Acute disseminated encephalomyelitis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

No one test established the diagnosis of ADEM. Supporting features include an appropriate viral or vaccination history, an appropriate acute neurologic illness, and consistent features on CNS imaging.

Differential Diagnosis

  • Acute infectious encephalitis
    • Herpes simplex virus
      • Most common and treatable form of infectious encephalitis
      • Usually due to Human herpesvirus 1 (HSV-1), though HSV-2 accounts for 5%
      • One-third occur during primary infection
      • Most commonly involves the temporal and frontal lobes; speech disorders, bizarre behaviors, and gustatory and olfactory hallucinations are common
      • Fever present in 90%. Altered state of consciousness present in most.
      • Associated with scattered hemorrhages, CSF red cells
      • Treated with acyclovir 10 mg/kg IV q8h; reduces mortality and morbidity if started early enough. Untreated mortality is 70%.
    • Epstein-Barr virus
    • Lyme disease
    • Arborviruses
      • Viruses transmitted by arthropods, mosquitos and tick
      • Most common in the summer and fall (in contrast to winter and spring presentations of measles, mumps and VZV).
      • Present with:
        • Fever
        • Headache
        • Gastrointestinal symptoms
        • Neurologic disease typically presents day 2 or 3
        • CSF typically shows elevated protein, a few hundred white blood cells, normal glucose
        • No specific treatment
    • Eastern equine encephalitis
      • Presents with flu-like symptoms, fever, headache, vomiting, seizures, and progressive neurologic disease
      • Seen mostly along the east coast of the U.S.
      • Mosquito and bird vectors
      • Most common in those <15 or >55 years of age
      • Most virulent of arborviruses: 70% mortality
    • Western equine encephalitis
      • Mosquito vector
      • Young children
      • Often asymptomatic
      • Western U.S.
    • California encephalitis
      • Worldwide
      • Most common in school-age children
      • Mosquito vector
      • Gastrointestinal (GI) symptoms common
    • St. Louis encephalitis
      • Wild bird reservoir
      • Wild bird – mosquito cycle
      • Throughout U.S.
    • Japanese encephalitis
      • Flavivirus endemic in Southeast Asia from India to Japan
      • Mosquito transmission
      • Vaccine available
    • Mycoplasma infection
    • Cytomegalovirus infection
    • Ehrlichiosis
    • Measles
    • VZV/chickenpox
    • Mumps encephalitis
      • CNS features present in ~1% of cases
      • Not all patients have parotitis
      • Most common in winter and spring
      • Most patients recover completely, but some patients left with deafness, seizure, and mental retardation
      • Confirmed via culture or serology
    • Mycoplasma
    • Bacterial meningoencephalitis
    • Other infectious encephalitidies
  • Acute multiple sclerosis (MS)
    • MS may not be possible to exclude, and to some extent depends upon the natural history of the patient’s disease; MS is typically a chronic disease with a recurrent or progressive course, and ADEM is usually an acute monophasic disease. Both diseases are characterized by demyelination; it is acute in ADEM, and sustained or progressive in MS. It is sometimes best to refer to the illness as an “acute demyelinating disease”, until the disease course declares itself.
    • Simultaneous optic nerve, brain and spinal cord involvement, as well as meningismus, drowsiness, coma and seizures, are features suggestive of ADEM instead of MS.
    • Optic nerve involvement is typically bilateral in ADEM, and unilateral in MS. Transverse myelopathy is usually complete in ADEM, and partial in MS.
    • CSF protein is usually elevated in ADEM, and is often normal in MS. CSF lymphocyte counts >50, and CSF polys are also uncommon in MS.
    • In ADEM in contrast to MS, most MRI lesions enhance with gadolinium, suggestive that all lesions are active, and that the disease is therefore monophasic.
  • Hypoxic encephalopathy
  • Cerebrovascular disease
  • CNS vasculitis
  • Lupus cerebritis
  • Toxin effect
  • Acute toxic hepatoencephalopathy – Reye’s syndrome
    • Acute liver and CNS disease in children under 15 years of age, characterized by progressive liver and CNS disease, commonly in association with the use of salicylates.
    • Often follows a viral infection, especially chickenpox or influenza.
    • Patients often present with vomiting and progressive neurologic disease. Hypoglycemia is common. Jaundice is usually not a prominent feature.
    • The liver is enlarged and evidence of liver disease includes elevated transaminases, prothrombin time, and ammonia, hypoglycemia, and metabolic acidosis. Cerebral edema and brain neuronal degeneration occurs.
    • Mitochondria dysfunction occurs in the liver, brain and muscle. Liver cells show microvacuolization, as do renal tubules.
    • Mortality approaches 50%.

References

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