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?

GeneticPredisposition

EnvironmentalTrigger

Immune Attack

Loss of myelin & nerve fiber

What happens in MS?

...cross the blood-brain barrier…

…launch attack on myelin & nerve fibers...

“Activated” T cells...

…to obstruct nerve signals

myelinated nerve fibermyelinated nerve fiber

A Close Look at a Myelinated AxonA Close Look at a Myelinated Axon

Nerve Damage and Myelin LossNerve Damage and Myelin Loss

A.A. Normally, axons have a protective myelin coating that allows Normally, axons have a protective myelin coating that allows conduction of electrical impulsesconduction of electrical impulses

B.B. In MS, the immune system destroys myelin, resulting in slowing of In MS, the immune system destroys myelin, resulting in slowing of conduction and exposure of axonsconduction and exposure of axons

C.C. Exposed axons may then be severed…Exposed axons may then be severed…D.D. ……leading to permanent loss of the axonleading to permanent loss of the axonE.E. The result is permanent loss of nerve functionThe result is permanent loss of nerve function

Adapted from Trapp BD, et al. The Neuroscientist. 1999;5:48-57.

A B C D E

Active Inflammatory Demyelination Active Inflammatory Demyelination and Axonal Transectionand Axonal Transection

• It has been shown that It has been shown that active inflammation active inflammation results in both results in both demyelination and demyelination and axonal transectionaxonal 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?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 MSThe 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 MSClinical Patterns of MS

Time

Secondary progressive

Primary progressive

Progressive relapsing

Adapted from Lublin et al. Neurology. 1996;46:907-911.

Relapsing-remitting

Disease Courses in MS:Disease Courses in MS:DemographicsDemographics

(N=3019)(N=3019)

Jacobs et al. Jacobs et al. Mult Scler.Mult Scler. 1999;5:369-376 1999;5:369-376

Relapsing-remitting55%Secondary-progressive

30%

Primary-Primary-progressiveprogressive

10%10%

Progressive-Progressive-relapsingrelapsing

5%5%

Managing Multiple SclerosisManaging 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 SclerosisManagement of Multiple Sclerosis

• Neurologist• Urologist• Nurse• Primary care physician• Physiatrist • Physical therapist• Occupational therapist• Speech/language

pathologist

• Psychiatrist• Psychotherapist• Neuropsychologist• Social worker/Care

manager• Pharmacist

The MS “Treatment Team”:The MS “Treatment Team”:

FDA-Approved Disease-Modifying DrugsFDA-Approved Disease-Modifying DrugsDrug Origin Dosage Freq RouteGlatiramer acetate Random polypeptides 20 mg Every day 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 mcg125 mg

3x/wk

2x/moSC

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 days3 consecutive days 12 mos. later

IV infusion

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 MSManaging Progressive MS

• Azathiorpine (Imuran) Azathiorpine (Imuran) • MethotrexateMethotrexate• Mitoxantrone (Novantrone)Mitoxantrone (Novantrone)• Monthly administration of methylprednisoloneMonthly administration of methylprednisolone• IVIgGIVIgG• CladribineCladribine• CytoxanCytoxan• Bone marrow transplantationBone marrow transplantation

Relapse ManagementRelapse Management

• Relapse = new symptom or sudden worsening of old Relapse = new symptom or sudden worsening of old symptom lasting at least 24 hours, and usually symptom lasting at least 24 hours, and usually accompanied by a findingaccompanied by a finding

• Treatment with corticosteroids recommended if relapse Treatment with corticosteroids recommended if relapse significantly interferes with everyday functioningsignificantly interferes with everyday functioning– 3-5 day course of high-dose intravenous methylprednisolone 3-5 day course of high-dose intravenous methylprednisolone

with or without oral taperwith or without oral taper– High-dose oral steroids may also be usedHigh-dose oral steroids may also be used

• Rehabilitation can help restore function following a Rehabilitation can help restore function following a relapserelapse

MSMS S Symptom Managementymptom Management

- 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)

• MS symptoms are variable and unpredictable

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:Depression in MS:Diagnosis and TreatmentDiagnosis 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 KnowDepression 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 MSCognitive 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 SymptomsCognitive Symptoms

Severity of Cognitive Changes in Multiple Sclerosis

None50%

Mild40%

Moderate to severe

10%

Cognitive Functions Unaffected in MS

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

Common Misconceptions about Common Misconceptions about MS and cognitionMS 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 CharacteristicsCognition 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 Where do we go from here?here?

Current Treatment PrioritiesCurrent 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

NMSS Resources for Your PatientsNMSS 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

National MS Society National MS Society Resources for CliniciansResources for Clinicians

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