ADEM

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ADEM

• Dr Rajesh Kumar
• MD (PGI), DM (Neonatology) PGI, Chandigarh, India
• Rani Children Hospital, Ranchi

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Acute Disseminated Encephalomyelitis

• Inflammatory, nonvasculitic, demyelinating,
  immune mediated, monophasic and polysymptomatic
  disease of the central nervous system
• Post infectious encephalomyelitis,
• Post vaccination encephalomyelitis

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• 5 ½ years FCH, had pain abdomen, fever 7 days
  back
• Had dystonia, aphasia, seizure one episode
• Developed fever next day
• On examination no neurodeficit
• CT
• MRI

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• 8 years old FCH
• Sudden onset of loss of vision
• Headache
• Afebrile
• MRI normal
• Eye B/L Pappilitis
• Treated with 3 days IV methylpred, good recovery

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Post infectious CNS illness

• Acute cerebellar syndrome 1 in 1000
• Sensorineural deafness after mumps
• Sydenhams chorea
• Inflammatory lesion at single site optic
  neuritis, transverse myelitis
• Disseminated inflammatory CNS disease ADEM,
  MDEM, MS

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History

• Why should we know now
• Increase in vaccinations
• Post ADEM may have long term disability
• Highly effective treatment is available now

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ADEM Pathology
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Pathology

• Resembles pathology of experimental allergic
  encephalomyelitis (EAE).
• Prominence of perivenular round cell inflammation
  (found in many encephalitis)
• Patchy demyelination with preservation of axon
  cylinders and the prominence of microglial cells
  in the inflammatory exudate (these are not found
  in encephalitis. )

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Epidemiology

• Incidence 0.8 per 100,000, FgtM
• 80 of childhood cases occur lt 10 years, even at
  4 months
• 2 weeks post infection (range 2-20 days)
  (antigenic triggering)
• Post exanthematous fever ADEM 100100,000 after
  measles in one series
• Post vaccine meales, MMR, Rubella, influnzae,
  rabies, Jap B encephalitis
• measles vaccinationassociated ADEM is about 10
  to 20 per 100 000
• Vaccine assoiated ADEM upto 3 months post
  vaccination WHO guidline

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Spectrum of demyelinating disease

• Optic neuritis ---- ADEM ------- MS
• Division between these processes is indistinct
• Other boundaries of ADEM merge indistinctly with
  a wide variety of inflammatory encephalitic and
  vasculitic illnesses as well as monosymptomatic
  postinfectious illnesses that should remain
  distinct from ADEM, such as acute cerebellar
  ataxia (ACA).
• A further indistinct boundary is shared by ADEM
  and Guillain-Barré syndrome and is manifested in
  cases of Miller-Fisher syndrome and
  encephalomyeloradiculoneuropathy (EMRN).

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Pathogenesis (Two concepts)

• Molecular mimickery brain vaccines
• Th2 lymphocytes have increased reactivity to
  myelin basic protein
• Inflammatory cascade concept
• CNS infections triggering immune response, damage
  to BBB, brain specific antigens spills into
  systemic circulation and initiates immunologic
  process

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Clinical features

• Prodromal illness ? asymptomatic period ? acute
  neurological presentation
• Neurological onset is abrupt (gt95 cases)
• Mental changes are common (gt85 cases)
• Convulsive seizure in gt25 cases
• Optic Neuritis, Cranial nerve abnormality
• Long tract signs in gt85 cases

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ADEM Clinical Syndromes

• Mild encephalopathy, sometimes associated with
  long tract signs
• Severe encephalopathy with bilateral paresis,
  often associated with brainstem signs,
  particularly the lower cranial nerves
• Predominantly brainstem presentation with
  features suggesting Fisher syndrome in some cases
  or Bickerstaff brainstem encephalitis in other
  cases
• Hemiparesis, ipsilateral long tract signs, with
  or without seizure
• Predominantly ataxic, differing from the
  predominantly axial/gait ACA in that
  ADEM-associated ataxia is often associated with
  nystagmus, extremity ataxia, and long tract signs
  
• EMRN (mixed upper and lower motor neuron signs)

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Clinical presentation

• The age at onset ranged from 4 months to 15
  years. Seventeen (85) children had a recent
  infectious prodrome. Children presented most
  often with acute consciousness disturbance (70)
  and motor deficits (55). Seizures occurred in 10
  (50), Acta Paediatr Taiwan. 2006
• Mean age at onset was 5.3 /- 3.9 years, with a
  significant male predominance. Sixty-two patients
  (74) had a preceding viral illness or
  vaccination. Acute hemiparesis (76), unilateral
  or bilateral long tract signs (85), and changes
  in mental state (69) were the most prominent
  presenting features Neurology. 2002

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Fulminant ADEM

• In children lt3yrs
• Rapid evolution of a low state of function and
  demonstration on scans of severe edema.
• Transverse myelitis may begin rapidly and be
  associated with severe edema, usually in the
  cervical region

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Physical Signs

• Irritability and lethargy
• Fever (50),headache (45-65) and meningism
  (20-30)
• Development of neurologic abnormalities minutes
  to 6 weeks or more.
• Neurological abnormality visual disturbances and
  language, mental status, and psychiatric
  abnormalities
• Weakness (50-75 of cases) is more commonly
  discerned than sensory defects (15-20).

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Triad of ADEM

• Prodromal illness or preceding vaccination,
• MRI signs of demyelination,
• Acute presentation of neurologic symptoms

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Lab

• Leukocytosis with lymphopenia, increased
  platelet, Mild elevation in ESR
• CSF may show inflammatory rsults
• EEG may be abnormal
• VEP, BERA may be abnormal

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Neuroimaging

• MRI extensive, multifocal, subcortical white
  matter abnormalities
• MRI subcortical white matter, may be gray matter
  also,
• CT may be normal in 50 cases
• Convalescent MRI helpful in deffrentating with
  MS, new lesions in MS

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Treatment

• IV methylprednisolone (20-30 mg/kg) for 3-5 days
  followed by oral prednisolone for 2-6 weeks
• Longer the course fewer the relapse
• IVIG, Plasmapharesis
• Cyclosporin , cyclophosphamide
• Methylpred IVIG

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• Relapse within 6 months MDEM
• Relapse after 6 months MS
• Vaccination should be avoided within 6 months of
  ADEM

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Prognosis

• Mortality 10 in older studies, Now lt2
• Morbidity visual, motor, autonomic, and
  intellectual deficits and epilepsy.
• Problems persist after the first few weeks of
  illness in only about 35 of cases, and in most
  of these patients, the deficits resolve within 1
  year of onset.
• Intellectual deficits (varying from attention
  problems to mental retardation) and epilepsy
  arise most often in children whose bout of ADEM
  occurs before the second birthday.
• Visual and motor deficits and problems with bowel
  or bladder function may persist for varying
  periods of time

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Follow up

• The long-term (10-y follow-up) risk of patients
  with ADEM for development of MS is 25.
• Risk for MS is highest in children whose ADEM
  onset was
• (1) afebrile,
• (2) without mental status change,
• (3) without prodromal viral illness or
  immunization,
• (4) without generalized EEG slowing,
• (5) associated with an abnormal CSF immune
  profile

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