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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 ► 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 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. World Map of MS http://www.themcfox.com/multiple-sclerosis/ms-world-map/world-map-of-ms.htm 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 Signs and Symptoms ► 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 McFarlin DE, McFarland HF. Multiple sclerosis. N Engl J Med 1982;307(19):1183-8 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 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 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 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 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 Periventricular MS lesions -Clinical History: This is a 39-year-old WF with 15 year history MS http://www.uhrad.com/ mriarc/mri007a.jpg 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 Pharmacotherapy for MS ► Modify ► Treat disease course (eg: Avonex ) ® exaccerbations (eg: corticosteroids) ► Manage symptoms (eg: B/B with propantheline) ► Improve function and saftey (eg: PT, OT) Pharmacotherapy for MS Disease Modifying Agents ► Interferon β-1a (Avonex , Rebif ) ► Interferon β-1b (Betaseron ) ► Glatiramer acetate (Copaxone ) ® ® ® ► Mitoxantrone ® (Novantrone ) ® 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 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) 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):28997. 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 Thank you ► Questions, no questions?