Transcript Progressive MS

Pediatric Neurology
Use of Biologic and
Chemotherapeutic Agents
STATISTICS
400,000 Adults have MS in the US
 8,000-10,000 children have MS in the US
 Another 10,000-15,000 children in the US
experience disorders that may be related
to MS
 Studies suggest 2 to 5% of all people with
MS have a history of symptom onset
before age 18.
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MULTIPLE SCLEROSIS
Multiple sclerosis (or MS) is a chronic, often
disabling disease that attacks the central
nervous system (CNS), which is made up of the
brain, spinal cord, and optic nerves.
 Symptoms may be mild, such as numbness in the
limbs, or severe, such as paralysis or loss of
vision.
 The progress, severity, and specific symptoms of
MS are unpredictable and vary from one person
to another
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PEDIATRIC
MULTIPLE SCLEROSIS
Onset occurs before age 16
 Disease progresses slower than it does in
adults, however permanent disability
occurs at a younger age
 Progressive course at diagnosis and having
more relapses during the first 2 years
increases the rate of disability
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CAUSES OF
MULTIPLE SCLEROSIS
MS is an autoimmune disease
 Genetics
 Gender
* Less than age 10 < males
* Adolescent presentation > females
 Environmental Triggers
* Infectious
* Sunlight Exposure & Vitamin D
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ABNORMALITIES
WHICH OCCUR IN MS
Patches of inflammation begin to occur in areas
of the brain and spinal cord.
 Demyelination – myelin sheaths around the cells
affected by inflammation begin to deteriorate.
 The nerve fibers or axons which are stripped of
protective myelin are destroyed.
 After the myelin sheaths are destroyed, the cells
in the CNS are unable to communicate vital
information to the rest of the body which
results in symptoms of MS.
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DIAGRAM OF
DEMYLINATION
DAMAGED NERVE
FOUR COURSES OF MS

Relapsing-Remitting MS
* Attacks followed by recovery
* 85% of adults initially
* 93-95% of children initially
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Primary-Progressive MS
* Slowly worsening neurologic function from the
* Approximately 10% of adult patients
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Secondary – Progressive MS
* Conversion to progressive phase
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Progressive –Relapsing MS
* Steady worsening of disease from onset
* Less than 5% of adults
SYMPTOMS
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Sensory and Motor Symptoms
Spasticity / Tremors / Ataxia
Visual Problems
Bladder and Sexual Dysfunction
Fatigue
Dysarthria
Pain / L’Hermittee’s Phenomeno
Depression
Paroxysmal symptoms
Seizures
Many of the symptoms they experience are “invisible”, vary in
intensity and come and go randomly.
DIAGNOSTIC WORKUP
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Complete Medical History
Nervous System Functioning: Reflexes/
coordination/ balance/ vision
Diagnostic Tests:
* MRI – locates areas of inflamation, demylination
and size of brain
* Evoked Potential Tests – demylination cause
nerves to conduct impulses slower
* Spinal Tap - presence of protein – oligoclonal
bands – (present in > 90% of children with MS)
MRI FINDINGS
TREATMENT
 Divided into three categories:
1. Treatment of acute attacks
2. Treatments to reduce the number of
attacks and attack severity
3. Treatment of intermittent or
persistent MS symptoms
TREATMENT
ACUTE MS RELAPSES
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Corticosteroids - help to prompt recovery during MS
relapses by reducing inflammation.
Intravenous methylprednisone – 20-30 mg/kg/day (maximum of 1
gram) as single dose for 3 to 5 days
Children with complete resolution receive no further
corticosteroids
Incomplete recovery following IV steroids - oral prednisone
starting at 1mg/kg/day followed by a tapering schedule with
reduction by 5 mg every 2 to 3 days
Intravenous Immunoglobulins – used when sufficient
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clinical recovery does not occur after corticosteroids
IVIg – 2 gms/kg over 2-5 days
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Plasma Exchange – adults for severe relapses not
responsive to steroids – 5 exchanges over 8 to 10 days
TREATMENT
REDUCE NUMBER OF ATTACKS
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Immunomodulatory therapy – decrease
the relapse rate and MRI accrual of new
lesions
Interferon beta – Ib (Betaseron/
Betaferon)
Interferon beta – Ia IM (Avonex)
Interferon beta – Ia (Rebif)
Glatiramer acetate (Copaxone)
TREATMENT
REDUCE NUMBER OF ATTACKS
Immunosuppressive Drugs -- Drugs to
suppress or control the immune system
* Azathioprine
* Cyclophosphamide -significant risks
* Methotrexate – low dose orally - well tolerated
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TREATMENT OPTIONS
CURRENTLY IN ADULTS
WHEN TRADITIONAL TREATMENT FAILS
Natalizumab (Tysabri) – Monoclonal antibody –
prevents inflammatory cells from entering the brain (IV
infusion every 28 days)
 FDA approved for MS in patients over 18 years old who
have failed conventional treatments although long term
safety data unknown
 Cases of Progressive multifocal leukoencephalopathy
(PML), liver dysfunction and skin cancer have been
reported
 All patients on this medication must participate in the
TOUCH program which monitors their current status
and side effect profile (Medical exam/ MRI/ Lab work at
least every 6 months)
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TREATMENT OPTIONS
CURRENTLY IN ADULTS
WHEN TRADITIONAL TREATMENT FAILS
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Mitazantrone (recommended for aggressive
forms of MS which do not respond to first line
therapy – cardiotoxicity limits duration of
therapy)
Methotrexate (experimental – low dose orally
well tolerated)
Cyclophosphamide (experimental – significant
risks)
Cladarabine (experimental– significant risks)
Acyclovir (experimental)
References

Ahorro, J. (2009). Multiple Sclerosis in Children. Multiple Sclerosis Quartely
Report.Volume 28, Number 1.
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Ascherio, A. & Munger, K. (2007). Environmental risk factors for multilpe
sclerosis. Part I: the role of infection. Annals of Neurology, 61 (4), 288-299.

Blckstone, M. (2003). The First Year – Multiple Sclerosis: An Essential Guide
for the Newly Diagnosed. New York: Marlowe & Company.
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Holland, N, Murray, T, & Reingold, S. (2002). Multiple Sclerosis: A Guide for
the Newly Diagnosed. Second Edition. New York: Demos Medical Printing.

Polman, C., Thompson, A., Murray,t. Bowling, A., & Noseworthy, J. (2006).
Mutiple sclerosis: The Guide to Treatment and Management. Sixth Edition.
New York: Demos Medical Publishing.
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Schapiro, R. (2003). Managing the Symptoms of Multiple Sclerosis. Fourth
Edition. New York: Demos Medical Printing.
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National Multiple Sclerosis Society at http://www.nationalmssociety.org