Multiple Sclerosis

Multiple Sclerosis (Diagnosis and Management of Current Therapies) Patient Safety
William Sonnenberg, MD, Titusville
Disclosures:
Speaker discloses that he is on the Speaker’s Bureau for Forest Labs.
The speaker has attested that his presentation will be free of all commercial bias toward a
specific company and its products.
The speaker indicated that the content of the presentation will not include discussion of
unapproved or investigational uses of products or devices.
3/17/2014
Multiple Sclerosis
William R. Sonnenberg, MD, FAAFP
DISCLOSURE
• The speaker is on the speaker Bureau for Forrest Pharmaceuticals.
Risk factors for multiple sclerosis include all of the following except:
1.Childhood high altitude
2.Female
3.Smoking
4.Alcohol
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Most common type of multiple sclerosis is
1.Relapsing‐remitting
2.Primary progressive
3.Secondary progressive
4.Progressive relapsing
Pathognomonic feature of multiple sclerosis are:
1.Optic neuritis
2.Dawson’s fingers
3.Tingling
4.Sexual dysfunction
Annette Funicello
• Showed poor balance during, Back to the Beach
• Went public in 1991
• Final years in wheelchair
• Could not read nor write
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Definition of Multiple Sclerosis
• Inflammatory demyelinating disease of CNS with:
• Dissemination in space
• Dissemination in time ( 3 months)
• No alternative neurologic disease
• MS is a clinical diagnosis
Epidemiology • 20‐45 years of age
• Women twice as likely
• Northern Europeans (>90% white)
• Scandinavian ancestry
• High socioeconomic status
• Northern latitude
Epidemiology
• Incidence is increasing in white women
• 400,000 Americans
• 2.5 million worldwide 3
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Those at Less Risk
• Gypsies
• Inuit's
• Native Americans
• Japanese
MS and Latitude
Infection and MS
• EBV seems prerequisite
• Clinical mono increases risk 13‐fold
• Less childhood infections increases risk
• 1/3 of relapses preceded by infectious trigger
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Genetics and MS
• Risk is 1/500 for Caucasians • First degree relative 2% ‐4%
• <40% concordance rate for identical twins
Vitamin D and MS
• 50 nmol/L increment in 25(OH)D
• 57% lower rate new lesions
• 57% lower relapse
• 25% lower increase in T2 lesion volume
• 0.41% lower brain volume loss
JAMA Neurol. Published online January 20, 2014
Smoking and MS
• Current and past smokers
• Risk of progressing from relapsing intermittent to secondary progressive was 3.6 times higher
• 30% more likely to get MS
Hernan, M. Brain, March 9, 2005. Miguel A. Hernan, MD, DrPH, department of epidemiology, Harvard School of Public Health, Boston. Nicholas LaRocca, PhD, director of health care delivery and policy research, National MS Society
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Alcohol and MS
• Epidemiological Investigation of Multiple Sclerosis (EIMS)
• Heavy drinkers
• OR 0.6 women
• OR 0.5 men
• Seemed to attenuate effects of smoking
Anna Karin Hedström, MD et al. Alcohol as a Modifiable Lifestyle Factor Affecting Multiple Sclerosis Risk. JAMA Neurology, January 2014
Oral Contraceptives
• 305 women, ages 18‐48 with MS compared to 3050 matched controls
• 30% increased risk with at least 3 months use
Kaiser Permanente, Feb 2014 MS Subtypes
• Asymptomatic
• Symptomatic
• Relapsing‐remitting (85% at onset)
• Primary progressive (10%)
• Secondary Progressive (transitional form)
• Progressive Relapsing (5%)
Lublin F, et al Neurology 1996
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MS Subtypes
Primary Progressive
• 10% ‐15%
• Men = women
• Older age • Late 30’s‐early 40’s
• Slowly worsening spinal cord syndrome effecting walking
White Matter Disease
White Matter
Gray Matter
• Vision
• Dementia
• Motor skills
• Seizure
• Sensory skills
• Movement disorder
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Demyelination
• Conduction block at lesion site
• Slow conduction on affected nerve
• Fatigue due to compensation of slow conduction
• Myelin can regenerate, resulting in remission
Symptoms Suggestive of MS
• Blurred or double vision
• Lhermitte’s sign
• Fatigue
• Heat sensitivity
• Bladder symptoms
• Depression • Numbness, tingling, pain
Lhermitte’s Sign
• Barber chair sign
• Electrical sensation running down back and limbs with neck flexion
• Not unique to MS
• Transverse myelitis, trauma, radiation
• SSRI discontinuation
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Signs of MS
• Action tremor
• ↓ perception of pain, vibration, position
• ↓ strength
• Hyperreflexia, spasticity, Babinski’s sign
• Impaired coordination and balance
Visual Symptoms
• Blurred or double vision
• Impaired acuity
• Impaired red color perception
• Optic disc pallor
• Afferent pupil defect
• Disconjugate eye movements
• Nystagmus
Emotional Manifestations
•Anger
•Depression
•Euphoria
•Decreased executive functions
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Neurologic Exam
• Attention, psychomotor slowing
• Cranial nerves
• Visual acuity, fundus, fields, EOM
• Reflexes
• Babinski, asymmetry
• Sensory
• Gait 25” timed walk
• Bladder ‐ PVR
Right Internuclear Ophthalmoplegia
• Medial longitudinal fasciculus
Optic Neuritis 10
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Optic Neuritis
• 15‐20% presenting feature
• Occurs 50% at some time during disease course
• 31% recur in 10 years
• 10 year follow‐up, 38% get MS after optic neuritis Laura J. Balcer, M.D., M.S.C.E.
N Engl J Med 2006; 354:1273‐1280
Symptoms
• Monocular vision loss, central
• Color desaturation, especially red
• Improves within 2 weeks
• Subtle symptoms persist
• Never seems right
• Washed out, blurred
Findings
•Afferent pupillary defect
•Impaired visual acuity
•Impaired color vision
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Afferent Pupillary Defect
Optic disc in MS
Balcer LJ. N Engl J Med 2006;354:1273‐1280.
Optic Neuritis MRI
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MS Studies
MRI in Multiple Sclerosis
• Most useful confirmatory test, 98% sensitive
• High signal in white matter or spinal cord on T2 weighted images
• Abnormal in almost all MS patients with symptoms 13
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MRI Brain Lesions for MS
• High signal on T2‐weighted and FLAIR MRI sequences (>9 lesions)
• When actively inflamed, often enhanced with gadolinium contrast
• Abuts ventricles (often perpendicular)
• Juxtacortical position (gray‐white junction)
• Involvement of brainstem, cerebellum, or corpus callosum
T1‐Weighted Images
• Black holes – permanent axonal damage
FLAIR MRI
• Fluid attenuation inversion recovery
• Digitally subtract out water
• Most sensitive for MS
• Not specific for demyelination
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Dawson’s Fingers –
Pathognomonic
T2‐Weighted Images
Spinal MRI Images
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MRI Progression
Sensory Evoked Potential
•Visual most useful
•Subclinical lesions in sensory pathways
Visual Evoked Potentials
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CSF Analysis
•Increased IgG concentration
•Oligoclonal bands not matching serum bands
Oligoclonal Bands in CSF
Red Flags for Misdiagnosis of MS
• MRI changes without clinical correlate
• Known psychiatric disease
• Normal neurologic examination
• Atypical clinical features
• Disease onset at the extremes of age
• Extraneural systemic disease
• Prominent gray matter symptoms
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Serologic Testing
•B12, TSH, ESR
• B12 tends to mimic disease and is low in disease
•ANA
•Lyme titer
•Syphilis, HIV
Management of Multiple Sclerosis
Treatment Goals
•No cure
•Treat relapses
•Prevent relapses
•Treat chronic progression
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Acute Exacerbations • IV or PO methylprednisolone for 5 days, no taper
• Anti‐inflammatory, restores blood‐brain barrier, reduces edema
• Shorten duration, accelerate recover
• Long term benefit unsure
Options for Acute Attacks
•Plasmaphoreisis
•Immunoglobulin Disease‐Modifying Meds
First Line
Second Line
• Interferon‐1a
• Natalizumab
• Interferon–1b
• Mitoxantrone
• Glatiramer
• Teriflunomide
• Fingolimod
• Dimethyl fumarate
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Immunomodulation
•Start ASAP after diagnosis of MS with relapsing course
•Consider after first attack with high risk
β Interferons • 1/3 reduction of relapses
• 50‐80% reduction in inflammatory lesions on MRI
• May improve quality of life and cognitive function
• Avonex, Betaseron, Rebif β Interferons – Side Effects
• Lump at injection site or necrosis
• Flu‐like illness – 60%
• Depression, suicidal ideation
• Neutralizing antibodies – 40%
• Effect is variable
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Glatiramer (Copaxone)
• Mimic and compete with myelin basic protein
• SQ once daily
• ↓ relapses by 1/3
• ↓ inflammation on MRI by 1/3
Glatiramer
• Panic attacks
• Chest tightness,
• Palpitations, • Anxiety, • Dyspnea
• Nausea
Fingolimod (Gilenya)
• Fungal derived, sequester lymphocytes in lymph nodes
• First PO med
• ↓ relapses by ½
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Fingolimod (Gilenya)
• Bradycardia
• EKG monitor before and 6 hours after first dose
• Vitals hourly
• Macular edema
• Basal skin cancer
Natalizumab – Second Line
• Monoclonal antibody
• Monthly IV infusion
• Progressive multifocal leukoencephalopathy
• Over 130 cases in MS patients
Mitoxantrone – Second Line
• Antineoplastic
• Irreversible cardiomyopathy in 25%
• 10% decrease in ejection fraction
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Vitamin D
• Recommended
• Doses not determined
• 2000 – 20,000 IU/day
• 10 nmol/L increases reduces relapse by 12%
• 50 nmol/L reduces relapse frequency by 50%
Symptom Control
Adaptive Equipment
• Cups with lids
• Scoop dishes
• Utensils for eating
• Elastic shoe laces
• Reachers
• Communication keyboards
• Braces, walkers, wheelchairs, splints
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Spasticity
• Water therapy, yoga, PT
• TENS unit
• Botox
• Meds
• Baclofen
• Tiranidine
• gabapentin
Bladder Dysfunction
• Rule out infection
• Oxybutrin or tolterodine for failure to store urine
• Alpha blockers for urinary retention
Sexual Symptoms
•↓ arousal, sensation, orgasms
•PDE 5 inhibitors
•Lubricants
•Foreplay
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Depression
•SSRI’s
•Amitriptyline
• Headache
• Pain syndromes
Fatigue
• Energy conservation
• Vitamin D • Sleep hygiene
• Amantadine
• Modafinil
• SSRI’s
Pain
•Acupuncture
•Manipulation
•Tricyclics
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Prognosis
• Most early cases remitting relapsing
• Most get secondary progressive in 6‐10 years
• Unaffected by Rx
• Lifespan not affected
• 33% can live independently
• 33% have severe disability
• Disease course > 30 years
Favorable Prognosis
• Female
• Low relapses/year
• Complete recovery after first attack
• Long interval between first and second attack
• Low disability at 2‐5 years
Favorable Prognosis
•Sensory symptoms
•Younger age at onset
•Later cerebellar involvement
•Involvement of only one CNS system at onset
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Summary
• Clinical diagnosis
• MRI supports diagnosis
• LPs for other diseases
• No cure
• Treatment is symptomatic and for tertiary prevention
• Corticosteroids for acute exacerbations
• Team approach
Risk factors for multiple sclerosis include all of the following except:
1.Childhood high altitude
2.Female
3.Smoking
4.Alcohol
Most common type of multiple sclerosis is
1.Relapsing‐remitting
2.Primary progressive
3.Secondary progressive
4.Progressive relapsing
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3/17/2014
Pathognomonic feature of multiple sclerosis are:
1.Optic neuritis
2.Dawson’s fingers
3.Tingling
4.Sexual dysfunction
Patient Support
• National MS Society
• www.nmss.org
• Consortium of MS Centers
• www.mscare.org
• Multiple Sclerosis Association of America
• www.msaa.com
• Paralyzed Veterans of America
• www.pva.org
• VA MS Centers of Excellence (East & West)
• www.va.gov/ms
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