Multiple Sclerosis: Overview for Dentists

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Multiple SclerosisOverview for Dentists
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What does MS look like?

• Juliaa 35yo white married mother of 3 who is
  exhausted all the time and cant drive because of
  vision problems and numbness in her feet
• Jacksona 25yo African-American man who stopped
  working because he cant control his bladder or
  remember what he read in the morning paper
• Mariaa 10yo Hispanic girl who falls down a lot
  and whose parents just told her she has MS
• Lorettaa 47yo white single woman who moved into
  a nursing home because she can no longer care
  for herself

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What else does MS look like?

• Sama 45yo divorced white man who has looked and
  felt fine since he was diagnosed seven years ago
• Karena 24yo single white woman who is severely
  depressed and worried about losing her job
  because of her diagnosis of MS
• Sandraa 30yo single mother of two who
  experiences severe burning pain in her legs and
  feet
• Richardwho was found on autopsy at age 76 to
  have MS but never knew it
• Jeannettewhose tremors are so severe that she
  cannot feed herself

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What MS Is

• MS is thought to be a disease of the immune
  systempossibly autoimmune.
• The primary targets of the immune attack are the
  myelin coating around the nerves in the central
  nervous system (CNSbrain, 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.

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What MS Is Not

• MS is not
• Contagious
• Directly inherited
• Always severely disabling
• Fatalexcept in fairly rare instances
• Being diagnosed with MS is not a reason to
• Stop working
• Stop doing things that one enjoys
• Not have children

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What Causes MS?
Genetic Predisposition
Environmental Trigger
Immune Attack
Loss of myelin nerve fiber
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What happens in MS?
Activated T cells...
...cross the blood-brain barrier
launch attack on myelin nerve fibers...
to obstruct nerve signals
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A Close Look at a Myelinated Axon
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Nerve Damage and Myelin Loss

1. Normally, axons have a protective myelin coating
   that allows conduction of electrical impulses
2. In MS, the immune system destroys myelin,
   resulting in slowing of conduction and exposure
   of axons
3. Exposed axons may then be severed
4. leading to permanent loss of the axon
5. The result is permanent loss of nerve function

Adapted from Trapp BD, et al. The Neuroscientist.
1999548-57.
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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. 1998338278-285. Peterson JW et al.
Neurol Clin. 200523107-129.
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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

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What tests may be used to help confirm the
diagnosis?

• Magnetic resonance imaging (MRI)
• Visual evoked potentials (VEP)
• Lumbar puncture

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Who gets MS?

• Usually diagnosed between 20 and 50
• Occasionally diagnosed in young children and
  older adults
• More common in women than men (gt2-31)
• 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

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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)

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Disease Types

• Clinically isolated syndrome (CIS)
• Relapsing-remitting MS (RRMS)
• About 85 of people are diagnosed with RRMS
• Primary progressive MS (PPMS)
• About 15 of people experience this course
• Secondary progressive
• Most people diagnosed with RRMS will eventually
  transition to SPMS

Lublin et al, 2014
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Clinically Isolated Syndrome (CIS)

• A first neurologic event suggestive of
  demyelination
• Individuals with CIS are at high risk for
  developing clinically definite MS if the
  neurologic event is accompanied by multiple,
  clinically silent (asymptomatic) lesions on MRI
  typical of MS

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Lublin et al, 2014
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Lublin et al, 2014
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Lublin et al, 2014
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Lublin et al, 2014
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Multiple Sclerosis The Natural History
Adapted with permission from JS Wolinsky, MD.
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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

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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

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FDA-Approved Disease-Modifying Drugs
Drug Origin Dosage Freq Route
Glatiramer acetate Random polypeptides 20 mg/40 mg Every day/3x/wk SC
IFNb-1b Recombinant protein 0.25 mg Every other day SC
IFNb-1a IM Recombinant protein 30 mcg 1x/wk IM
IFNb-1a SC IFNb-1a SC Recombinant protein 22 mcg 44 mcg 125 mg 3x/wk 2x/mo SC
Dimethyl fumarate Oral formulation of dimethyl fumarate rapidly hydrolyzed to monomethyl fumarate 24o mg Twice daily Oral
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
Alemtuzumab CD52-directed cytolytic Mab 12 mg/day 5 consecutive days 3 consecutive days 12 mos. later IV infusion
Mitoxantrone Chemotherapy 12 mg/m2 (cumulative lifetime dose lt 140 mg/m2) Every 3 months IV infusion
Natalizumab Humanized Mab 300 mg Every 4 wks IV infusion
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Managing Progressive MS

• Azathiorpine (Imuran)
• Methotrexate
• Mitoxantrone (Novantrone)
• Monthly administration of methylprednisolone
• IVIgG
• Cladribine
• Cytoxan
• Bone marrow transplantation

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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

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MS Symptom Management

• MS symptoms are variable and unpredictable

• Cognitive difficulties (memory, attention,
  processing)
• Heat sensitivity
• Spasticity
• Gait, balance, and coordination problems
• Speech/swallowing problems
• Tremor

• Fatigue (most common)
• Decreased visual acuity, diplopia
• Bladder and/or bowel
  
  dysfunction
• Pain
• Sexual dysfunction
• Paresthesias (tingling, (numbness, burning)
• Emotional disturbances
  
  (depression, mood swings)

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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
108318-327.
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Depression in MSDiagnosis 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)

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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.
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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.
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Cognitive Symptoms
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Cognitive Functions Unaffected in MS

• General intellect
• Long-term (remote) memory
• Recognition memory
• Conversational skill
• Reading comprehension

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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.

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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.
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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.

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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)

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Commonly-Used Medications that Cause Xerostomia

• Antidepressants
• amitriptyline
• duloxetine
• fluoxetine
• paroxetine
• sertraline
• Venlafaxine
• Anti-fatigue Medication
• Amantadine

• Bladder Medications
• darifenicen
• oxybutynin
• propantheline
• solifenacin succinate
• tolterodine
• trospirum chloride
• Antidepressants
• amitriptyline
• duloxetine
• fluoxetine

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Where do we go from here?
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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. 200966(7)821-828
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NMSS Resources for Your Patients

• Nationwide network of 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

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National MS Society
Resources for Clinicians

• Professional Resource Center
  (www.nationalMSsociety.org/PRC
  healthprof_info_at_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