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Multiple Sclerosis: A Disease Update

Multiple Sclerosis: A Disease Update. Spring 2006 PAS 646 Masters Project. Kevin M. Schuer UK College of Health Sciences Physician Assistant Program. Background. Multiple sclerosis (MS) is a chronic, long-term condition that affects the central nervous system. MS is an autoimmune disease

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Multiple Sclerosis: A Disease Update

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  1. Multiple Sclerosis: A Disease Update Spring 2006 PAS 646 Masters Project Kevin M. Schuer UK College of Health Sciences Physician Assistant Program

  2. Background • Multiple sclerosis (MS) is a chronic, long-term condition that affects the central nervous system. • MS is an autoimmune disease • Infectious, Environmental, Genetic etiology? • MS affects over 400,000 people in the US, and may affect 2.4 million people worldwide -http://www.msactivesource.com/ 2005

  3. Epidemiology of MS • Difficult to diagnose • Prevalence: 4/100,000 • Most diagnosed between 20 and 50 y/o • 70% manifest Sx between 21-40 y/o • Northern Latitudes • Caucasian • 2-3 times more common in women • Incidence of MS in 1st degree relative 20 times higher vs. general population http://www.nationalmssociety.org/Sourcebook-Epidemiology Rose AS. Multiple sclerosis: an overview. Adv Neurol 1981;31:3-9.

  4. World Map of MS http://www.themcfox.com/multiple-sclerosis/ms-world-map/world-map-of-ms.htm

  5. Background Wide range of symptoms Often Seldom Inflammation and Demyelination in the CNS Myelin is lost in multiple areas, leaving scar tissue called plaques or sclerosis Different for each individual -http://healthyliving.org

  6. Optic Neuritis Arm and leg weakness Sense of touch Pain Bowel/ Bladder Balance/ Coordination Fatigue Cognitive function Mood changes Sexual Dysfunction Spasticity/ Numbness Diagnosed between the ages of 20 and 50 W>M (2-3X) Northern European ancestry (mainly) Asian, African, and Hispanic ancestry not immune Signs and Symptoms McFarlin DE, McFarland HF. Multiple sclerosis. N Engl J Med 1982;307(19):1183-8

  7. Clinical Courses of MS • Relapsing-Remitting • Primary-Progressive • Secondary-Progressive • Progressive-Relapsing Polman CH, Wolinsky JS, Reingold SC. Multiple sclerosis diagnostic criteria: three years later. Mult Scler 2005;11(1):5-12

  8. Pathophysiology of MS • The classical demyelinating disease of the CNS • Damage to the myelin and oligodendrocytes • Cell death by either apoptosis or necrosis • Macrophages and microglia participate in the process of demyelination Rose AS. Multiple sclerosis: an overview. Adv Neurol 1981;31:3-9

  9. Immunology of MS • Error in the ‘education’ of T-cells, which makes them unable to distinguish self from non-self • Mis-educated T-cells mistake the body's own myelin as a foreign antigen • Cascade of immune events, including: • the release of B-lymphocytes • activated B cells manufacture auto-antibody • cytokine release- TNF, IL-12, and IFNg • This inflammatory process is non self-limiting • the process persists • damage occurs in the surrounding tissues http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.immunol.23.021704.115707

  10. Pathophysiology of MS • Infiltration of T-cells in the perivascular spaces and the surrounding parenchyma of the brain • Cell adhesion allowing the infiltration of lymphocytes / mononuclear cells into the CNS • Generation of potentially damaging cytokines and toxic molecules within the white matter Trapp BD. Pathogenesis of multiple sclerosis: the eyes only see what the mind is prepared to comprehend. Ann Neurol 2004;55(4):455-7

  11. Pathophysiology of MS • Axonal destruction • irreversable • MS progression • N-acetylaspartate • AA critical for axonal health • undergoes dramatic/ destructive changes • MS affects more of the brain than previously thought

  12. Periventricular MS lesions -Clinical History: This is a 39-year-old WF with 15 year history MS http://www.uhrad.com/ mriarc/mri007a.jpg

  13. Diagnosing MS • Complete Medical History • Nervous System Functioning • Diagnostic Tests • MRI, EVP’s, LP • Two Basic Signs are Required to Confirm MS 1. Signs of Dx in different parts of the CNS 2. Evidence of two separate exaccerbations of Dx Multiple Sclerosis: Diagnosis, Medical Management, and Rehabilitation (Jack S. Burks, MD and Kenneth P. Johnson, MD, Editors), Demos Medical Publishing, 2000

  14. Pharmacotherapy for MS • Modify disease course (eg: Avonex®) • Treat exaccerbations (eg: corticosteroids) • Manage symptoms (eg: B/B with propantheline) • Improve function and saftey (eg: PT, OT)

  15. Pharmacotherapy for MSDisease Modifying Agents • Interferon β-1a (Avonex®, Rebif®) • Interferon β-1b (Betaseron®) • Glatiramer acetate (Copaxone®) • Mitoxantrone (Novantrone®)

  16. Research/ Clinical Trials • Tysabri (natalizumab), 2003 • Olig-1 gene • Migration studies (West Indies study) • Lipitor® and MS • MS and EBV, Stress, etc. • MS and stem cell therapy • MS and vitamin D • Many new agents in clinical trials http://www.nmss.org research and clinical trials

  17. Things to remember…Who gets MS? • Women • Middle-aged (30-40s) • Avg. age of onset 28 y/o • Any family Hx (autoimmune diseases) • Clumsiness* • Vision changes • Investigate (males, <30 or >40, unexplained Sx’s) • Work-up (CC, PMI, FH, PE)

  18. References/ Resources http://www.nmss.org – National MS Society 1. Noseworthy JH. Management of multiple sclerosis: current trials and future options. Curr Opin Neurol 2003;16(3):289-97. 2. Trapp BD. Pathogenesis of multiple sclerosis: the eyes only see what the mind is prepared to comprehend. Ann Neurol 2004;55(4):455-7. 3. McFarlin DE, McFarland HF. Multiple sclerosis (first of two parts). N Engl J Med 1982;307(19):1183-8. 4. Inglese M, van Waesberghe JH, Rovaris M, et al. The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS. Neurology 2003;60(5):853-60. 5. Lublin FD. The diagnosis of multiple sclerosis. Curr Opin Neurol 2002;15(3):253-6. 6. Tintore M, Rovira A, Martinez MJ, et al. Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. AJNR Am J Neuroradiol 2000;21(4):702-6. 7. Lassmann H, Raine CS, Antel J, Prineas JW. Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J Neuroimmunol 1998;86(2):213-7. 8. Young IR, Hall AS, Pallis CA, Legg NJ, Bydder GM, Steiner RE. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981;2(8255):1063-6. 9. Weinshenker BG. Epidemiology of multiple sclerosis. Neurol Clin 1996;14(2):291-308. 10. Kurtzke JF. Epidemiology of multiple sclerosis. Does this really point toward an etiology? Lectio Doctoralis. Neurol Sci 2000;21(6):383-403. 11. Elian M, Nightingale S, Dean G. Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies

  19. Questions, no questions? Thank you

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