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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?