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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
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
- 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
► Caucasian
► 2-3 times more common in women
 Incidence of MS in 1st degree relative 20 times higher
vs. general population
Rose AS. Multiple sclerosis: an overview. Adv Neurol 1981;31:3-9.
World Map of MS
► 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
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
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
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
► 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
 irreversable
 MS progression
► N-acetylaspartate
 AA critical for axonal health
 undergoes dramatic/ destructive changes
► MS
affects more of the brain than previously
Periventricular MS lesions
-Clinical History:
This is a 39-year-old WF with
15 year history MS 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
► 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 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 – National MS Society
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
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
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?