Multiple Sclerosis:
Overview for Dentists
What does MS look like?
• Julia—a 35yo white married mother of 3 who is exhausted
all the time and can’t drive because of vision problems and
numbness in her feet
• Jackson—a 25yo African-American man who stopped
working because he can’t control his bladder or remember
what he read in the morning paper
• Maria—a 10yo Hispanic girl who falls down a lot and
whose parents just told her she has MS
• Loretta—a 47yo white single woman who moved into a
nursing home because she can no longer care
for herself
What else does MS look like?
• Sam—a 45yo divorced white man who has looked and felt
fine since he was diagnosed seven years ago
• Karen—a 24yo single white woman who is severely
depressed and worried about losing her job because of
her diagnosis of MS
• Sandra—a 30yo single mother of two who experiences
severe burning pain in her legs and feet
• Richard—who was found on autopsy at age 76 to have
MS but never knew it
• Jeannette—whose tremors are so severe that she cannot
feed herself
What MS Is:
• MS is thought to be a disease of the immune system—
possibly autoimmune.
• The primary targets of the immune attack are the myelin
coating around the nerves in the central nervous system
(CNS—brain, spinal cord, and optic nerves) and the
nerve fibers themselves.
• Its name comes from the scarring caused by
inflammatory attacks at multiple sites in the central
nervous system.
What MS Is Not:
• MS is not:
– Contagious
– Directly inherited
– Always severely disabling
– Fatal—except in fairly rare instances
• Being diagnosed with MS is not a reason to:
– Stop working
– Stop doing things that one enjoys
– Not have children
What Causes MS?
Genetic
Predisposition
Environmental
Trigger
Immune Attack
Loss of myelin
& nerve fiber
What happens in MS?
“Activated” T cells...
...cross the blood-brain barrier…
…launch attack on myelin & nerve fibers...
…to obstruct nerve signals
myelinated nerve fiber
myelinated nerve fiber
A Close Look at a Myelinated Axon
Nerve Damage and Myelin Loss
A
B
C
D
E
A. Normally, axons have a protective myelin coating that allows
conduction of electrical impulses
B. In MS, the immune system destroys myelin, resulting in slowing of
conduction and exposure of axons
C. Exposed axons may then be severed…
D. …leading to permanent loss of the axon
E. The result is permanent loss of nerve function
Adapted from Trapp BD, et al. The Neuroscientist. 1999;5:48-57.
Active Inflammatory Demyelination
and Axonal Transection
• It has been shown that
active inflammation
results in both
demyelination and
axonal transection
Arrowheads = areas of active demyelination; Arrow = terminal axon ovoid; Human brain;
Red = immunostained for myelin basic protein; Green = immunostained for nonphosphorylated neurofilament;
Bar = 45 m.
Trapp BD et al. N Engl J Med. 1998;338:278-285.
Peterson JW et al. Neurol Clin. 2005;23:107-129.
How is MS diagnosed?
• MS is a clinical diagnosis:
– Signs and symptoms
– Medical history
– Laboratory tests
• Requires dissemination in time and space:
– Space: Evidence of scarring (plaques) in at least
two separate areas of the CNS (space)
– Time: Evidence that the plaques occurred at
different points in time
• There must be no other explanation
What tests may be used to help
confirm the diagnosis?
• Magnetic resonance
imaging (MRI)
• Visual evoked potentials
(VEP)
• Lumbar puncture
Who gets MS?
• Usually diagnosed between 20 and 50
– Occasionally diagnosed in young children and older
adults
• More common in women than men (>2-3:1)
• Most common in those of Northern European ancestry
– More common in Caucasians than Hispanics or African
Americans; rare among Asians
• More common in temperate areas of the world
The genetic factor in MS
• The risk of getting MS is approximately:
– 1/750 for the general population (0.1%)
– 1/40 for person with a close relative with MS (3%)
– 1/4 for an identical twin (25%)
• 20% of people with MS have a blood relative with MS
The risk is higher in any family in which there are several
family members with the disease (multiplex families)
Clinical Patterns of MS
Relapsing-remitting
Secondary progressive
Primary progressive
Progressive relapsing
Time
Adapted from Lublin et al. Neurology. 1996;46:907-911.
Disease Courses in MS:
Demographics
(N=3019)
Primaryprogressive
10%
Progressiverelapsing
5%
Secondary-progressive
30%
Jacobs et al. Mult Scler. 1999;5:369-376
Relapsing-remitting
55%
Managing Multiple Sclerosis
•A complex disease requiring a multi-pronged approach
that involves many clinical disciplines:
– Disease Management
– Relapse Management
– Symptom Management
– Rehabilitation
– Psychosocial Support
Management of Multiple Sclerosis
The MS “Treatment Team”:
•
•
•
•
•
•
•
•
Neurologist
Urologist
Nurse
Primary care physician
Physiatrist
Physical therapist
Occupational therapist
Speech/language
pathologist
•
•
•
•
Psychiatrist
Psychotherapist
Neuropsychologist
Social worker/Care
manager
• Pharmacist
FDA-Approved Disease-Modifying Drugs
Drug
Origin
Dosage
Freq
Route
IFNb-1b
Recombinant protein
0.25 mg
Every other day
SC
IFNb-1a IM
Recombinant protein
30 mcg
1x/wk
IM
Glatiramer acetate
Random polypeptides
20 mg
Every day
SC
IFNb-1a SC
Recombinant protein
22 mcg
44 mcg
3x/wk
SC
Fingolimod
Sphingosine 1-phosphate
receptor modulator
0.5 mg
Every day
Oral
Teriflunomide
De novo pyrimidine
synthesis inhibitor of the
DHO-DH enzyme
7 mg or 14 mg
Daily
Oral
Dimethyl fumarate
Oral formulation of
dimethyl fumarate rapidly
hydrolyzed to monomethyl
fumarate
24o mg
Twice daily
Oral
Mitoxantrone
Chemotherapy
12 mg/m2
(cumulative
lifetime dose <
140 mg/m2)
Every 3 months
IV infusion
Natalizumab
Humanized Mab
300 mg
Every 4 wks
IV infusion
Managing Progressive MS
• Azathiorpine (Imuran)
• Methotrexate
• Mitoxantrone (Novantrone)
• Monthly administration of methylprednisolone
• IVIgG
• Cladribine
• Cytoxan
• Bone marrow transplantation
Relapse Management
• Relapse = new symptom or sudden worsening of old
symptom lasting at least 24 hours, and usually
accompanied by a finding
• Treatment with corticosteroids recommended if relapse
significantly interferes with everyday functioning
– 3-5 day course of high-dose intravenous methylprednisolone
with or without oral taper
– High-dose oral steroids may also be used
• Rehabilitation can help restore function following a
relapse
MS Symptom Management
• MS symptoms are variable and unpredictable
-
-
Fatigue (most common)
Decreased visual acuity,
diplopia
Bladder and/or bowel
dysfunction
Pain
Sexual dysfunction
Paresthesias (tingling,
(numbness, burning)
Emotional disturbances
(depression, mood
swings)
-
-
Cognitive difficulties
(memory, attention,
processing)
Heat sensitivity
Spasticity
Gait, balance, and
coordination problems
Speech/swallowing
problems
Tremor
Orofacial Manifestations of MS
• Intermittent facial numbness
• Facial palsy or spasm
• Paroxysmal pain syndromes (neuropathic)
– High-frequency episodes of shock-like or lancinating pain
– Trigeminal neuralgia (1-5% of patients)
• Mild dysarthria
• Lhermitte sign
• Monocular visual disturbances
Fischer DJ et al. Multiple sclerosis: an update for oral health care providers. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2009; 108:318-327.
Depression in MS:
Diagnosis and Treatment
• Symptoms of depression can be confused with
symptoms of MS  difficult to diagnose.
• Depression is under-diagnosed and under-treated
in MS.
• Best treatment for depression:
Psychotherapy + Medication (+ Exercise)
Depression in MS: What We Know
• Depression differs from normal grieving.
• People with MS are at increased risk.
• 50+% of people will experience a major depressive
episode at some point over the course of the
disease.
• Suicide is 7.5x more common in MS than in
general population (Sadovnick et al., 1991).
• Depression in MS is under diagnosed and under
treated.
Feinstein, A. (2007). The clinical neuropsychiatry of multiple sclerosis (2nd ed.). Cambridge
and New York: Cambridge University Press.
Cognitive Functions Affected in MS
•
•
•
•
•
•
Memory - acquisition and retrieval
Attention & concentration - working memory
Speed of information processing
Executive Functioning
Visual/spatial organization
Verbal fluency - word finding
DeLuca, J. What we know about cognitive changes in multiple sclerosis. In LaRocca, N &
Kalb, R (eds.) Multiple sclerosis: understanding the cognitive challenges. New York: Demos
Medical Publishing, 2006.
Cognitive Symptoms
Severity of Cognitive Changes
in Multiple Sclerosis
None
50%
Mild
40%
Moderate to
severe
10%
Cognitive Functions Unaffected in MS
•
•
•
•
•
General intellect
Long-term (remote) memory
Recognition memory
Conversational skill
Reading comprehension
Common Misconceptions about
MS and cognition
• Cognitive impairment (CI) is rare in MS.
• CI only occurs in late stage MS or severe MS.
• MS is a white-matter disease and does not affect:
1) brain volume, 2) gray matter, 3) the cerebral
cortex.
• If an MS patient can pass the mental status exam,
everything is OK.
• Memory problems reported by MS patients are
caused by stress, anxiety, and/or depression.
• Discussing CI will upset MS patients/families.
Cognition and Other Disease Characteristics
• Cognitive function correlates with lesion load and
brain atrophy.
• Cognitive dysfunction can occur at any time (even
as a first symptom) but is more common later on.
• Cognitive dysfunction can occur with any disease
course, but is more likely in progressive MS.
• Being in an exacerbation is a risk factor for
cognitive dysfunction.
• Depression can worsen cognition, particularly
executive functions (Arnett et al., 1999).
LaRocca N, Kalb R. Multiple Sclerosis: Understanding the Cognitive Challenges.
New York: Demos Medical Publishing, 2006.
MS-Related Stresses
for Patients and Families
• MS is a chronic disease that many will live with for
decades.
• The unpredictability from day to day and year to
year is difficult for patients and families to handle
• MS is a disease characterized by change and loss.
• Treatment costs and loss of income threaten
patient and family well-being.
• With more options available and choices to make,
patients and families worry about making “wrong”
choices.
Dental Management of MS Patients:
Special Considerations
•
•
•
•
•
Office accessibility
Mobility impairment (getting to appointments; transfers)
Fatigue (self-care; getting to appointments)
Weakness/incoordination (self-care)
Possible cognitive impairment (self-care; remembering
appointments, remembering instructions)
• Possible mood changes (self-care)
• Possible facial pain
• Medication side effects (xerostomia)
Commonly-Used Medications
that Cause Xerostomia
• Bladder Medications
–
–
–
–
–
–
darifenicen
oxybutynin
propantheline
solifenacin succinate
tolterodine
trospirum chloride
• Antidepressants
– amitriptyline
– duloxetine
– fluoxetine
• Antidepressants
–
–
–
–
–
–
amitriptyline
duloxetine
fluoxetine
paroxetine
sertraline
Venlafaxine
• Anti-fatigue Medication
– Amantadine
Where do we go from
here?
Current Treatment Priorities
• Better understanding of MS pathogenesis and
heterogeneity to guide development of better therapies
and monitoring methods
• Additional treatment options for relapsing-remitting MS
RRMS) that are more effective, convenient, and/or
tolerable
• Effective therapies for purely progressive MS
• Neuroprotective and repair strategies
• More effective treatments for common symptoms such
as fatigue, pain, tremor, and cognitive impairment
• More effective psychosocial suport
Cohen J. Arch Neurol. 2009;66(7):821-828
On the Horizon - Parenteral Medications
• Alemtuzumab—In phase II trial, significantly reduced the rate of
sustained disability progression vs. INF beta-1a. Also reduced
relapse rate and improved EDSS score.1 Phase III trials underway
• Daclizumab—In phase II trial, pts., adding daclizumab to INF
beta experienced a significant reduction in cumulative # of new,
enhancing lesions.2
• Rituximab—In phase II trial, reduction in GdE lesions vs. placebo
and smaller proportion of pts. experiencing relapses.3
• Dirucotide—In SPMS, Phase II trial showed trend toward slower
rate of progression—favoring HLA-DR2-positive and/or DR4-positive
pts.4
• BHT-3008—In phase II trial, GdE lesions significantly reduced vs.
placebo.5
(Cohen J. Arch Neurol 2009; 66(7):821-828)
NMSS Resources for Your Patients
• 40+ chapters around the country
• Web site (www.nationalMSsociety.org)
• Access to information, referrals, and support
(1-800-344-4867)
• Educational programs (in-person, online)
• Support programs (self-help groups, peer and
professional counseling, friendly visitors)
• Consultation (legal, employment, insurance,
long-term care)
• Financial assistance
National MS Society
Resources for Clinicians
•
MS Clinical Care Network
(www.nationalMSsociety.org/MSClinicalCare;
healthprof_info@nmss.org)
– Clinical consultations with MS specialist physicians
– Literature search services
– Professional publications (Clinical Bulletins; Expert Opinion
Papers; Talking with Your MS Patients about Difficult Topics;
Pamela Cavallo Education Series for nurses, rehab professionals,
mental health professionals, and pharmacists
– Quarterly e-newsletter for healthcare professionals
– Professional Education Programs (Nursing, Rehab,
Mental Health)
– Consultation on insurance and long-term care issues