Why pediatric MS important

  • Treating kids is always important

  • Many missed opportunities because diagnosis is delayed, yet early treatment is critical

  • Studying pediatric MS may increase our understanding of the pathogenesis of the disease and help all patients with MS

Unique Challenges

          The diagnosis of pediatric MS is increasingly being considered

 - Wide spread availability of MRI

 - Need for early diagnosis & treatment

          Demyelination in the presence of ongoing myelination within the brain raises unique issues

          Rapid diagnosis and treatment is limited by lack of clinical experience


          2.5 million people affected world-wide

          3.5-5%  symptoms before 18 years

        (100,000-200,000 world-wide)

          0.2-0.7% onset before 10 years of age

          MS as young as 2 years is reported but uncommon

Gender Distribution


Female: Male


< 10 years

0.6: 1

Simone 2002

10 – 14 years


Simone 2002

13 years


Boiko 2002

14 years


Boiko 2002


          Acute Disseminated Encephalomyelitis  (ADEM)

          Clinical Isolated Syndrome (CIS)

          Neuromyelitis Optica (Devic Syndrome)

          Pediatric Multiple Sclerosis  (Pediatric MS)


          Acute Demyelinating CNS Disorder

          Usually a one time event

          Typically Affects Children

          Monophasic Course

          Focal or Multi-focal Neurologic S&S 

           Multi-focal Demyelinating Lesions (MRI),  grey and white matter

          Behavioral/ or Mental Status Changes


          Prodromal Illness (≥70 %)

          Fever, Headache, Nausea/Vomiting/ ¯ Appetite, Lethargy


ADEM   Clinical Characteristics

Signs & Symptoms evolve over time

                                  Maximal deficits reached ~ 1-2 weeks


                                                 rapid / or weeks to months

                                                 may / may not be complete

                                   Repeat MRI ® resolution / no new lesions

ADEM:  Laboratory Findings

CSF                         mild pleocytosis(↑wbc)

                                                + ↑ protein       

                                                + OCB (Oligoclonal Bands) / IgG production

(uncommon -    transient)

MRI                        white matter and grey matter lesions

                                                  (bilateral, asymmetric)

                                                Usually spare periventricular areas

                                                + Basal ganglia involved

                                                lesions highly variable size and number

                                                punctate - large & confluent - tumor-like

                                                Usually resolve


                    At onset MRI   8 week f/u

At onset                                                                     8 wk f/u



ADEM Differential Diagnosis

  • Encephalitis / Infection

  • Vasculitis

  • Leukodystrophy

  • Mitochondrial Cytopathies

  • Sarcoidosis

  • Histiocytic lymphangiomatosis

  • Tumors / glioblastoma

  • Multiple Sclerosis



  • Measles -20-30% deaths

  • Influenza A or B

  • Hepatitis A or B,

  • Coxsackie virus

  • Vaccinia

  • winter/spring respiratory viruses

  • Herpes virus infections 

  • (HSV,VZV, HHV6, CMV,  EBV)                                    




                                Diptheria -Tetnus-Pertussis

                                Hepatitis B


                                                Vaccines now devoid of neural elements

                                                Successful immunization programs, virtual eradication of                                                                                              small pox disease

ADEM Evaluation




        IgG Index; OCB

        R/O CNS infection

CSF profile, CSF viral & bacterial cultures

 PCR- especially for Herpes Simplex Virus

 Lyme titer

Measles Ab


CBC/diff, Electrolytes, LFTs, ESR

T4/TSH, B12, Biotinase

ANA, Anticardiolipin Ab, Antiphospholipid Ab, ACE

Lupus Anticoagulant


CADASIL, LHON mutation

Mitochondrial gene mutation



ADEM treatment

  • Corticosteroids

    • Anti-inflammatory and Immunosupressive

    • Anecdotal Reports

  • Supportive Care

  • Symptomatic Treatment

  • Therapy targeted to immune-mediated process

  • Currently, no treatment trials or proven protocols for ADEM


ADEM- the dilemma

  • ADEM considered an acute monophasic illness

  • Most clinicians acknowledge ADEM may recur

                           myriad of terms found in the literature





                                        steroid dependent

  • Clinicians also acknowledge –

    • some children with ADEM  may go on to develop MS


Neuromyelitis Optica  (Devic’s)

  • Absolute criteria

    • Hx of ON or recurrent ON

    • Hx spinal cord symptoms

    • Spinal cord lesion(s) extending 3 or more segments

    • Normal brain MRI

    • CSF shows pleocytosis (>50 leukocytes)

    • May show NMO antibodies


Disease Courses in MS: Types of MS

Disease Courses in MS


Unusual Demographic Pattern

  • Different distribution of ethnic groups among

    • adults with MS

    • children referred for MS who had other diagnoses

    • and children with MS

    • More severe in non Caucasians??

Adults with MS Seen at the MS Center at Stony Brook

MS Patients Demographics


Frequency of Pediatric MS

  • Data from 149 MS pediatric MS cases from 4 Italian Neurological clinics with 3375 MS patients (Ped MS compared to 923 Adult MS) :                

    • onset before age 16 (4.4%-7.9%)

    • onset before 13 yrs in 1.2%

    • onset before 11 yrs in 0.5%

    • Ghezzi, Multiple sclerosis, 1997


Why are kids different?

  • Exposures

  • Immune system “primed”

  • Growing pediatric brain…repairs

  • Differential in pediatrics


Differences between Adults and Children with MS

  • Less common

  • More often RR onset

  • Overlap in clinical presentation

  • Response to disease modifying therapy

    • So far seems similar (?)

  • Conversion to SP somewhat slower (?)

  • Very severe subset (?)

  • Demographic pattern may differ?


Differences between Adults and Children with MS

  • Average time to recovery shorter

    • Kids recover 2-4 weeks faster than adults

  • Lower overall disability after attack

  • Higher relapse rate

  • Shorter time between first and second attack

  • Kids may be more likely to have seizures


Pediatric MS Differential Diagnosis

  • Structural lesions

  • Infectious

  • Inflammatory

  • Metabolic/Genetic disorders 

  • Vascular disorders

  • Other


Supporting laboratory findings-CSF for MS

  • Oligoclonal bands

  • IgG index

  • Cell count < 50

  • Protein usually normal or mildly elevated

  • Glucose normal

  • All other studies negative


Clinical Features

  • Relapsing remitting onset usual course

    • ( > 90%)

  • Systemic sx occasionally

  • Onset may be with sensory, gait, visual or balance problems

  • Cognitive problems may be present (33%)

  • OCB usually positive

  • In some regions of the USA: high number of minorities affected


How do these kids present?

  • Optic Neuritis

  • Sensory changes

  • Motor disturbance

  • Ataxia/balance


Presentations in Ped MS

MS Data

Banwell, Neurology in press


Criteria for Pediatric MS

  • Children  < 18 years old, includes < 10 years

  • Dissemination in space and time (hx and exam)

    • No change in mental status typically

  • Barkhof MRI criteria


“McDonald” MRI criteria: TIME

  • 1st scan < 3 months after clinical event, then repeat 2nd scan 3 months from event

    • Gd+ lesion

  • if above not met, repeat scan 3 more mos.

    • Gd+ lesion or new T2


Clinical Management

  • Treatment must involve entire family

  • Education, reassurance

  • Medication for symptom management

    • Urinary dysfunction

    • Spasticity

    • Depression

  • Disease modifying therapy should be given


Experience with Disease Modifying Therapies

  • All DMT medications are well tolerated

  • Side effects similar to that of adults

  • In (< 10 years) on IFN, monitor LFTs at onset

  • Clinical impression is that DMT helps reduce relapses and MRI progression

  • No data on “best” drug for kids


Experience with DMT

  • Some patients require intensive Rx including chemotherapy

  • Side effects are few

  • Adherence is reasonably high

  • Follow-up studies


Experience with Disease Modifying Therapy

  • Monotherapy (first line)               “ABCR”

    • Beta interferon  1a (IM or SC and low dose or high dose)

      • Avonex, Rebif

    • Beta interferon 1b

      • Betaseron

    • Glatiramer acetate

      • Copaxone

    • Mitoxantrone

  • Combination Therapy

    • DMT with pulse IVIG

    • DMT with pulse steroids

    • Pulse cytoxan

    • One course of high dose cytoxan


Chemotherapy in Pediatric MS

  • Novantrone

  • Cytoxan

  • Imuran

  • Rituxumab (Rituxan)

  • Natalizumab (Tysabri)


Management of Relapses

  • IV Solumedrol: 3 – 5 days (first line) with or without steroid taper

  • Second Line:

    • Oral steroids moderate or very high doses

    • IVIG

    • Plasmapheresis


Symptomatic Management

  • Attention

    • Cognitive rehab, special accommodations

  • Fatigue

    • Amantadine, modafinil, cooling

  • Memory

    • Aides, ? Donepezil

  • Pain:

    • Anticonvulsants, antispasticity agents, anti-inflammatory, physical therapy, exercise

  • Depression

    • Antidepressants

  • Spasticity

    • Antispasticity agents, Baclofen pump

  • Bladder dysfunction

    • Oxybutynin, Self catheterization

  • Nutrition

  • Rest

  • Plan activities

  • Heat

  • School modifications

    • Preferential seating, test modifications, locks, class schedules


Special needs for families with child with MS

  • Ped MS patient is isolated

  • Families are frightened

  • Current support mechanisms are limited

  • Special issues relate to school and social interactions


Psychosocial problems

  • Challenges sense of self (area of vulnerability in teens)

  • Disrupts school

    • Lost days

    • Emotional changes

    • Impaired physical functioning

  • Family stress

  • Cognitive consequences


Causes of Psychosocial Problems

  • Issues specific to MS

    • Rare in children

    • Physical symptoms (vision,motor, bladder)

      • Wax and wane

    • Uncertainty of the disease course

    • Uncertainty of treatment effect

    • Unpleasant treatment modalities

      • Injection phobia

      • Medication side effects



  • On the family

    • Increased stress and anxiety

      • Fear for the future

      • Grieving loss of the healthy child

    • Variable coping skills

    • Financial planning

  • On the school experience

    • Missed school days

    • Lack of awareness by teachers

    • Academic declines

    • Long range, academic and career planning


Role of health care provider

  • Encourage open communication

  • Involve family and child with decision making process

  • Medication choices to fit child’s lifestyle

  • Continuously re-evaluate goals and plans

  • Provide reassurance

    • Be available to child

    • Family

  • Emphasize there are others affected, “you are not alone”

    • Provide resources, ie on-line secure chat rooms

    • Parental telephone support networks


Weekend Retreat

  • Unique camp experience for teens and pre-teens with MS 

    • Kayaking, Ropes Course, Sailing

    • Professional recreational therapists

    • Nurse practitioner on site; On call MS neurologist


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