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

Epidemiology

•          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

Age	Female: Male	Ref
< 10 years	0.6: 1	Simone 2002
10 – 14 years	2.6:1	Simone 2002
13 years	3.5:1	Boiko 2002
14 years	7.5:1	Boiko 2002

 Definitions

•          Acute Disseminated Encephalomyelitis  (ADEM)

•          Clinical Isolated Syndrome (CIS)

•          Neuromyelitis Optica (Devic Syndrome)

•          Pediatric Multiple Sclerosis  (Pediatric MS)

ADEM

•          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

•          Seizure

•          Prodromal Illness (≥70 %)

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

 

ADEM   Clinical Characteristics

Signs & Symptoms evolve over time

                                  Maximal deficits reached ~ 1-2 weeks

                                  Resolution

                                                 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

ADEM

                      

At onset                                                                     8 wk f/u

FLAIR MRI

 

ADEM Differential Diagnosis

• Encephalitis / Infection

• Vasculitis

• Leukodystrophy

• Mitochondrial Cytopathies

• Sarcoidosis

• Histiocytic lymphangiomatosis

• Tumors / glioblastoma

• Multiple Sclerosis

 

INFECTIOUS ILLNESSES

• 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)                                    

 

IMMUNIZATIONS / VACCINATIONS

                                Rabies  

                                Diptheria -Tetnus-Pertussis

                                Hepatitis B

                                Smallpox

                                                Vaccines now devoid of neural elements

                                                Successful immunization programs, virtual eradication of                                                                                              small pox disease

ADEM Evaluation

–        CSF –        Lactate-Pyruvate –        Cytology –        IgG Index; OCB –        R/O CNS infection CSF profile, CSF viral & bacterial cultures  PCR- especially for Herpes Simplex Virus  Lyme titer Measles Ab

Blood    CBC/diff, Electrolytes, LFTs, ESR T4/TSH, B12, Biotinase ANA, Anticardiolipin Ab, Antiphospholipid Ab, ACE Lupus Anticoagulant VDRL/RPR CADASIL, LHON mutation Mitochondrial gene mutation Lactate-Pyruvate

 

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

                                        biphasic

                                        multiphasic

                                        relapsing

                                        recurrent

                                        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

 

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??

 

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

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

 

Consequences

• 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