eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Acute Disseminated Encephalomyelitis: Differential Diagnoses & Workup

Author: Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Contributor Information and Disclosures

Updated: Sep 3, 2009

Differential Diagnoses

Other Problems to Be Considered

Abducens (VI) nerve palsy
Adrenoleukodystrophy
Adrenomyeloneuropathy
Non-Downs atlanto-occipital instability
Chiari malformation
Behçet disease
CNS vasculitis
Echinococcosis
Hypersensitivity vasculitides
Moyamoya disease
Neuroaxonal dystrophy
Subacute sclerosing panencephalitis
Toluene encephalopathy
Toxic subacute myelopticoneuropathy

Workup

Laboratory Studies

• Platelet counts are elevated in a substantial number of children with ADEM. Sedimentation rates are occasionally mildly elevated; greater elevation suggests the possibility of vasculitis or infection.
• Modest-to-moderate elevation of CSF white and red blood cell counts may be found in childhood ADEM. Red blood cells may be due to modest degrees of AHLE. Elevated CSF HSV or Lyme titers do not exclude the possibility of associated ADEM. 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 (Rust, 1989; Rust, 1988). CSF myelin basic protein concentration, reflecting demyelination, is frequently elevated.

Imaging Studies

• The CT scan low-density abnormalities are 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.
• T2-weighted, proton-density, or echo-planar trace diffusion MRI techniques disclose high-signal lesions in more than 80-90% of cases of ADEM. Apparent diffusion coefficient maps show high-signal changes consistent with vasogenic edema.⁶ ADEM lesions are characteristically 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. They are found in less than 40% of adults initially diagnosed as having ADEM, many of whom are later diagnosed as having MS.
  • Many of the diseases that constitute the differential diagnosis of ADEM produce MRI abnormalities that emulate various ADEM-associated lesions. Some cases of encephalitis result in the development of multiple tiny or small patches of bright signal on T2-weighted images that have been mislabeled as ADEM, but response to corticosteroid therapy is poor and follow-up scans may show severe encephaloclasia. HSV2 encephalitis or Lyme disease may be difficult to distinguish from ADEM and may involve ADEM mechanisms in pathogenesis. Pial enhancement does not occur in ADEM and suggests meningoencephalitis. Metazoal parasitic diseases of the brain (eg, cysticercosis), neoplasia, and ADEM are occasionally mistaken for one another.
  • Additional lesions may be found in deeper white matter, optic nerves, basal ganglia (30-40%), the thalamus (30-40%), the brainstem (45-55%), the cerebellum (30-40%), and the spinal cord. Periventricular lesions (30-45%) and corpus callosum lesions (20-25%) are uncommon in childhood ADEM compared with MS.⁷
  • The indistinct margins of childhood ADEM lesions tend to suggest a "smudged" edge rather than the crisp margin typical of the classic ellipsoid plaques of MS.
• ADEM lesions may contain areas of hemorrhage suggestive of HSV2 encephalitis, changes never found in MS plaques. The distribution of ADEM lesions ranges from fairly symmetrical to very asymmetrical, and few if any are aligned in the Dawson finger orientation. As many as 90% of childhood ADEM lesions enhance with gadolinium. The degree of contrast enhancement of ADEM lesions is typically uniform and usually not very dense. In contrast, MS plaques tend to vary in degree of contrast enhancement and may at times enhance quite densely.^8,9,10
• MRI abnormalities may be highly suggestive of ADEM and may help greatly in distinguishing ADEM from MS or other alternative diagnoses. ADEM gives rise to a much wider variety of appearances than MS. ADEM may produce large unilateral T2 bright lesions, some of which appear to have striking central cavitation, although encephaloclasia may not be found on follow-up scanning after recovery. These lesions may suggest neoplasm, stroke, parasitism, abscess, or MS. Ring enhancement or mass effect sometimes found in ADEM may suggest abscess or tumor.¹¹ In rare cases, symmetrical, linear, posteriorly emphasized white matter changes on T2 weighting suggest leukodystrophy. Recognize that no changes on MRI are pathognomonic of ADEM or for that matter of demyelination.
• Some patients with ADEM have normal findings on MRI on initial presentation that become abnormal and characteristic of ADEM if the study is repeated several weeks later, even though patients are then showing clinical improvement.¹² This suggests that characteristic features may be missed because of sampling error, that normal findings on a scan do not exclude the ADEM diagnosis, and that the appearance of new lesions during recuperation from ADEM may not represent recrudescence of disease.¹⁰
  • Magnetization transfer MRI, single photon emission CT scanning, or nuclear magnetic resonance (NMR) spectroscopy may possibly prove helpful in distinguishing ADEM from alternative diagnoses, although the development of a pathognomonic imaging result is unlikely.
  • For these reasons, diagnosing ADEM on the basis of findings on scanning alone is dangerous. 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.
• From a retrospective analysis, Callen et al propose diagnostic criteria for MRI to distinguish a first MS attack in children from those with acute disseminated encephalomyelitis. Any 2 of the following criteria could distinguish MS from acute disseminated encephalomyelitis (sensitivity 81%, specificity 95%): (1) absence of a diffuse bilateral lesion pattern, (2) presence of black holes, and (3) presence of 2 or more periventricular lesions.⁷

Other Tests

• The EEG often exhibits disturbance of normal sleep rhythms. Focal or generalized slowing, sharp waves, rhythmic delta, or spikes may be found in the waking state during the early stages of ADEM, features that distinguish ADEM from MS. The absence of such abnormalities during the first bout of acute disseminated demyelinating illness in a child significantly increases the risk for ultimate MS diagnosis. Similar EEG abnormalities are found in adult ADEM.

Procedures

• The lumbar puncture is an essential aspect of acute disseminated encephalomyelitis (ADEM) workup.¹³ It assists in distinguishing ADEM from various forms of meningoencephalitis, especially upon the basis of titers for the various bacteria, viruses, or other agents that may produce a directly infectious form of meningoencephalitis.
  • The immune profile is also helpful in distinguishing ADEM from MS. The IgG index, IgG synthetic rate, or oligoclonal bands are positive in more than two thirds of all first clinically recognized MS bouts and in 90-98% of individuals who have experienced multiple MS bouts. One or more of these studies is positive in no more than 10% of ADEM cases.
  • Note that the findings on immune profile studies may be positive in various infectious conditions such as neurosyphilis, subacute sclerosing panencephalitis (SSPE), Lyme disease, stroke, and various forms of acute or chronic bacterial or viral meningoencephalitis. The CSF:serum IgG index or synthetic rate formulations may show positive results in neurosyphilis, Lyme disease, Guillain-Barré syndrome, some brain tumors, sarcoid, and a wide variety of bacterial or viral meningoencephalitides or other forms of CNS inflammation.
• Occasionally, brain biopsy is necessary to distinguish ADEM from other diagnostic possibilities. The diagnosis of ADEM is confirmed when typical perivenular demyelinative changes with axonal sparing are observed.

• Search for CME/CE on This Topic »

• Multiple Sclerosis (Neurology)
• Optic Neuritis, Childhood (Ophthalmology)

• British HIV Association Guidelines for Immunization of HIV-Infected Adults 2008
• Balamuthia Amebic Encephalitis -- California, 1999-2007
• Multiple Cranial Neuropathies