Imaged parent items

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

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

  • 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 MRI

At onset

8 week f/u

 

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

–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 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

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 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