaters in her right eye for about 1 month. Here, we share the findings and the management of intermediate uveitis and retinal periphlebitis in an MS case being treated with interferon beta-1a for 7 years.

  17. HTLV antibodies in Italian patients with multiple sclerosis.

    Science.gov (United States)

    Varmier, O; Melioli, G; Lillo, F; Schito, G; Repetto, C; Ravegnani, M; Battaglia, M

    1987-06-01

    Several observations indicate that a retrovirus might be involved in the pathogenesis of multiple sclerosis (MS). We report that the sera from 40 Italian MS patients did not contain antibodies to the human T-lymphotropic type I (HTLV-I) and type III viruses (HTLV-III) at levels detectable by commercial ELISA kits. Nevertheless, it cannot be ruled out that a distinct retrovirus is the etiologic factor of MS.

  18. Exploring the origins of grey matter damage in multiple sclerosis

    OpenAIRE

    Calabrese, Massimiliano; Magliozzi, Roberta; Ciccarelli, Olga; Geurts, Jeroen J. G.; Reynolds, Richard; Martin, Roland

    2015-01-01

    Multiple sclerosis is characterized at the gross pathological level by the presence of widespread focal demyelinating lesions of the myelin-rich white matter. However, it is becoming clear that grey matter is not spared, even during the earliest phases of the disease. Furthermore, grey matter damage may have an important role both in physical and cognitive disability. Grey matter pathology involves both inflammatory and neurodegenerative mechanisms, but the relationship between the two is unc...

  19. Grey matter atrophy in patients suffering from multiple sclerosis.

    Science.gov (United States)

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László

    2014-09-30

    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  20. Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis

    DEFF Research Database (Denmark)

    Blinkenberg, M; Akeson, P; Sillesen, H;

    2012-01-01

    The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our...... aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology....

  1. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    OpenAIRE

    Julia Krämer; Meuth, Sven G.; Jan-Gerd Tenberge; Patrick Schiffler; Heinz Wiendl; Michael Deppe

    2015-01-01

    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 (IC...

  2. Natalizumab for the treatment of relapsing multiple sclerosis

    OpenAIRE

    Rudick, Richard A.; Michael A Panzara

    2008-01-01

    Richard A Rudick1, Michael A Panzara21Cleveland Clinic Foundation, Cleveland, OH, USA; 2Biogen Idec, Inc., Cambridge, MA, USAAbstract: Natalizumab is an α4-integrin antagonist approved as monotherapy for patients with relapsing multiple sclerosis (MS), based on demonstrated efficacy in the pivotal AFFIRM study (N = 942). Natalizumab monotherapy reduced risk of disability progression by 42%–54% and annualized relapse rate by 68% during a period of 2 years. Natalizumab was a...

  3. Estimating Typical Multiple Sclerosis Disability Progression Speed from Clinical Observations

    OpenAIRE

    Brown, Murray G.; Mark Asbridge; Vern Hicks; Sarah Kirby; Murray, Thomas J.; Pantelis Andreou; Dong Lin

    2014-01-01

    INTRODUCTION: Multiple sclerosis (MS) is a chronic disease of the central nervous system. Estimates of MS natural history (NH) disability progression speed from clinical observations vary worldwide. This may reflect, in part, variance in censoring-bias) (missing observations) and assumptions about when irreversible disability progression events occurred. We test whether estimates of progression speed which assume midpoint survival time at irreversible disability endpoints are significantly fa...

  4. Spinal segmental myoclonus as an unusual presentation of multiple sclerosis

    OpenAIRE

    Alroughani, Raed Abdullah; Ahmed, Samar Farouk; Khan, Riyadh Ahmed; Al-Hashel, Jasem Yousef

    2015-01-01

    Background Unusual presentations of multiple sclerosis (MS) at onset may post a diagnostic dilemma to the treating neurologists. Spinal myoclonus is rare in MS and may lead to perform extensive investigations to rule out other etiologies affecting the spinal cord. Case presentation We described a 31-year-old male who presented with involuntary brief jerky movements of the left shoulder and arm with significant wasting of shoulder muscles. In retrospect, the patient had a progressive right leg...

  5. Is the frequency of multiple sclerosis increasing in Mexico?

    Science.gov (United States)

    Gonzalez, O; Sotelo, J

    1995-11-01

    Multiple sclerosis has steadily increased in Mexican mestizos from an apparently rare disorder in the 1970s to the second most frequent cause of admission to a neurology ward in the 1990s. Most patients belonged to high socioeconomic and educational groups. Familial incidence was low. Age at onset was younger than in other series and long term disability was milder than in patients from countries in which the disease is apparently more prevalent.

  6. Disability outcome measures in multiple sclerosis clinical trials

    DEFF Research Database (Denmark)

    Cohen, Jeffrey A; Reingold, Stephen C; Polman, Chris H;

    2012-01-01

    recommend practical refinements. Conversely, although substantial data support the multiple sclerosis functional composite as an alternative measure, changes to its component tests and scoring method are needed. Novel approaches, including the use of composite endpoints, patient-reported outcomes......, and measurement of biomarkers, show promise as adjuncts to the current disability measures, but are insufficiently validated to serve as substitutes. A collaborative approach that involves academic experts, regulators, industry representitives, and funding agencies is needed to most effectively develop disability...

  7. Relevance of anti-myelin antibodies in Multiple Sclerosis

    OpenAIRE

    2005-01-01

    Antibodies directed against myelin antigens have been described in multiple sclerosis (MS). Although anti-myelin antibodies have been implicated in central nervous system (CNS) demyelination, it is unclear to what extent anti-myelin antibodies contribute to MS pathogenesis. In this dissertation, the role of antibodies in MS and in the animal model experimental allergic encephalomyelitis (EAE) is addressed in eight chapters: Chapter 1: A review on antibodies, complement and Fc receptors in MS ...

  8. The Latest Innovations in the Drug Pipeline for Multiple Sclerosis

    OpenAIRE

    Radick, Lea; Mehr, Stanton R.

    2015-01-01

    Several new medications are being investigated in late-phase studies for the treatment of patients with relapsing or progressive multiple sclerosis (MS). These agents represent a variety of mechanisms of action and provide not only lower relapse rates but also improvement in disabilities. The majority of investigational trials involve selective sphingosine-1-phosphate receptor 1 immunomodulators, such as laquinimod, ozanimod, ponesimod, and siponimod, in an effort to build on the success of f...

  9. Application of diffusion tensor imaging in multiple sclerosis

    OpenAIRE

    Sousa, Filipa Costa

    2015-01-01

    Trabalho final de mestrado integrado em Medicina, apresentado à Faculdade de Medicina da Universidade de Coimbra. Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS), being a significant cause of disability. During the last years, diffusion tensor imaging (DTI) has been applied in the study of MS patients in an attempt to improve the understanding of the pathologic process at a microstructural level, in early stages of the disease. DTI, due to its high sen...

  10. Recent advances in the neuropathology of multiple sclerosis.

    Science.gov (United States)

    Stadelmann, C

    2007-06-01

    Important insights from multiple sclerosis (MS) pathology have broadened our view of the disease during the last years. Details of the inflammatory response as well as mechanisms of demyelination were elucidated. Damage to neuronal processes was identified as the major predictor of persistent disability in MS patients. Abortive repair mechanisms are increasingly studied, and our increased understanding will pave the way to new therapeutic strategies. This overview highlights some of the current views on MS pathogenesis derived from human neuropathology.

  11. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond

    OpenAIRE

    2015-01-01

    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 us...

  12. Towards immunotherapeutic drugs and vaccines against multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Maria Katsara; John Matsoukas; George Deraos; Vasso Apostolopoulos

    2008-01-01

    Multiple sclerosis (MS) is an autoimmune,demyelinating disease of the central nervous system.Numerous treatment options are available to MS patients;however,these options need to be improved.Herein,we review the current drugs and therapeutic approaches available to MS patients,preclinical trial interventions and recent animal model studies for the potential therapy of MS.Since the current treatment of MS remains elusive and is limited,animal studies and clinical research offers an optimistic outlook.

  13. Low and high CD8 positive T cells in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Maryam Izad

    2013-09-01

    Full Text Available Cumulating evidence points to a key role for CD8+ T cells in the pathogenesis of multiple sclerosis.CD8 expression level was believed to be present constantly on the surface of human peripheral blood T cells. However, it was shown that peripheral blood lymphocytes may be divided by the level of CD8 expression, into CD8+high and CD8+low T cells. Now it is well established that the CD8low population of CD8+ T cells demonstrates an activated effector phenotype while the CD8+high T cells have been reported to have regulatory function. In this report we used a flow cytometric assay to compare the frequency of these two subsets in multiple sclerosis patients (n=31 with healthy age- and gender-matched controls (n=18. We found that CD8+ T cells and CD8+low T cells significantly increased in secondary progressive (SP and primary progressive multiple sclerosis (PPMS patients in comparison to controls (p<0.0002 and p<0.004 respectively and also RRMS (p<0.005 and p<0.017 respectively. These results demonstrated the role of CD8low T cells in progressive form of multiple sclerosis.

  14. Inflammation, Iron, Energy Failure, and Oxidative Stress in the Pathogenesis of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lukas Haider

    2015-01-01

    Full Text Available Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Different trigger pathologies have been suggested by the primary cytodegenerative “inside-out” and primary inflammation-driven “outside-in” hypotheses. Recent data indicate that mitochondrial injury and subsequent energy failure are key factors in the induction of demyelination and neurodegeneration. The brain weighs only a few percent of the body mass but accounts for approximately 20% of the total basal oxygen consumption of mitochondria. Oxidative stress induces mitochondrial injury in patients with multiple sclerosis and energy failure in the central nervous system of susceptible individuals. The interconnected mechanisms responsible for free radical production in patients with multiple sclerosis are as follows: (i inflammation-induced production of free radicals by activated immune cells, (ii liberation of iron from the myelin sheets during demyelination, and (iii mitochondrial injury and thus energy failure-related free radical production. In the present review, the different sources of oxidative stress and their relationships to patients with multiple sclerosis considering tissue injury mechanisms and clinical aspects have been discussed.

  15. Change in disability profile and quality of life in multiple sclerosis patients : a five-year longitudinal study using the Multiple Sclerosis Impact Profile (MSIP)

    NARCIS (Netherlands)

    Wynia, K.; van Wijlen, A. T.; Middel, B.; Reijneveld, S. A.; Meilof, J. F.

    2012-01-01

    Background: Evidence on the progress of disease severity in Multiple Sclerosis (MS) is generally limited in scope. Objectives: To examine the course of a broad spectrum of MS-related disabilities and quality of life (QOL) in relation to disease severity, and responsiveness of the Multiple Sclerosis

  16. Neuroprotection in a novel mouse model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Katie Lidster

    Full Text Available Multiple sclerosis is an immune-mediated, demyelinating and neurodegenerative disease that currently lacks any neuroprotective treatments. Innovative neuroprotective trial designs are required to hasten the translational process of drug development. An ideal target to monitor the efficacy of strategies aimed at treating multiple sclerosis is the visual system, which is the most accessible part of the human central nervous system. A novel C57BL/6 mouse line was generated that expressed transgenes for a myelin oligodendrocyte glycoprotein-specific T cell receptor and a retinal ganglion cell restricted-Thy1 promoter-controlled cyan fluorescent protein. This model develops spontaneous or induced optic neuritis, in the absence of paralytic disease normally associated with most rodent autoimmune models of multiple sclerosis. Demyelination and neurodegeneration could be monitored longitudinally in the living animal using electrophysiology, visual sensitivity, confocal scanning laser ophthalmoscopy and optical coherence tomography all of which are relevant to human trials. This model offers many advantages, from a 3Rs, economic and scientific perspective, over classical experimental autoimmune encephalomyelitis models that are associated with substantial suffering of animals. Optic neuritis in this model led to inflammatory damage of axons in the optic nerve and subsequent loss of retinal ganglion cells in the retina. This was inhibited by the systemic administration of a sodium channel blocker (oxcarbazepine or intraocular treatment with siRNA targeting caspase-2. These novel approaches have relevance to the future treatment of neurodegeneration of MS, which has so far evaded treatment.

  17. Meningeal and cortical grey matter pathology in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Gh Popescu Bogdan F

    2012-03-01

    Full Text Available Abstract Although historically considered a disease primarily affecting the white matter of the central nervous system, recent pathological and imaging studies have established that cortical demyelination is common in multiple sclerosis and more extensive than previously appreciated. Subpial, intracortical and leukocortical lesions are the three cortical lesion types described in the cerebral and cerebellar cortices of patients with multiple sclerosis. Cortical demyelination may be the pathological substrate of progression, and an important pathologic correlate of irreversible disability, epilepsy and cognitive impairment. Cortical lesions of chronic progressive multiple sclerosis patients are characterized by a dominant effector cell population of microglia, by the absence of macrophagic and leukocytic inflammatory infiltrates, and may be driven in part by organized meningeal inflammatory infiltrates. Cortical demyelination is also present and common in early MS, is topographically associated with prominent meningeal inflammation and may even precede the appearance of classic white matter plaques in some MS patients. However, the pathology of early cortical lesions is different than that of chronic MS in the sense that early cortical lesions are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.

  18. Serum Homocysteine level in patients with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    F Ashtari

    2005-09-01

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

  19. Role of statins in the treatment of multiple sclerosis.

    Science.gov (United States)

    Ciurleo, Rosella; Bramanti, Placido; Marino, Silvia

    2014-09-01

    Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase are widely prescribed for hypercholesterolemia treatment. In the last years, statins have also been shown to exert immunomodulatory and anti-inflammatory effects which appear to be related to inhibition of isoprenylation of small GTP-binding proteins and, at least in part, independent of their cholesterol-lowering effects. These "pleiotropic" effects make statins an attractive treatment option for immune-mediated disorders such as multiple sclerosis. Studies in vitro and in experimental autoimmune encephalomyelitis animal model seem to support not only the efficacy of statins as immunomodulatory agents but also their potential neuroprotective properties, although the exact mechanism with which statins exert these effects has not yet been fully understood. The immunomodulatory, anti-inflammatory and neuroprotective properties of statins provided the incentive for several clinical trials in multiple sclerosis, in which they were tested not only as mono-therapy but also in combination with interferon-β. However, the attempt to translate the results of animal model studies in humans produced conflicting results. Further large, prospective, randomized, double-blind, placebo-controlled trials, designed to evaluate the long-term effects of statins alone or in add-on to other disease-modifying therapies, are needed to support their routine clinical use in multiple sclerosis.

  20. A high-density screen for linkage in multiple sclerosis.

    Science.gov (United States)

    Sawcer, Stephen; Ban, Maria; Maranian, Mel; Yeo, Tai Wai; Compston, Alastair; Kirby, Andrew; Daly, Mark J; De Jager, Philip L; Walsh, Emily; Lander, Eric S; Rioux, John D; Hafler, David A; Ivinson, Adrian; Rimmler, Jacqueline; Gregory, Simon G; Schmidt, Silke; Pericak-Vance, Margaret A; Akesson, Eva; Hillert, Jan; Datta, Pameli; Oturai, Annette; Ryder, Lars P; Harbo, Hanne F; Spurkland, Anne; Myhr, Kjell-Morten; Laaksonen, Mikko; Booth, David; Heard, Robert; Stewart, Graeme; Lincoln, Robin; Barcellos, Lisa F; Hauser, Stephen L; Oksenberg, Jorge R; Kenealy, Shannon J; Haines, Jonathan L

    2005-09-01

    To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

  1. Optimal management of multiple sclerosis during pregnancy: current perspectives

    Directory of Open Access Journals (Sweden)

    Borisow N

    2014-08-01

    Full Text Available Nadja Borisow, Friedemann Paul, Jan DörrNeuroCure Clinical Research Center and Clinical and Experimental Research Center for Multiple Sclerosis, Charité – Universitätsmedizin Berlin, Berlin, GermanyAbstract: Multiple sclerosis (MS is a common inflammatory demyelinating disorder of the central nervous system. It frequently affects females in their reproductive phase of life. Therefore, family planning, pregnancy, and breastfeeding are important issues in the management of MS, particularly with respect to counseling and drug treatment. This paper reviews currently available data on the outcome of pregnancies in MS patients and the influence of pregnancy on the course of the disease. We give an update on the use of various disease-modifying MS drugs during pregnancy and breastfeeding. In addition to established therapies such as interferon-β, glatiramer acetate, natalizumab, and fingolimod, we also discuss the state of knowledge about new agents such as dimethyl fumarate, teriflunomide, and alemtuzumab in the context of pregnancy and breastfeeding.Keywords: multiple sclerosis, pregnancy, lactation, disease-modifying therapy

  2. Role of autophagy in the pathogenesis of multiple sclerosis.

    Science.gov (United States)

    Liang, Peizhou; Le, Weidong

    2015-08-01

    Autophagy plays an important role in maintaining the cellular homeostasis. One of its functions is to degrade unnecessary organelles and proteins for energy recycling or amino-acids for cell survival. Ablation of autophagy leads to neurodegeneration. Multiple sclerosis (MS), a permanent neurological impairment typical of chronic inflammatory demyelinating disorder, is an auto-immune disease of the central nervous system (CNS). Autophagy is tightly linked to the innate and adaptive immune systems during the autoimmune process, and several studies have shown that autophagy directly participates in the progress of MS or experimental autoimmune encephalomyelitis (EAE, a mouse model of MS). Dysfunction of mitochondria that intensively influences the autophagy pathway is one of the important factors in the pathogenesis of MS. Autophagy-related gene (ATG) 5 and immune-related GTPase M (IRGM) 1 are increased, while ATG16L2 is decreased, in T-cells in EAE and active relapsing-remitting MS brains. Administration of rapamycin, an inhibitor of mammalian target of rapamycin ( mTOR), ameliorates relapsing-remitting EAE. Inflammation and oxidative stress are increased in MS lesions and EAE, but Lamp2 and the LC3-II/LC3-I ratio are decreased. Furthermore, autophagy in various glial cells plays important roles in regulating neuro-inflammation in the CNS, implying potential roles in MS. In this review, we discuss the role of autophagy in the peripheral immune system and the CNS in neuroinflammation associated with the pathogenesis of MS.

  3. Obesity and brain inflammation: a focus on multiple sclerosis.

    Science.gov (United States)

    Palavra, F; Almeida, L; Ambrósio, A F; Reis, F

    2016-03-01

    The increase in prevalence of obesity in industrialized societies is an indisputable fact. However, the apparent passive role played by adipocytes, in pathophysiological terms, has been gradually substituted by a metabolically active performance, relevant to many biochemical mechanisms that may contribute to a chronic low-grade inflammatory status, which increasingly imposes itself as a key feature of obesity. This chronic inflammatory status will have to be integrated into the complex equation of many diseases in which inflammation plays a crucial role. Multiple sclerosis (MS) is a chronic inflammatory condition typically confined to the central nervous system, and many work has been produced to find possible points of contact between the biology of this immune-mediated disease and obesity. So far, clinical data are not conclusive, but many biochemical features have been recently disclosed. Brain inflammation has been implicated in some of the mechanisms that lead to obesity, which has also been recognized as an important player in inducing some degree of immune dysfunction. In this review, we collected evidence that allows establishing bridges between obesity and MS. After considering epidemiological controversies, we will focus on possible shared mechanisms, as well as on the potential contributions that disease-modifying drugs may have on this apparent relationship of mutual interference.

  4. 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.

  5. The meninges: new therapeutic targets for multiple sclerosis.

    Science.gov (United States)

    Russi, Abigail E; Brown, Melissa A

    2015-02-01

    The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments.

  6. A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica.

    Science.gov (United States)

    Gebregiworgis, Teklab; Nielsen, Helle H; Massilamany, Chandirasegaran; Gangaplara, Arunakumar; Reddy, Jay; Illes, Zsolt; Powers, Robert

    2016-02-05

    Urine is a metabolite-rich biofluid that reflects the body's effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum disorder (NMO-SD) patients and analyzed with NMR, multivariate statistics, one-way ANOVA, and univariate statistics. Urine from MS patients exhibited a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid cycle, and glycolysis. Metabolites altered in urine from MS patients were shown to be related to known pathogenic processes relevant to MS, including alterations in energy and fatty acid metabolism, mitochondrial activity, and the gut microbiota.

  7. Management of pain in multiple sclerosis: a pharmacological approach.

    Science.gov (United States)

    Solaro, Claudio; Uccelli, Michele Messmer

    2011-08-16

    About half of patients with multiple sclerosis (MS) report pain; treatment for pain alone accounts for nearly 30% of the total use of medications for the management of all MS-related symptoms. Patients with MS can experience more than one type of pain simultaneously and at any point during the disease course, even in newly or recently diagnosed cases. Pain in MS can be associated with other symptoms, including spasticity, fatigue and mood disorder. Pain sufferers experience disruption in daily life activities, work, mood, recreation and general enjoyment of life, and report low satisfaction with pain management. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. The majority of clinical evidence regarding treatment stems from small pilot and open-label studies; therefore, treatment of pain associated with MS is often based on anecdotal reports and clinicians' experience. The open-label design of the majority of studies, the unavailability of large samples and the difficulty of performing placebo-controlled studies because of ethical considerations result in insufficient evidence to support or refute the effectiveness of pain medications. This Review presents available data regarding pharmacological approaches for addressing pain in MS and highlights the shortcomings in pain management research.

  8. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond.

    Science.gov (United States)

    Ruck, Tobias; Bittner, Stefan; Wiendl, Heinz; Meuth, Sven G

    2015-07-20

    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.

  9. Infection risk in patients on multiple sclerosis therapeutics.

    Science.gov (United States)

    Williamson, Eric M; Berger, Joseph R

    2015-03-01

    The interface of multiple sclerosis (MS) and infection occurs on several levels. First, infectious disease has been postulated as a potential trigger, if not cause, of MS. Second, exacerbation of MS has been well-documented as a consequence of infection, and, lastly, infectious diseases have been recognized as a complication of the therapies currently employed in the treatment of MS. MS is a disease in which immune dysregulation is a key component. Examination of central nervous system (CNS) tissue of people affected by MS demonstrates immune cell infiltration, activation and inflammation. Therapies that alter the immune response have demonstrated efficacy in reducing relapse rates and evidence of brain inflammation on magnetic resonance imaging (MRI). Despite the altered immune response in MS, there is a lack of evidence that these patients are at increased risk of infectious disease in the absence of treatment or debility. Links between infections and disease-modifying therapies (DMTs) used in MS will be discussed in this review, as well as estimates of occurrence and ways to potentially minimize these risks. We address infection in MS in a comprehensive fashion, including (1) the impact of infections on relapse rates in patients with MS; (2) a review of available infection data from pivotal trials and postmarketing studies for the approved and experimental DMTs, including frequency, types and severity of infections; and (3) relevant risk minimization strategies, particularly as they pertain to progressive multifocal leukoencephalopathy (PML).

  10. Novel therapeutics in multiple sclerosis management: clinical applications.

    Science.gov (United States)

    Leist, Thomas; Hunter, Samuel F; Kantor, Daniel; Markowitz, Clyde

    2014-01-01

    Multiple sclerosis (MS) affects an estimated 300,000 individuals in the United States. No cure exists and although there is a lack of consensus on management, strategies to modify disease course are available. These strategies involve initiating disease-modifying therapies that have been found to slow disease progression and prevent disability symptoms, thereby improving function for MS patients. The overall goal of early disease management is to intervene prior to irreversible neuronal destruction in order to delay disability progression and improve quality of life. Maintaining a lower level of disability for a longer period of time postpones and ultimately attempts to prevent reaching a level of immobility and irreversible disability. However, due to the complex nature of disease and its unique, individual patient course, no patient can be treated alike and no patient responds to therapy similarly. Therefore, MS research is continuous in its evolution of therapeutic development, focusing on neuroprotective effects and agents with distinctive mechanisms of action allowing for unique safety and efficacy profiles. Investigations include novel oral agents and monoclonal antibodies. Many of the approved agents also are continually being investigated in order to evaluate comparative data, the most appropriate means of implementing subsequent therapy upon failure, responsiveness to therapeutic agent when switched, and long-term safety and efficacy. This multimedia webcast educational activity will cover the current state of MS science, current therapies in MS, emerging treatments in clinical trials for MS as well as differences between physicians in diagnosis and management of MS and their evolving practices.

  11. Automated detection of multiple sclerosis lesions in serial brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Llado, Xavier; Ganiler, Onur; Oliver, Arnau; Marti, Robert; Freixenet, Jordi [University of Girona, Computer Vision and Robotics Group, Girona (Spain); Valls, Laia [Dr. Josep Trueta University Hospital, Department of Radiology, Girona (Spain); Vilanova, Joan C. [Girona Magnetic Resonance Center, Girona (Spain); Ramio-Torrenta, Lluis [Dr. Josep Trueta University Hospital, Institut d' Investigacio Biomedica de Girona, Multiple Sclerosis and Neuroimmunology Unit, Girona (Spain); Rovira, Alex [Vall d' Hebron University Hospital, Magnetic Resonance Unit, Department of Radiology, Barcelona (Spain)

    2012-08-15

    Multiple sclerosis (MS) is a serious disease typically occurring in the brain whose diagnosis and efficacy of treatment monitoring are vital. Magnetic resonance imaging (MRI) is frequently used in serial brain imaging due to the rich and detailed information provided. Time-series analysis of images is widely used for MS diagnosis and patient follow-up. However, conventional manual methods are time-consuming, subjective, and error-prone. Thus, the development of automated techniques for the detection and quantification of MS lesions is a major challenge. This paper presents an up-to-date review of the approaches which deal with the time-series analysis of brain MRI for detecting active MS lesions and quantifying lesion load change. We provide a comprehensive reference source for researchers in which several approaches to change detection and quantification of MS lesions are investigated and classified. We also analyze the results provided by the approaches, discuss open problems, and point out possible future trends. Lesion detection approaches are required for the detection of static lesions and for diagnostic purposes, while either quantification of detected lesions or change detection algorithms are needed to follow up MS patients. However, there is not yet a single approach that can emerge as a standard for the clinical practice, automatically providing an accurate MS lesion evolution quantification. Future trends will focus on combining the lesion detection in single studies with the analysis of the change detection in serial MRI. (orig.)

  12. Body composition and physical function in women with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Christie L. Ward, MS

    2013-11-01

    Full Text Available Persons with multiple sclerosis (MS have reduced physical activity (PA and lower-limb physical function and potentially disordered body composition compared with their peers without MS. The aim of this study was to determine whether PA and body composition were differentially associated with lower-limb physical function in persons with MS compared with controls. Females with MS and age- and body mass index-matched female controls (n = 51; average age 48.1 +/– 9.7 yr were measured for PA with daily step counts, relative fat mass (%Fat, and leg lean mass (LM-LEG via dual energy X-ray absorptiometry and for lower-limb physical function with objective performance tests. Persons with MS had 12.5% to 53% poorer lower-limb physical function than controls (all p < 0.05. PA, %Fat, and LM-LEG to body mass ratio (LM-LEG/BM were associated with lower-limb physical function in both persons with MS and controls (all p < 0.05. Based on median splits, higher %Fat, lower LM-LEG/BM, and MS conferred poorer lower-limb physical function (all p < 0.05. PA, %Fat, and LM-LEG/BM were associated with lower-limb physical function, suggesting that body composition, specifically reducing adiposity and increasing lean mass and/or increasing PA levels, may be a potential target for MS interventions.

  13. Concomitant amyotrophic lateral sclerosis and paraclinical laboratory features of multiple sclerosis: coincidence or causal relationship?

    Science.gov (United States)

    Borisow, Nadja; Meyer, Thomas; Paul, Friedemann

    2013-01-23

    We report a 55-year-old patient, presenting with paresis, muscle atrophy and dysarthria, all symptoms accordable to definite amyotrophic lateral sclerosis (ALS). However, MRI and cerebrospinal fluid show abnormalities typical of multiple sclerosis (MS). On the basis of this case report, we discuss possible overlaps between both diseases by comparing clinical and paraclinical features including laboratory, radiological and electrophysiological diagnostics. As genetic, as well as environmental, factors are assumed to be involved in the development of both the diseases, literature is reviewed according to similar cases, results of autopsies and possible parallels in pathogenesis. In summary, based on the data currently available, the hypothesis of ALS being a neurodegenerative multisystem disorder, a common pathophysiological pathway or, alternatively, a random comorbidity of ALS and MS in this patient has to be discussed.

  14. Challenges in randomized controlled trials and emerging multiple sclerosis therapeutics.

    Science.gov (United States)

    Huang, DeRen

    2015-12-01

    The remarkable global development of disease-modifying therapies (DMTs) specific for multiple sclerosis (MS) has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials (RCTs) for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica (NMO) and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.

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

    OpenAIRE

    Visser LH; Heerings MA; Jongen PJ; van der Hiele K

    2016-01-01

    Leo H Visser,1,2 Marco A Heerings,3 Peter J Jongen,4,5 Karin van der Hiele1,3,6 1Department of Neurology, Elisabeth-TweeSteden Hospital, Tilburg, 2Ethics of Care, University of Humanistic Studies, Utrecht, 3National Multiple Sclerosis Foundation, Rotterdam, 4Department of Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, Groningen, 5MS4 Research Institute, Nijmegen, 6Section Health, Medical and Neuropsychology, Department of Psychology, Leiden...

  16. [Multiple sclerosis in literature, cinema and television].

    Science.gov (United States)

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

    2016-12-16

    Introduccion. En la actualidad, la atencion del paciente con esclerosis multiple y su entorno supone un reto clinico y terapeutico para los profesionales de la salud. El objetivo del presente trabajo es analizar la aparicion de la esclerosis multiple en la literatura, el cine y la television, y reflexionar sobre su imagen en dichos medios. Desarrollo. Se han revisado algunas obras representativas que han abordado la esclerosis multiple, y se ha observado que en muchas de ellas se ofrece una vision muy fidedigna de la enfermedad. Del mismo modo, se han revisado las principales peliculas y series de television que, en ocasiones, son un reflejo cercano al publico general de la vision e impacto de la enfermedad sobre los pacientes o familiares, no exentas de excesos dramaticos y distorsiones de la realidad. Conclusiones. La literatura refleja, en gran medida, la epidemiologia real, los sintomas y la progresion de la enfermedad, mientras que las opciones diagnosticas y terapeuticas parecen estar en un segundo plano. El cine y la television han ofrecido una imagen correcta, pero en ocasiones atendiendo mas a efectos dramaticos. Es importante que la literatura, el cine y la television ofrezcan una vision ajustada a la realidad de esta enfermedad para dar a conocer esta afeccion neurologica y contribuir a disminuir su estigma.

  17. Neural drive increases following resistance training in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Dalgas, Ulrik; Stenager, Egon; Lund, Charlote Caroline;

    2013-01-01

    The present study tested the hypothesis that lower body progressive resistance training (PRT) increases the neural drive expressed as surface electromyographical (EMG) activity in patients with multiple sclerosis (MS). The study was a randomised controlled trial (RCT) including a 12-week follow u...... of the lower extremities improved the neural drive expressed as maximal surface EMG activity in patients with MS, with effects persisting 12 weeks after the intervention. The study was registered at clinicalTrials.gov, Protocol no. NCT00381576....

  18. Outcome Measures in Clinical Trials for Multiple Sclerosis.

    Science.gov (United States)

    van Munster, Caspar E P; Uitdehaag, Bernard M J

    2017-02-09

    Due to the heterogeneous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. Therefore, it can be difficult to assess the true efficacy of interventions in clinical trials. In phase III trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale and the relapse rate. Secondary outcome measures in these trials are the number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) of the brain. These secondary outcome measures are often primary outcome measures in phase II trials in MS. Despite several limitations, the traditional clinical measures are still the mainstay for assessing treatment efficacy. Newer and potentially valuable outcome measures increasingly used or explored in MS trials are, clinically, the MS Functional Composite and patient-reported outcome measures, and on MRI, brain atrophy and the formation of persisting black holes. Several limitations of these measures have been addressed and further improvements will probably be proposed. Major improvements are the coverage of additional functional domains such as cognitive functioning and assessment of the ability to carry out activities of daily living. The development of multidimensional measures is promising because these measures have the potential to cover the full extent of MS activity and progression. In this review, we provide an overview of the historical background and recent developments of outcome measures in MS trials. We discuss the advantages and limitations of various measures, including newer assessments such as optical coherence tomography, biomarkers in body fluids and the concept of 'no evidence of disease activity'.

  19. Increased expression of cystine/glutamate antiporter in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Villoslada Pablo

    2011-06-01

    Full Text Available Abstract Background Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS. Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter xc-, an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system xc- in glutamate homeostasis alterations in MS pathology. Methods Primary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE, the animal model of MS, and in samples of MS patients. Results and discussion We show here that human activated monocytes release glutamate through cystine/glutamate antiporter xc- and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes. Conclusions Together, these results reveal that increased expression of the cystine/glutamate antiporter system xc- in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.

  20. [Affective and psychotic disorders in multiple sclerosis].

    Science.gov (United States)

    Pozuelo-Moyano, Beatriz; Benito-León, Julián

    2015-12-01

    Introduccion. La esclerosis multiple (EM) es la segunda causa mas importante de discapacidad de origen neurologico en los adultos jovenes. Tanto la sintomatologia fisica como la psiquiatrica (trastornos afectivos y psicoticos) impactan de manera negativa en la calidad de vida relacionada con la salud de los pacientes con EM. Objetivo. Elucidar de modo critico la prevalencia y la patogenia de los sintomas afectivos y psicoticos presentes en la EM. Desarrollo. Se incluye una actualizacion de los estudios publicados mas significativos que han analizado la prevalencia y la patogenia de la sintomatologia afectiva y psicotica en los pacientes con EM. Para explorar la asociacion entre los sintomas afectivos y psicoticos con la EM se ha revisado la evidencia disponible hasta el momento. Conclusiones. La depresion es el trastorno psiquiatrico mas frecuente en la EM. Es necesaria mas investigacion para elucidar los mecanismos subyacentes que pueden provocar sintomas afectivos y psicoticos en la EM. El control de dichos sintomas en los pacientes de EM podria mejorar su calidad de vida relacionada con la salud.