Guide for Nurses

Why pediatric MS is 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

Definitions

• AcuteDisseminated 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 FLAIR MRI

At onset

 

8 wk f/u

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

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 mayrecur
• 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 interferon1a (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