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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

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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
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
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.

slide4

World Map of MS

http://www.themcfox.com/multiple-sclerosis/ms-world-map/world-map-of-ms.htm

background5
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

Signs and Symptoms

McFarlin DE, McFarland HF. Multiple sclerosis.

N Engl J Med 1982;307(19):1183-8

clinical courses of ms
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
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
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 ms10
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 ms11
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
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
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
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)
pharmacotherapy for ms disease modifying agents
Pharmacotherapy for MSDisease Modifying Agents
  • Interferon β-1a (Avonex®, Rebif®)
  • Interferon β-1b (Betaseron®)
  • Glatiramer acetate (Copaxone®)
  • Mitoxantrone (Novantrone®)
research clinical trials
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
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
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

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