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Acute disseminated encephalomyelitis


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background about Acute disseminated encephalomyelitis in pediatric patient

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Acute disseminated encephalomyelitis

  1. 1. Acute disseminated encephalomyelitis (ADEM) Dr/Reyad Alfaky
  2. 2. Demyelinating Diseases • Definition: Degeneration of previously normal myelin
  3. 3. Demyelinating Diseases A. Central nervous syetem: 1. Acute disseminated encephalomyelitis (ADEM) 2. Multiple sclerosis(MS) 3. Neuromyelitis optica(NMO) B. Peripheral nervous syetem: 1. Acute inflammatory demyelinating polyneuropathy (AIDP)
  4. 4. Definition is a demyelinating disease of the central nervous system that typically presents as 1. monophasic disorder 2. encephalopathy 3. multifocal neurologic symptoms
  5. 5. INTRODUCTION • Acute Disseminated Encephalomyelitis (ADEM) – Usually monophasic – Demyelinating disorder – Characterized by diffuse neurologic signs and symptoms (polysymptomatic) – Nuroimaging ; multifocal lesions of demyelination
  6. 6. EPIDEMIOLOGY ADEM is an uncommon illness  Mean age between 5 and 8 yr estimated incidence is 0.4/100,000 population per year Approximately three to six cases are seen each year There is no specific ethnic distribution indicate a slight male predominance A seasonal distribution has been observed showing that most ADEM cases occur in the winter and spring
  7. 7. PATHOGENESIS Most of these conditions are thought to be – caused by immune system dysregulation – triggered by an infectious or other environmental agent – genetically susceptible host.
  8. 8. PATHOGENESIS Postinfectious Postvaccinial Thought to occur from a cross reactivity in immunity to viral antigens.
  9. 9. PATHOGENESIS The immunopathological events leading to ADEM can be divided into two major phases :- 1. Initial T cell priming and activation 2. Subsequent recruitment and effector phase
  10. 10. PATHOGENESIS typically following a recent (1-2 weeks prior) viral infection or vaccination • Sites of demyelination ; 1. white matter 2. Gray matter, especially that of the basal ganglia, is also often involved 3. lesser extent, as is the spinal cord.
  11. 11. PATHOGENESIS • Large number of viruses associated with these infections ; – approximately 50-75 percent of ADEM cases – including : • Measles , Mumps, Rubella • Varicella zoster, Epstein-Barr, Cytomegalovirus • Herpes simplex, Hepatitis A, Influenza • Enterovirus infections.
  12. 12. PATHOGENESIS • Less than 5 percent of ADEM cases follow immunization. • Associated with immunization for: • Rabies, Hepatitis B, Influenza • Japanese B encephalitis • Diphtheria /Pertussis / Tetanus • Measles, Mumps , Rubella, • Pneumococcus, Polio, Smallpox, and Varicella.
  13. 13. PATHOGENESIS • measles, mumps, and rubella vaccinations are most commonly associated with post- vaccinial ADEM.
  14. 14. CLINICAL FEATURES • Initial Presentation: 1. Fever, 2. Headache, 3. Vomiting 4. meningismus
  15. 15. CLINICAL FEATURES • febrile illness occurs in 50 to 75 percent of children • Neurologic symptoms typically appear 4 to 13 days after the infection or vaccination
  16. 16. CLINICAL FEATURES • The Neurological Signs : 1. Encephalopathy , 2. multifocal neurologic deficits
  17. 17. CLINICAL FEATURES • Encephalopathy • is a characteristic feature of ADEM • usually develops rapidly.
  18. 18. CLINICAL FEATURES • Encephalopathy results in symptoms, such as: 1. Altered level of consciousness I. lethargy →coma II. Confusion III. Excessive irritability 2. Acute cognitive dysfunction 3. Behavioral changes 4. Seizures • In about ⅓ of those diagnosed
  19. 19. CLINICAL FEATURES • Other common neurologic signs of ADEM include: 1. Long tract pyramidal signs 2. Acute hemiparesis 3. Cerebellar ataxia 4. Cranial neuropathies 5. cranial neuropathies including optic neuritis 6. spinal cord dysfunction (transverse myelitis)
  20. 20. CLINICAL FEATURES • less commonneurologic signs of ADEM include: 1. Aphasia 2. movement disorders 3. sensory deficits
  21. 21. CLINICAL FEATURES • New clinical symptoms may develop during hospitalization. • Progression of neurologic signs to maximum deficits usually occurs over four to seven days
  22. 22. CLINICAL FEATURES ; optic neuritis • Symptoms of optic neuritis include 1. vision loss 2. pain with eye movement 3. afferent pupillary defect.
  23. 23. CLINICAL FEATURES Transverse Myelitis • Symptoms of transverse myelitis include 1. flaccid paralysis of the legs 2. sensory level on examination. • The arms can be involved if the demyelinating lesion is in the cervical cord. • Respiratory failure may occur with high cervical lesions that extend into the brainstem. – Bowel and bladder involvement secondary to spinal cord disease results in constipation and urinary retention
  24. 24. Clinical course • The severe phase of ADEM typically lasts from two to four weeks. • Children may deteriorate after hospital admission – many develop new neurologic signs. • Patients usually recover completely from the acute illness – although some have neurologic sequelae.
  25. 25. hyperacute variants of ADEM  Inflammatory hemorrhagic demyelination of central nervous system white matter is seen in rare conditions that are considered to be hyperacute variants of ADEM
  26. 26. hyperacute variants of ADEM o These include: 1.Acute hemorrhagic leukoencephalitis (AHL) 2.Acute hemorrhagic encephalomyelitis (AHEM) 3.Acute necrotizing hemorrhagic leukoencephalitis (ANHLE) of Weston Hurst
  27. 27. Acute hemorrhagic leukoencephalitis • These hemorrhagic variants are more rapidly progressive and more severe than typical ADEM. • symptomatology is similar to ADEM, with meningismus, headache, seizures, multifocal neurologic signs, asymmetrical neurologic deficits, and coma. • They typically follow an upper respiratory infection. (similar to ADEM)
  28. 28. Brain imaging with MRI Acute hemorrhagic leukoencephalitis o diffuse white matter lesions, often large o associated with cerebral edema
  29. 29. Brain imaging with MRI Acute hemorrhagic leukoencephalitis o hemorrhage itself is not necessarily seen with conventional T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences. o spin-echo MRI sequences are more readily able to identify the acute hemorrhage associated with this form of ADEM.
  30. 30. Acute hemorrhagic leukoencephalitis • Some patients recover with treatment. • However, the prognosis for survival and recovery of neurologic function is worse for AHL than ADEM.
  31. 31. Laboratory studies • nonspecific findings of inflammation. – Leukocytosis is common, occurring in up to two-thirds of patients • predominantly ; lymphocytosis – Platelet counts are elevated in a number of children with ADEM. – C-reactive protein concentration may be increased. – Sedimentation rates are elevated in a third of patients
  32. 32. Investigation • Investigation for infectious agents usually includes – viral cultures of the throat and nasopharynx, stool, and CSF – serologic testing for a variety of agents, including influenza, Epstein- Barr virus, herpes, varicella, mycoplasma, cytomegalovirus, and rubella. – These studies are rarely positive
  33. 33. The cerebrospinal fluid • The cerebrospinal fluid typically shows both ; – Cerebrospinal fluid (CSF) is abnormal in about two-thirds of patients – CSF can also be normal • Evidence of inflammation 1. white and red blood cells 2. increased protein concentration 3. increase in myelin basic protein. • CSF myelin basic protein concentration level, reflecting demyelination, is frequently elevated in ADEM.
  34. 34. Lumbar puncture • Some patients with ADEM have oligoclonal bands in CSF. • Oligoclonal bands – are a nonspecific finding more often associated with multiple sclerosis; – they may also occur in 1. chronic central nervous system infections 2. viral syndromes 3. neuropathies.
  35. 35. The cerebrospinal fluid • Results of CSF immune profile testing (eg, CSF:serum immunoglobulin G [IgG] index, CNS IgG synthetic rate, oligoclonality) employing age-appropriate normative data are positive in fewer than 10% of prepubertal children with ADEM
  36. 36. The MRI abnormalities • The MRI abnormalities are best defined by 1. T2-weighted images 2. fluid-attenuated inversion recovery (FLAIR) sequences 3. proton-density, or echo-planar trace diffusion MRI techniques – characteristic high-signal lesions in virtually all cases of ADEM
  37. 37. The MRI abnormalities • The MRI abnormalities – Contrast enhancement is seen at times in acute lesions. • Findings may progress over a relatively short period of time, consistent with evolution of the disease process. • show high-signal changes consistent with vasogenic edema.
  38. 38. MRI abnormalities • Abnormalities on MRI vary in location. • Lesions associated with ADEM are 1. typically bilateral 2. asymmetric 3. poorly marginated. • Almost all patients have multiple lesions in the deep and subcortical white matter, characteristic of demyelination. • The periventricular white matter is often spared.
  39. 39. MRI abnormalities • Typical lesions of ADEM include – centrifugal at the junction of the deep cortical gray and subcortical white matter. – Such lesions are found in more than 90% of children with ADEM.
  40. 40. MRI abnormalities • Additional lesions may be found in – deeper white matter, basal ganglia (30-40%), – thalamus (30-40%), – brainstem (45-55%), – cerebellum (30-40%), – spinal cord (16-28%).
  41. 41. MRI abnormalities • Periventricular lesions and corpus callosal lesions are uncommon in childhood ADEM compared with MS
  42. 42. MRI abnormalities • Diagnosis of ADEM – should always rest on clinical grounds in children as in adults. – Radiographic studies and other laboratory tests are especially valuable in ruling in or out alternative diagnoses.
  43. 43. An Axial MRI of the brain and a saggital MRI of the spine of a patient with acute disseminated encephalomyelitis (ADEM)
  44. 44. MRI abnormalities • Brainstem and spinal cord abnormalities on MRI are common in ADEM • spinal cord, large confluent intramedullary lesions that extend over multiple segments are typical – Enhancement is variable.
  45. 45. Seven-year-old boy with acute disseminated encephalomyelitis (ADEM)
  46. 46. MRI • Magnetization transfer – may help distinguish ADEM from MS, in that normal appearing brain (on T2 weighted images) has normal magnetization transfer ratio (MTR) and normal diffusivity, – whereas in MS both measurements are significantly decreased
  47. 47. CT • The CT scan – low-density abnormalities – found in more than half of childhood or adolescent ADEM cases – but this technique is far less sensitive than MRI for the disclosure of extent and number of lesions.
  48. 48. electroencephalogram (EEG) • The electroencephalogram (EEG) is not diagnostic – It may show background slow wave activity that is typical of an encephalopathy – Seizure activity is seen.
  49. 49. visual-evoked potentials • In patients with optic neuritis, visual-evoked potentials may be prolonged.
  50. 50. DIAGNOSIS • The diagnosis of ADEM is based upon the 1. clinical 2. radiologic features – There is no specific biologic marker or confirmatory test.
  51. 51. DIAGNOSIS • An ADEM diagnosis :is considered when – individuals develop multifocal neurologic abnormalities with: 1. Confusion 2. Excessive irritability 3. Altered level of consciousness (encephalopathy) • Especially if the onset of symptoms occurs within 1 to 2 weeks after a viral/bacterial infection or a vaccination
  52. 52. DIAGNOSIS • Encephalopathy is a required feature for the diagnosis of ADEM, – but is not a typical feature of multiple sclerosis. • cerebrospinal fluid pleocytosis ≥50 white blood cells/mm can be observed in ADEM, – whereas this finding is highly atypical for multiple sclerosis.
  53. 53. DIAGNOSIS • Bacterial and viral meningitis or encephalitis must be considered and ruled out. • Empiric treatment with broad-spectrum antibiotics and acyclovir should be considered until an infectious etiology is excluded
  54. 54. Diagnostic Criteria for Pediatric ADEM (All Required)
  55. 55. Characteristic Patterns on MRI
  56. 56. Multiphasic ADEM • Individuals who have experienced typical ADEM are at risk for recurrence. – As many as 10% of children with an initial diagnosis of ADEM experience another ADEM attack – typically within the first 2-8 years after the initial attack.
  57. 57. Monophasic ADEM 1. A single clinical episode of ADEM may evolve over as long as three months 2. Any new and fluctuating symptoms occurring within three months of the initial event 3. symptoms that appear during glucocorticoid taper or 4. within one month of completing a glucocorticoid taper
  58. 58. Recurrent And Multiphasic ADEM • Recurrent ADEM and multiphasic ADEM are the two relapsing forms of the disease. 1. more than three months after the initial event and 2. more than one month after completion of glucocorticoids. – By definition for ADEM, both must include a clinical presentation with encephalopathy.
  59. 59. Recurrent ADEM 1. three or more months after the first ADEM event 2. same symptoms that occurred at the time of the initial presentation. 3. The MRI findings are also similar to the initial event and are without new lesions, – although there may be enlargement of the original lesions.
  60. 60. Multiphasic ADEM 1. recurrent disease that meets criteria for ADEM but involves new anatomic areas of the central nervous system. 2. Symptoms and neuroimaging findings are different from the initial event, with the exception that symptoms and signs of encephalopathy may not differ from the initial episode. 3. The MRI must show new lesions compared with the first attack and demonstrate complete or partial resolution of the lesions associated with the first ADEM episode.
  61. 61. Differential Diagnosis • other inflammatory demyelinating disorders should be considered. These include: 1. Multiple sclerosis 2. Optic neuritis 3. Transverse myelitis 4. Neuromyelitis optica (Devic's disease) 5. Other rare conditions
  62. 62. Differential diagnosis 1. CNS Infection: Acute bacterial or viral infections 2. Mitochondrial disease 3. Leukodystrophies: Metachromatic leukodystrophy, X-linked adrenoleukodystrophy, Alexander's disease 4. Vitamin deficiency B12, folate 5. CNS malignancy: Lymphoma, high grade glioma 6. Granulomatous diseases Neurosarcoidosis, Wegener's granulomatosis 7. Inflammatory disease ADEM/MDEM, SLE, Antiphospholipid antibody syndrome, Sjogren's disease, Behcet's disease
  63. 63. Diagnosis of demyelinating clinical event ADEM: acute disseminated encephalomyelitis MDEM: multiphase ADEM CIS: clinically isolated syndrome MS: multiple sclerosis NMO: neuromyelitis optica ON: optic neuritis TM: transverse myelitis
  64. 64. MRI algorithm
  65. 65. TREATMENT • It is important to first consider a treatment with antibiotics and/or acyclovir until an infectious cause is ruled out • A high dose of intravenous corticosteroids, for 3-5 days is the primary and most common first treatment of ADEM
  66. 66. TREATMENT 1. high-dose intravenous (IV) glucocorticoids. 2. intravenous immune globulin 3. plasma exchange
  67. 67. ADEM: Treatment • High Dose Steroids – High dose IV Methyl Prednisolone 30 mg/kg/day for 3-5 days • IVIG (<1 yr, No improvement in 48-72 hrs , AHLE, Recurrent) – 1 gm/kg/day iv for 2 days • Plasmapheresis • Symptomatic Rx
  68. 68. TREATMENT • For children with ADEM, we recommend immunosuppressive treatment • We suggest initial therapy with high-dose glucocorticoids • IV methylprednisolone (30 mg/kg per day, up to a maximum dose of 1000 mg per day) for five days without a taper.
  69. 69. TREATMENT • For children with ADEM who have an insufficient response to IV glucocorticoid treatment, we suggest intravenous immune globulin treatment • For children with ADEM who do not respond to glucocorticoids and IVIG, we suggest treatment with plasma exchange
  70. 70. PROGNOSIS • Prognosis for most children with ADEM is good • Recovery is usually a slow process lasting from four to six weeks • The majority of children with ADEM make a full recovery
  71. 71. PROGNOSIS • Between 60 to 90 percent are left with no neurological deficits • Those children who do have residual symptoms are reported to have symptoms from: • Transverse myelitis • Recurrent headaches • Behavioral problems
  72. 72. PROGNOSIS • Long-term clinical follow-up and sequential imaging by MRI are normally required to confirm a diagnosis of ADEM.
  73. 73. PROGNOSIS • Development of a relapse with new lesions, it is not compatible with a diagnosis of monophasic ADEM
  74. 74. PROGNOSIS • Depending on the clinical and imaging features, it likely suggests the correct diagnosis being either multiphasic ADEM or MS.
  75. 75. PROGNOSIS • Depending on the clinical and imaging features, it likely suggests the correct diagnosis being either multiphasic ADEM or MS.
  76. 76. PROGNOSIS • The prognosis for survival and recovery of neurologic function is worse for the hyperacute hemorrhage variants of ADEM, such as acute hemorrhagic leukoencephalitis, than for typical ADEM
  77. 77. PROGNOSIS • Complete recovery in 10 (77%) of the survivors • Relapsing disease in 2 (15%) • Mortality less than 2% – fulminant cervical transverse myelitis or brain swelling. Children younger than 2 years
  78. 78. • Acute disseminated encephalomyelitis • Presents with – Altered mental status/encephalopathy (irritability to obtunded) – Acute/subacute onset of focal symptoms based on lesions (max neuro symptoms over 4-7 days) – Typically still during febrile illness (typically URI) – 1/3 with seizures • Workup – Labs: none are diagnostic – CSF: pleocytosis, elevated protein, elevated IgG index; rule out infection! – Imaging: MRIbrain with contrast • Treatment: IV steroids (ok to start while r/o infection and prophylactic antibiotics are on board) > IVIg > PLEX; PT • Outcome – Recovery over 4-6 weeks- 60-90% with no residual defecits – Repeat MRI 6-12 months later to assess for lesion resolution