Multiple Sclerosis:
An Overview for
Pharmacists
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
1396: Earliest Recorded Case of MS
From Sister Lidwina to the present…
• 1868—Jean-Martin Charcot describes the disease and
finds MS plaques (scars) on autopsy.
• 1878—Louis Ranvier describes the myelin sheath (the
primary target of MS in the central nervous system).
“Multiple sclerosis is often one of the most difficult
problems in clinical medicine.” (Charcot, 1894)
“When more is known of the causes and…pathology of the
disease… more rational methods may brighten the
therapeutic prospect.” (Gowers, 1898)
• 1981—1st MRI image of MS is published.
From Sister Lidwina to the present, cont’d
• 1993—The first disease-modifying agent for MS—
Betaseron—is approved in the U.S.
• 1998—Bruce Trapp confirms that the nerve fibers
themselves are irreversibly damaged early in the
disease course (probably accounting for the permanent
disability that can occur).
• 2009—Today, there are seven medications approved in
the U.S. for the treatment of MS and more in the pipeline.
Today there are 400,000 people with MS in the U.S.
and 2.5 million worldwide.
What MS Is:
• MS is thought to be a disease of the immune system—
perhaps autoimmune.
• The immune system attacks 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
What happens
to the myelin and nerve fibers?
What are possible symptoms?
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MS symptoms vary between individuals and are unpredictable
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Fatigue (most common)
Decreased visual acuity,
diplopia
Bladder and/or bowel
dysfunction
Sexual dysfunction
Paresthesias (tingling,
(numbness, burning)
Emotional disturbances
(depression, mood swings)
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Cognitive difficulties
(memory, attention,
processing)
Pain (neurogenic)
Heat sensitivity
Spasticity
Gait, balance, and
coordination problems
Speech/swallowing
problems
Tremor
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
What is a clinically-isolated syndrome
(CIS)?
• First neurologic episode caused by demyelination in the
CNS
• May be monofocal or multifocal
• May or may not go on to become MS
 CIS accompanied by MS-like lesions on MRI is more
likely to become MS than CIS without lesions on MRI
• Interferon medications delay second episode
 Avonex, Betaseron, Extavia, Copaxone approved
for this use
 Rebif has demonstrated its effectiveness
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 (further from the
equator)
What is the genetic factor?
• 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 (aka multiplex families)
What is the prognosis?
• One hallmark of MS is its unpredictability.
 Approximately 1/3 will have a very mild course
 Approximately 1/3 will have a moderate course
 Approximately 1/3 will become more disabled
• Certain characteristics predict a better outcome:
 Female
 Onset before age 35
 Sensory symptoms
 Monofocal rather than multifocal episodes
 Complete recovery following a relapse
What are the
different patterns (courses) of MS?
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Relapsing-Remitting MS (RRMS)
Secondary Progressive MS (SPMS)
Primary Progressive MS (PPMS)
Progressive-Relapsing MS (PRMS)
Increasing disability
Relapsing-Remitting MS
time
Increasing disability
Secondary-Progressive MS
time
Increasing disability
Primary-Progressive MS
time
Increasing disability
Progressive-Relapsing MS
time
An Overview of Treatment Strategies
Who is on the MS “Treatment Team”?
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Neurologist
Urologist
Nurse
Physiatrist
Physical therapist
Occupational therapist
Speech/language
pathologist
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Psychiatrist
Psychotherapist
Neuropsychologist
Social worker/Care
manager
• Pharmacist
What are the treatment strategies?
• Gone are the “Diagnose and Adios” days of MS care
• Management of MS falls into five general categories:
 Treatment of relapses (aka exacerbations, flare-ups,
attacks—that last at least 24 hours)
 Symptom management
 Disease modification
 Rehabilitation (maintain/improve function)
 Psychosocial support
How are relapses treated?
• Not all relapses require treatment
 Mild, sensory sx are allowed to resolve on their own.
 Sx that interfere with function (e.g., visual or walking
problems) are usually treated
• 3-5 day course of IV methylprednisolone—with/without an oral
taper of prednisone
 High-dose oral steroids used by some neurologists
• Rehabilitation to restore/maintain function
• Psychosocial support
How is the disease course treated?
• Ten disease-modifying therapies are FDA-approved for relapsing
forms of MS:
 interferon beta-1a (Avonex® and Rebif®) [inj.]
 interferon beta-1b (Betaseron® and Extavia®) [inj.]
 glatiramer acetate (Copaxone®) [inj.]
 fingolimod (Gilenya™) [oral]
 teriflunomide (Aubagio®) [oral]
 Dimethyl fumarate (Tecfidera™
 natalizumab (Tysabri®) [inf]
 mitoxantrone (Novantrone®) [inf]
What do the disease-modifying
drugs do?
• All reduce attack frequency and severity, reduce scarring
on MRI, and probably slow disease progression.
• These medications do not:
 Cure the disease
 Make people feel better
 Alleviate symptoms
How important is early treatment?
• The Society’s National Medical Advisory Committee
recommends that treatment be considered as soon as a dx
of relapsing MS has been confirmed.
 Irreversible damage to axons occurs even in the earliest
stages of the illness.
 Tx is most effective during early, inflammatory phase
 Tx is least effective during later, neurodegenerative
phase
• No treatment has been approved for primary-progressive
MS.
Approximately 60% of PwMS are on Tx
What factors affect treatment adherence?
• Patient readiness is key
• Factors affecting readiness include:
 Lack of knowledge about MS
 Denial of illness
 Unrealistic expectations of treatment outcomes
 Side effects
 Cultural factors
 Lack of support (medical team, family)
 Distrust of medical community and/or prescription
medications
Treatment Challenges in MS Research
• Current therapies—primarily anti-inflammatory
• Future therapies
 Design selective therapies that target very specific
components of the immune system
 Utilize combination of strategies:
 Anti-inflammatory
 Neural repair
 Neuroprotection
New Treatments on Horizon
• Enhancement of Existing Therapies
• Potential Therapies
 Oral
• estrogens/testosterone
• laquinimod
 Parenteral
• rituximab (Rituxan)
• alemtuzumab (Lemtrada)
• declizumab (Zenapax)
• dirucotide
Managing MS Symptoms
• Symptom management begins on Day 1 and continues
throughout the disease course.
• Symptom management is an art.
• Virtually every medication used to treat MS symptoms is
used off-label.
• Effective symptom management involves medication,
rehabilitation strategies, emotional support—and good
coordination of care.
Managing MS Fatigue
• > 80% of people with MS experience fatigue; many identify it
as their most disabling
• Along with cognitive dysfunction, fatigue is the most
common cause of early departure from the workforce
• MS fatigue is easily misunderstood by family members and
employers as laziness or disinterest
• MS fatigue is multi-faceted
Managing MS Fatigue, cont’d
• Identify/address contributory factors
 Disrupted sleep; muscle fatigue; disability-related
fatigue; depression; medications
• Develop comprehensive treatment plan
 Medications: amantadine; modafinil
 Energy management: planning/prioritizing; mobility aids
 Exercise regimen
Managing Bladder Dysfunction
• > 75% of people with MS will experience bladder problems.
• Bladder dysfunction is a major cause of morbidity,
embarrassment, and social isolation.
Managing Bladder Dysfunction
• Storage dysfunction
 Small, spastic bladder in which small quantity of urine
triggers the urge to void
 Sx include: urgency, frequency, incontinence, nocturia
 Tx includes: anticiholinergic/antimuscarinic medication
• Emptying dysfunction
 Bladder fails to empty  risk of UTI
 Sx include: urgency, frequency, nocturia, incontinence Tx
includes: ISC and anticholinergic/antimuscarinic medications
Managing Bowel Problems
• Experienced by 50% of people with MS
 Constipation—most common
• “Diarrhea” (related to impaction)
 Bowel incontinence—least common
• Managed best with regular bowel routine
 Adequate fluid/fiber intake
 Exercise
 OTC products as needed
 Anticholinergic medications added to
manage incontinence
Managing Spasticity (increased muscle
tone)
• Experienced by 40-60% of people with MS
(more common in the lower extremities)
• Management strategies:
 Stretching
 Oral medication (baclofen, tizanidine, clonazapam,
gabapentin, cyproheptidine, dantrolene, dopaminergic
agonists
 Baclofen pump
 Botox injections; nerve blocks; surgery
• Some spasticity is useful to counteract weakness
Managing Primary Sexual Dysfunction
• 40-80% of men and women with MS
 Reduced libido (behavioral/environmental strategies)
 Sensory disturbances (anticonvulsant medications)
 Anorgasmia (body-mapping exercises)
• Women
 Reduced lubrication (gels)
• Men
 Erectile dysfunction (pharmacotherapy;
implants)
Managing Secondary/Tertiary Sexual
Dysfunction
• Secondary dysfunction (other contributory factors)
 Managing MS symptoms that interfere with sexual
activity/pleasure (fatigue, spasticity, etc.)
 Managing medications to promote sexual comfort and
responsiveness (anticholinergics; antidepressants, fatigue
and spasticity meds)
• Tertiary dysfunction (feeling; attitudes)
• Education; counseling
Managing Cognitive Dysfunction
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Occurs in 50-60% of people with MS
Ranges from relatively mild to quite severe
Correlates with number of lesions and lesion area on MRI, as well
as brain atrophy
Can occur at any time but is more common later in the disease
Can occur with any disease course, but is slightly more likely in
progressive MS.
Being in an exacerbation is a risk factor for cognitive dysfunction.
Most common problems: memory; attention/concentration;
information processing
Treatments:
 Disease-modifying therapy to prevent relapses
 Cognitive rehabilitation: primarily compensatory
Managing Depression
• >50% of people with MS will experience a
major depressive episode.
• Suicide in MS is 7x higher than in the general population.
 Greatest risk factor for suicide in MS is depression.
• Depression is under-recognized, under- diagnosed and
under-treated in MS
• Recommended tx = psychotherapy + medication + exercise
Managing Pain
• 75% of people with MS experience pain
• Neuropathic (central) pain
 Paroxysmal pain (trigeminal neuralgia; headache)
• Anticonvulsants
 Continuous pain (dysesthesias)
• Tricicyclics; anticonvulsants
• Nociceptive (secondary) pain
 Musculskeletal pain
 Physical therapy; NSAIDs
 Spasticity—As described previously
Managing Ataxia/Tremor
• Incidence is unknown
• Potentially severely disabling
• No effective treatments at this time
 Medications that may be tried:
• propranolol; primidone; acetazolamide; buspirone;
clonazepam
 Occupational therapy
• Weighting; assistive devices
 Thalamic surgery for tremor (generally poor results)
Serious Complications
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Urosepsis
Aspiration pneumonia
Pulmonary dysfunction
Skin breakdown
Untreated depression
Osteoporosis
What can people do to feel their best?
• Balance activity with rest.
• Talk with their doctor about the right type/amount of
exercise for them.
• Eat a balanced low-fat, high-fiber diet.
• Avoid heat if they are heat-sensitive.
• Drink plenty of fluids to maintain bladder health and
avoid constipation.
• Follow the standard preventive health measures
recommended for their age group
What else can people do to feel their best?
• Reach out to their support system; no one needs to be
alone in coping with MS.
• Stay connected with others; avoid isolation.
• Become an educated consumer.
• Make thoughtful decisions regarding:
 Disclosure
 Choice of physician
 Employment choices
 Financial planning
• Be aware of common emotional reactions.
The Allure of CAM
Understanding CAM’s Allure
• MS treatments are only partially effective.
• Personal testamonials are extremely powerful.
• Many people believe “Safe…natural…healthy…effective…”
and distrust the effects of mainstream medicine.
• It feels good to “take charge” of a chronic, unpredictable disease.
The Use of Complementary and
Alternative Medicine (CAM) in MS
• Used by 50-88% of people with MS, generally in
conjunction with conventional treatments
• Practitioners optimize the placebo effect
• Recommendations to patients from Allen Bowling,
MD, PhD
 Consider conventional medicine first
 Learn about effectiveness, safety, cost
 Discuss it with your physician
 Use caution (“buyer beware”)
 Remember: MS involves excessive immune
activity; no need to “boost” immune system”
Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).
New York: Demos Medical Publishing, 2007
Possibly Beneficial CAM Interventions
• Diet low in saturated fat and enriched in polyunsaturated
fatty acids (may suppress immune system)
• Acupuncture: anxiety, bladder; depression; pain; sleep
• Massage: anxiety, pain, depression; pain; spasticity
• Meditation: anxiety, pain, depression, pain
• Exercise (T’ai chi; yoga): fatigue; anxiety, depression;
weakness; walking
• Cooling: fatigue; spasticity; walking
• Biofeedback: anxiety; pain; sleep; bladder
Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).
New York: Demos Medical Publishing, 2007
Dietary Supplements to be Avoided
Supplements that may stimulate the immune system:
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Alfalfa
Ashwagandha
Astragalus
Cat’s claw
Garlic
Licorice
Melatonin
• Oligomeric
proanthocyanidins
• Pycnogenol
• Saw palmetto
• Selenium
• Stinging nettle
• Vitamin A
• Zinc
Bowling AC. Complementary and Alternative Medicine in Multiple Sclerosis (2nd ed.).
New York: Demos Medical Publishing, 2007
So what do we know about MS?
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MS is a chronic, unpredictable disease
The cause is still unknown
MS affects each person differently; symptoms vary widely
MS is not fatal, contagious, directly inherited, or always
disabling
• Early diagnosis and treatment are important
 Significant, irreversible damage can occur early on
 Available treatments reduce the number of relapses and may
slow progression
• Treatment includes: attack management, symptom management,
disease modification, rehab, emotional support
NMSS Resources for Patients and Families
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40+ chapters around the country
Web site (www.nationalmssociety.org)
Access to information, referrals, 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
Society Resources for Professionals
• MS Clinical Care Network
Website: www.nationalMSsociety.org/MSClinicalCare
Email: healthprof_info@nmss.org
 Comprehensive MS library/literature search
services
 Clinical consultations with MS specialists
 Professional publications
 Professional education programs (medical,
rehab, nursing, mental health)
 Consultation on insurance and long-term care
issues