Treatment issues in Pediatric Multiple Sclerosis
Brenda Banwell, MD, FRCPC Director, Pediatric Multiple Sclerosis Clinic The Hospital for Sick Children University of Toronto
Child with MS
Acute symptoms Chronic immunosupression
MS-targeted therapies
Symptomatic treatment
GOALS OF TREATMENT
Minimal disability Social independence Reproduction & Parenting
Vocational achievement
Adult with MS
Management of the Acute Demyelinating Attack
General Approach
Ensure that symptoms are referable to demyelination Evaluate symptom severity Review prior response to acute management Review timing of last exposure to corticosteroids
IV Solumedrol 20-30 mg/kg/dose X 3 days Improvement Minimal or no improvement
Prednisone start at 1 mg/kg/day, taken as a single morning dose
IV Solumedrol 20-30 mg/kg/dose X 2 additional days
Taper by 5 mg every 2-3 days Improvement
No improvement
IVIg 2 mg/kg total dose if < 50 kg or > 50 kg
Relapse of S+S during taper Improved /stabilized
Initiate immunomodulatory treatment if patient meets criteria for MS diagnosis
1 gm/kg/d x2d
0.4gm/kg/d X5d
MS-targeted immunotherapies in children
Medication
Dose
Frequency
Administration
Side Effects
Interferon Beta-1a (Avonex)
30 mcg
weekly
intramuscular
flu-like symptoms, mild tenderness at the injection site
22/44 mcg
Interferon Beta-1a (Rebif) 8 MIU Interferon Beta-1b (Betaseron)
3 X/week
subcutaneous
flu-like symptoms, bruising, sensitivity of the skin at the injection site
every 2 days
subcutaneous
flu-like symptoms, bruising, sensitivity of the skin at the injection site
20 mg
daily
subcutaneous
Glatiramer Acetate (Copaxone)
bruising, sensitivity of the skin at the injection site, rare “flushing” reaction
Side effects
Flu-like symptoms
Injection-site reaction
premedicate with Advil, pm dosing start with low dose rotate sites, warm soln proper technique
Flushing, palpitations (glatiramer acetate)
Transaminase elevation, leucopenia Depression
reassurance
reduce dose Hold or D/C if marked abn
Safety Monitoring
Contraception counseling Contraception reminder
Liver function CBC
Liver function CBC
Liver function CBC
Baseline
4 weeks
monthly
Chronic Immunosuppresion
Cyclophosphamide
Alkylating agent with cytotoxic and immunosuppressive properties controversial efficacy in large studies recent evidence suggests a role for cyclophosphamide in patients with frequent relapses who fail to respond to MS-disease modifying agents Side effects include: alopecia, hemorrhagic cystitis, infertility, opportunistic infections and an increased risk of future malignancy
Mitoxantrone
Potent immunosuppressant typically prescribed at a dose of 12 mg/m2 IV every 3 months for 2 years) cumulative risk of cardiotoxicity with increasing dose no data in pediatric MS
Symptomatic Therapies
Fatigue
Definition: “sufficient fatigue, or a subjective sensation of reduced endurance, to interfere with enjoyable activities or impair concentration at school” typically manifests as withdrawal from social activities, after school naps, reduced ability to participate in sports occurs in approximately 30% of pediatric MS patients
Treatment of Fatigue
Reduce “wasted” exertion
backpacks home textbooks occupational therapy
Modafinil (Provigil)
shown to improve fatigue in adults well tolerated in pediatric MS (morning dosing) subjective improvements noted
well-tolerated little effect on nocturnal sleep
Amantidine
Rehabilitation
Issues to Consider
Cognition and academic progress Career counseling and reconciliation of career goals with a chronic disease Social integration and self-identity Physical rehabilitation and mobility Autonomy
the
role of independence in medically fragile adolescents
Acknowledgements
• • • • • • • • • •
Lynn MacMillan, Clinic Nurse Jennifer Boyd, Clinical Nurse Specialist Julia Kennedy, Research Manager Jennifer Hamilton, Clinic Co-Ordinator Gillian Bone, Physiotherapy Raymond Buncic, Neuroophthalmology Peter Anderson, Neuropsychology Lois Peltz, Psychiatry Arlette Lefebvre, Psychiatry Rose Geist, Psychiatry