World Library  
Flag as Inappropriate
Email this Article

Acute disseminated encephalomyelitis

Article Id: WHEBN0000000967
Reproduction Date:

Title: Acute disseminated encephalomyelitis  
Author: World Heritage Encyclopedia
Language: English
Subject: Multiple sclerosis, Transverse myelitis, Measles, Powassan virus, Subacute sclerosing panencephalitis
Collection: Autoimmune Diseases, Enterovirus-Associated Diseases, Measles, Multiple Sclerosis, Neurological Disorders
Publisher: World Heritage Encyclopedia

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis
Classification and external resources
ICD-10 G04.0
ICD-9-CM 323.61, 323.81
DiseasesDB 158
eMedicine neuro/500
MeSH D004673

Acute disseminated encephalomyelitis (ADEM) (or acute demyelinating encephalomyelitis) is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. It is often triggered after the patient has received a viral infection or vaccination.[1][2][3][4][5][6]

ADEM's symptoms resemble the symptoms of multiple sclerosis (MS), so the disease itself is sorted into the classification of the multiple sclerosis borderline diseases. However, ADEM has several features that distinguish it from MS.[7] Unlike MS, ADEM occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too. ADEM consists of a single flare-up whereas MS is marked with several flare-ups over a long period of time. ADEM is also distinguished by a loss of consciousness, coma and death, which is very rare in MS, except in severe cases.

The incidence rate is about 8 per 1,000,000 people per year.[8] Although it occurs in all ages, most reported cases are in children and adolescents, with the average age around 5 to 8 years old.[9][10][11] The mortality rate may be as high as 5%; however, full recovery is seen in 50 to 75% of cases with increase in survival rates up to 70 to 90% with figures including minor residual disability as well.[12] The average time to recover from ADEM flare-ups is one to six months.

ADEM produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum, brainstem, and spinal cord,[13] but periventricular white matter and gray matter of the cortex, thalami and basal ganglia may also be involved.

When the patient suffers more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis[14] or multiphasic disseminated encephalomyelitis[15](MDEM).


  • Causes and antecedent history 1
  • Presentation 2
  • Treatment 3
  • Prognosis 4
    • Motor deficits 4.1
    • Neurocognitive 4.2
  • Acute disseminated encephalomyelitis and multiple sclerosis 5
  • Multiphasic disseminated encephalomyelitis 6
  • Acute hemorrhagic leukoencephalitis 7
  • Experimental allergic encephalomyelitis 8
  • See also 9
  • References 10
  • External links 11

Causes and antecedent history

Viral infections thought to induce ADEM include

  • Acute Disseminated Encephalomyelitis (ADEM) at
  • Acute disseminated encephalomyelitis at NIH's Office of Rare Diseases
  • Acute Disseminated Encephalomyelitis Information Page at NINDS
  • Information for parents about Acute disseminated encephalomyelitis

External links

  1. ^
  2. ^
  3. ^
  4. ^
  5. ^
  6. ^ a b
  7. ^ Lauren B. Krupp et al. Consensus definitions proposed for pediatric multiple sclerosis and related disorders, 2007 by AAN Enterprises, Inc. [1]
  8. ^ a b
  9. ^
  10. ^ a b
  11. ^
  12. ^ a b c
  13. ^
  14. ^
  15. ^ a b c
  16. ^
  17. ^ a b c
  18. ^ a b
  19. ^
  20. ^ a b
  21. ^ a b c d e
  22. ^ a b
  23. ^
  24. ^
  25. ^
  26. ^
  27. ^
  28. ^
  29. ^
  30. ^ a b c
  31. ^ a b
  32. ^
  33. ^
  34. ^
  35. ^
  36. ^
  37. ^
  38. ^
  39. ^
  40. ^
  41. ^
  42. ^ Weinshenker B, Miller D. (1999). Multiple sclerosis: one disease or many? In: Siva A, Kesselring J, Thompson A, eds. Frontiers in multiple sclerosis. London: Dunitz, p37-46.
  43. ^
  44. ^ Lauren B. Krupp et al, Consensus definitions proposed for pediatric multiple sclerosis and related disorders. NEUROLOGY 2007;68(Suppl 2):S7–S12
  45. ^
  46. ^
  47. ^ Nathan P. Young, Acute Disseminated Encephalomyelitis: Current Understanding and Controversies. Thieme Medical Publishers (Semin Neurol. 2008 Feb;28(1):84-94) [2]
  48. ^
  49. ^
  50. ^
  51. ^ M. Baumann, E.M. Hennes, K. Schanda, M. Karenfort, B. Bajer-Kornek, K. Diepold, B. Fiedler, I. Marquardt, J. Strautmanis, S. Vieker, M. Reindl, K. Rostásy. Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies. European Journal of Paediatric Neurology, Volume 19, Supplement 1, May 2015, Pages S21, Abstracts of the 11th EPNS Congress. 22 May 2015. doi:10.1016/S1090-3798(15)30066-0
  52. ^ a b
  53. ^ a b
  54. ^ a b
  55. ^
  56. ^ Yildiz O. et al. Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis. J Neuroinflammation. 2015 Sep 17;12(1):175. doi: 10.1186/s12974-015-0398-1.
  57. ^
  58. ^


See also

Experimental allergic encephalomyelitis (EAE) is an animal model of CNS inflammation and demyelination frequently used to investigate potential MS treatments.[57] An acute monophasic illness, EAE is far more similar to ADEM than MS.[58]

Experimental allergic encephalomyelitis

This disease has been occasionally associated with ulcerative colitis and Crohn's disease, malaria,[55] septicemia associated with immune complex deposition, methanol poisoning, and other underlying conditions. Also anecdotal association with MS has been reported[56]

Acute hemorrhagic leukoencephalitis (AHL, or AHLE), also known as acute necrotizing encephalopathy (ANE), acute hemorrhagic encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, or Hurst's disease, is a hyperacute and frequently fatal form of ADEM. AHL is relatively rare (less than 100 cases have been reported in the medical literature as of 2006),[52] it is seen in about 2% of ADEM cases,[21] and is characterized by necrotizing vasculitis of venules and hemorrhage, and edema.[53] Death is common in the first week[54] and overall mortality is about 70%,[52] but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange.[17] About 70% of survivors show residual neurological deficits,[53] but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected.[54]

Acute hemorrhagic leukoencephalitis

It has been found that anti-MOG auto-antibodies are related to this kind of ADEM[51]

When the patient suffers more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis or multiphasic disseminated encephalomyelitis[15] (MDEM).

Multiphasic disseminated encephalomyelitis

Nevertheless, the co-occurrence of perivenous and confluent demyelination in some individuals suggests pathogenic overlap between acute disseminated encephalomyelitis and multiple sclerosis and misclassification even with biopsy[49] or even postmortem[50]

Plaques in the white matter in MS are sharply delineated, while the glial scar in ADEM is smooth. Axons are better preserved in ADEM lesions. Inflammation in ADEM is widely disseminated and ill-defined, and finally, lesions are strictly perivenous, while in MS they are disposed around veins, but not so sharply.[48]

The pathology of ADEM is very similar to that of MS with some differences. The pathological hallmark of ADEM is perivenular inflammation with limited ‘‘sleeves of demyelination.’’.[47]

Problems for differential diagnosis increase due to the lack of agreement for a definition of Multiple Sclerosis.[45] For some people MS should be considered a clinical entity based in inflammatory lesions separated in time and space.[46] As some cases of ADEM satisfy these conditions, they can be considered inside the clinical MS spectrum.

Normally ADEM appears in children after a vaccination and it is monophasic. Nevertheless, ADEM can appear in adults, and can also be clinically multiphasic.[44]

While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects.[41] Some authors consider MS and its borderline forms to constitute a spectrum, differing only in chronicity, severity, and clinical course,[42][43] while others consider them discretely different diseases.[6]

Acute disseminated encephalomyelitis and multiple sclerosis

Another study compared nineteen children with a history of ADEM, of which 10 were five years of age or younger at the time (average age 3.8 years old, tested an average of 3.9 years later) and nine were older (mean age 7.7y at time of ADEM, tested an average of 2.2 years later) to nineteen matched controls.[38] Scores on IQ tests and educational achievement were lower for the young onset ADEM group (average IQ 90) compared to the late onset (average IQ 100) and control groups (average IQ 106), while the late onset ADEM children scored lower on verbal processing speed. Again, all groups means were within one standard deviation of the controls, meaning that while effects were statistically reliable, the children were as a whole, still within the normal range. There were also more behavioural problems in the early onset group, although there is some suggestion that this may be due, at least in part, to the stress of hospitalization at a young age.[39][40]

Patients with demyelinating illnesses, such as MS, have shown cognitive deficits even when there is minimal physical disability.[35] Research suggests that similar effects are seen after ADEM, but that the deficits are less severe than those seen in MS. A study of six children with ADEM (mean age at presentation 7.7 years) were tested for a range of neurocognitive tests after an average of 3.5 years of recovery.[36] All six children performed in the normal range on most tests, including verbal IQ and performance IQ, but performed at least one standard deviation below age norms in at least one cognitive domain, such as complex attention (one child), short-term memory (one child) and internalizing behaviour/affect (two children). Group means for each cognitive domain were all within one standard deviation of age norms, demonstrating that, as a group, they were normal. These deficits were less severe than those seen in similar aged children with a diagnosis of MS.[37]


Residual motor deficits are estimated to remain in about 8 to 30% of cases, the range in severity from mild clumsiness to ataxia and hemiparesis.[17]

Motor deficits

Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRS or EDSS), average time to recover is one to six months.[12] The mortality rate may be as high as 5%.[12] Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes.[34] The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.


There is some evidence to suggest that patients may respond to a combination of methylprednisolone and immunoglobulins if they fail to respond to either separately[32] In a study of 16 children with ADEM, 10 recovered completely after high-dose methylprednisolone, one severe case that failed to respond to steroids recovered completely after IV Ig; the five most severe cases -with ADAM and severe peripheral neuropathy- were treated with combined high-dose methylprednisolone and immunoglobulin, two remained paraplegic, one had motor and cognitive handicaps, and two recovered.[30] A recent review of IVIg treatment of ADEM (of which the previous study formed the bulk of the cases) found that 70% of children showed complete recovery after treatment with IVIg, or IVIg plus corticosteroids.[33] A study of IVIg treatment in adults with ADEM showed that IVIg seems more effective in treating sensory and motor disturbances, while steroids seem more effective in treating impairments of cognition, consciousness and rigor.[31] This same study found one subject, a 71-year-old man who had not responded to steroids, that responded to an IVIg treatment 58 days after disease onset.

No controlled clinical trials have been conducted on ADEM treatment, but aggressive treatment aimed at rapidly reducing inflammation of the CNS is standard. The widely accepted first-line treatment is high doses of intravenous corticosteroids,[30] such as methylprednisolone or dexamethasone, followed by 3–6 weeks of gradually lower oral doses of prednisolone. Patients treated with methylprednisolone have shown better outcomes than those treated with dexamethasone.[21] Oral tapers of less than three weeks duration show a higher chance of relapsing,[10][15] and tend to show poorer outcomes. Other anti-inflammatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis, high doses of intravenous immunoglobulin (IVIg),[30][31] mitoxantrone and cyclophosphamide. These are considered alternative therapies, used when corticosteroids cannot be used, or fail to show an effect.


ADEM has an abrupt onset and a monophasic course. Symptoms usually begin 1–3 weeks after infection. Major symptoms include fever, headache, nausea and vomiting, confusion, vision impairment, drowsiness, seizures and coma. Although initially the symptoms are usually mild, they worsen rapidly over the course of hours to days, with the average time to maximum severity being about four and a half days.[21] Additional symptoms include hemiparesis, paraparesis, and cranial nerve palsies.[29]


[18] tissue, have ADEM incident rates as high as 1 in 600.CNS Some vaccines, later shown to have been contaminated with host animal [28][22] which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1000 for measles (and 1 per 5000 for rubella).[20] The risk of ADEM from measles vaccination is about 1 to 2 per million,[21]

This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.