Pediatric NeurologyPediatric NeurologyUse of Biologic and Use of Biologic and Chemotherapeutic Chemotherapeutic AgentsAgents

STATISTICSSTATISTICS400,000 Adults have MS in the US8,000-10,000 children have MS in

the USAnother 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.

MULTIPLE MULTIPLE SCLEROSISSCLEROSIS

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

PEDIATRIC PEDIATRIC MULTIPLE MULTIPLE SCLEROSISSCLEROSIS

Onset occurs before age 16Disease 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

CAUSES OF CAUSES OF MULTIPLE MULTIPLE SCLEROSISSCLEROSISMS is an autoimmune diseaseGeneticsGender * Less than age 10 < males * Adolescent presentation >

femalesEnvironmental Triggers

* Infectious * Sunlight Exposure & Vitamin D

ABNORMALITIESABNORMALITIESWHICH OCCUR IN MSWHICH OCCUR IN MSPatches 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.

DIAGRAM OF DIAGRAM OF DEMYLINATIONDEMYLINATION

DAMAGED NERVEDAMAGED NERVE

FOUR COURSES OF FOUR COURSES OF MSMSRelapsing-Remitting MS

* Attacks followed by recovery * 85% of adults initially * 93-95% of children initiallyPrimary-Progressive MS * Slowly worsening neurologic function from the * Approximately 10% of adult patientsSecondary – Progressive MS * Conversion to progressive phaseProgressive –Relapsing MS * Steady worsening of disease from onset * Less than 5% of adults

SYMPTOMSSYMPTOMS 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 DIAGNOSTIC WORKUPWORKUP

Complete Medical HistoryNervous System Functioning:

Reflexes/ coordination/ balance/ visionDiagnostic 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 FINDINGSMRI FINDINGS

TREATMENTTREATMENTDivided into three categories:

1.Treatment of acute attacks2.Treatments to reduce the number of attacks and attack severity

3.Treatment of intermittent or persistent MS symptoms

TREATMENT TREATMENT ACUTE MS RELAPSESACUTE MS RELAPSESCorticosteroids - 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 clinical recovery does not occur after corticosteroids

• IVIg – 2 gms/kg over 2-5 daysPlasma Exchange – adults for severe relapses not

responsive to steroids – 5 exchanges over 8 to 10 days

TREATMENTTREATMENTREDUCE NUMBER OF REDUCE NUMBER OF ATTACKSATTACKSImmunomodulatory 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)

TREATMENTTREATMENTREDUCE NUMBER OF REDUCE NUMBER OF ATTACKSATTACKS

Immunosuppressive Drugs -- Drugs to suppress or control the immune system

* Azathioprine* Cyclophosphamide -significant risks* Methotrexate – low dose orally - well

tolerated

TREATMENT TREATMENT OPTIONSOPTIONSCURRENTLY IN ADULTSCURRENTLY IN ADULTSWHEN TRADITIONAL TREATMENT FAILSWHEN TRADITIONAL TREATMENT FAILSNatalizumab (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)

TREATMENT TREATMENT OPTIONSOPTIONSCURRENTLY IN ADULTSCURRENTLY IN ADULTSWHEN TRADITIONAL TREATMENT FAILSWHEN TRADITIONAL TREATMENT FAILSMitazantrone (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)

ReferencesReferences Ahorro, J. (2009). Multiple Sclerosis in Children. Multiple Sclerosis

Quartely Report. Volume 28, Number 1. 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.

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.

Schapiro, R. (2003). Managing the Symptoms of Multiple Sclerosis. Fourth Edition. New York: Demos Medical Printing.

National Multiple Sclerosis Society at http://www.nationalmssociety.org