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Journal of Neurology

, Volume 262, Issue 9, pp 2013–2024 | Cite as

Acute disseminated encephalomyelitis: current controversies in diagnosis and outcome

  • Diederik L. H. Koelman
  • Farrah J. Mateen
Review

Abstract

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory, demyelinating disorder of the CNS. Only in the past 15 years have larger groups of patients from several geographical areas been reported for comparisons across studies. In spite of the increased recognition of ADEM, the diagnosis of ADEM remains clinical, aided by neuroimaging confirmation, because of the lack of a biological marker. The diagnosis may be difficult, given that several diseases may present similar to ADEM. The controversial existence of multiphasic forms necessitates a continuous evaluation of the diagnosis by tracking subsequent events. Despite proposed consensus criteria, the diagnostic criteria employed to characterize ADEM range widely among the largest reported cohorts to date. This review comprehensively evaluates the current knowledge and controversies that surround ADEM, with special consideration of the distinction between ADEM and other demyelinating diseases such as multiple sclerosis. In addition, we present implications of the current knowledge of ADEM for both research and clinical practice.

Keywords

Acute disseminated encephalomyelitis Autoimmune diseases Encephalopathy Postinfectious 

Notes

Acknowledgments

We would like to thank Prof. Dr. E. T. Hedley-Whyte, Department of Pathology, Massachusetts General Hospital, for reviewing and photographing the pathology images of patients with ADEM seen in Fig. 1.

Conflicts of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Clifton F (1724) Dissertatio Medica Inauguralis; de Distinctis et Confluentibus Variolis. section IXGoogle Scholar
  2. 2.
    Brinar VV (2004) Non-MS recurrent demyelinating diseases. Clin Neurol Neurosurg 106:197–210CrossRefPubMedGoogle Scholar
  3. 3.
    Anton G, Wohlwill F (1912) Multiple nicht eitrige enzephalomyelitis und multiple sklerose. Z Gesamte Neurol Psy 12:31–98CrossRefGoogle Scholar
  4. 4.
    Koprowski H (1962) The role of hyperergy in measles encephalitis. Am J Dis Child 103:273–278PubMedGoogle Scholar
  5. 5.
    Pohl D, Hennemuth I, von Kries R, Hanefeld F (2007) Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr 166:405–412CrossRefPubMedGoogle Scholar
  6. 6.
    Leake JAD, Albani S, Kao AS et al (2004) Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 23:756–764CrossRefPubMedGoogle Scholar
  7. 7.
    Banwell B, Kennedy J, Sadovnick D et al (2009) Incidence of acquired demyelination of the CNS in Canadian children. Neurology 72:232–239CrossRefPubMedGoogle Scholar
  8. 8.
    Torisu H, Kira R, Ishizaki Y et al (2010) Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan. Brain Dev 32:454–462CrossRefPubMedGoogle Scholar
  9. 9.
    Hung K-L, Liao H-T, Tsai M-L (2001) The spectrum of postinfectious encephalomyelitis. Brain Dev 23:42–45CrossRefPubMedGoogle Scholar
  10. 10.
    Tenembaum S, Chamoles N, Fejerman N (2002) Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology 59:1224–1231CrossRefPubMedGoogle Scholar
  11. 11.
    Idrissova ZR, Boldyreva MN, Dekonenko EP et al (2003) Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol 10:537–546CrossRefPubMedGoogle Scholar
  12. 12.
    Singhi PD, Ray M, Singhi S, Khandelwal NK (2006) Acute disseminated encephalomyelitis in North Indian children: clinical profile and follow-up. J Child Neurol 21:851–857CrossRefPubMedGoogle Scholar
  13. 13.
    Mikaeloff Y, Caridade G, Husson B et al (2007) Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse. Eur J Paediatr Neurol 11:90–95CrossRefPubMedGoogle Scholar
  14. 14.
    De Seze J, Debouverie M, Zephir H (2007) Acute fulminant demyelinating disease. Arch Neurol 64:1426–1432CrossRefPubMedGoogle Scholar
  15. 15.
    Panicker JN, Nagaraja D, Kovoor JME, Subbakrishna DK (2010) Descriptive study of acute disseminated encephalomyelitis and evaluation of functional outcome predictors. J Postgrad Med 56:12–16CrossRefPubMedGoogle Scholar
  16. 16.
    Ketelslegers IA, Visser IER, Neuteboom RF et al (2011) Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children. Mult Scler 17:441–448CrossRefPubMedGoogle Scholar
  17. 17.
    Marchioni E, Ravaglia S, Montomoli C (2013) Postinfectious neurologic syndromes: a prospective cohort study. Neurology 80:882–889CrossRefPubMedGoogle Scholar
  18. 18.
    Bonaccorsi A, Garattine S, Jori A (1964) Neurological complications of smallpox vaccination. Br Med J 2:1345–1347CrossRefPubMedGoogle Scholar
  19. 19.
    Behan PO (2009) Acute disseminated encephalomyelitis: postinfectious, postimmunization and variant forms. Expert Rev Neurother 9:1321–1329CrossRefPubMedGoogle Scholar
  20. 20.
    Langer-Gould A, Zhang J, Chung J et al (2011) Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children. Neurology 77:1143–1148PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Dale RC, de Sousa C, Chong WK et al (2000) Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 123:2407–2422CrossRefPubMedGoogle Scholar
  22. 22.
    Murthy SNK, Faden HS, Cohen ME, Bakshi R (2002) Acute Disseminated Encephalomyelitis in Children. Pediatrics 110:e21CrossRefPubMedGoogle Scholar
  23. 23.
    Erol I, Ozkale Y, Alkan O, Alehan F (2013) Acute disseminated encephalomyelitis in children and adolescents: a single center experience. Pediatr Neurol 49:266–273CrossRefPubMedGoogle Scholar
  24. 24.
    Tenembaum SN (2013) Acute disseminated encephalomyelitis. Handb Clin Neurol 112:1253–1262CrossRefPubMedGoogle Scholar
  25. 25.
    Lucas J (1790) An account of uncommon symptoms succeeding the measles with additional remarks on the infection of measles and smallpox. London Med J 11:325–331Google Scholar
  26. 26.
    Krupp LB, Tardieu M, Amato MP et al (2013) International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 19:1261–1267CrossRefPubMedGoogle Scholar
  27. 27.
    Caldemeyer KS, Harris TM, Smith RR, Edwards MK (1991) Gadolinium enhancement in acute disseminated encephalomyelitis. J Comput Assist Tomogr 15:673–675CrossRefPubMedGoogle Scholar
  28. 28.
    Baum PA, Barkovich AJ, Koch TK, Berg B (1992) Deep gray matter involvement in children with acute disseminated encephalomyelitis. Am J Neuroradiol 15:1275–1283Google Scholar
  29. 29.
    Lakhan SE (2012) Section editor teaching neuro images: MRI time lag with acute disseminated encephalomyelitis. Neurology e138–e139Google Scholar
  30. 30.
    Khurana DS, Melvin JJ, Kothare SV et al (2005) Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis. Pediatrics 116:431–436CrossRefPubMedGoogle Scholar
  31. 31.
    Chitnis T (2013) Pediatric demyelinating diseases. Continuum 19:1023–1045Google Scholar
  32. 32.
    Sejvar JJ, Kohl KS, Bilynsky R et al (2007) Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 25:5771–5792CrossRefPubMedGoogle Scholar
  33. 33.
    Pohl D, Tenembaum SN (2012) Treatment of acute disseminated encephalomyelitis. Curr Treat Options Neurol 14:264–275CrossRefPubMedGoogle Scholar
  34. 34.
    Keegan M, Pineda AA, McClelland RL et al (2002) Plasma exchange for severe attacks of CNS demyelination : predictors of response. Neurology 58:143–146CrossRefPubMedGoogle Scholar
  35. 35.
    Marchioni E, Ravaglia S, Piccolo G et al (2005) Postinfectious inflammatory disorders: subgroups based on prospective follow-up. Neurology 65:1057–1065CrossRefPubMedGoogle Scholar
  36. 36.
    Absoud M, Parslow RC, Wassmer E et al (2011) Severe acute disseminated encephalomyelitis: a paediatric intensive care population-based study. Mult Scler 17:1258–1261CrossRefPubMedGoogle Scholar
  37. 37.
    Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Banwell B, Bar-Or A, Arnold DL et al (2011) Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol 10:436–445CrossRefPubMedGoogle Scholar
  39. 39.
    Banwell B, Krupp L, Kennedy J et al (2007) Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. Lancet Neurol 6:773–781CrossRefPubMedGoogle Scholar
  40. 40.
    Banwell BL (2004) Pediatric multiple sclerosis. Curr Neurol Neurosci Rep 4:245–252CrossRefPubMedGoogle Scholar
  41. 41.
    Marrie RA, Wolfson C, Sturkenboom MCJM et al (2000) Multiple sclerosis and antecedent infections: a case-control study. Neurology 54:2307–2310CrossRefPubMedGoogle Scholar
  42. 42.
    Schwarz S, Mohr A, Knauth M et al (2001) Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology 56:1313–1318CrossRefPubMedGoogle Scholar
  43. 43.
    Neuteboom RF, Boon M, Catsman Berrevoets CE et al (2008) Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 71:967–973CrossRefPubMedGoogle Scholar
  44. 44.
    Kesselring J, Miller DH, Robb SA et al (1990) Acute disseminated encephalomyelitis; mri findings and the distiction from multiple sclerosis. Brain J Neurol 113:291–302CrossRefGoogle Scholar
  45. 45.
    Absoud M, Lim MJ, Appleton R et al (2014) Paediatric neuromyelitis optica: clinical, MRI of the brain and prognostic features. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2014-308550 Google Scholar
  46. 46.
    Okumura A, Nakazawa M, Igarashi A et al (2014) Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis. Brain Dev 37:339–343CrossRefPubMedGoogle Scholar
  47. 47.
    Cheng C, Jiang Y, Chen X et al (2013) Clinical, radiographic characteristics and immunomodulating changes in neuromyelitis optica with extensive brain lesions. BMC Neurol 13:72PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Saiki S, Ueno Y, Moritani T et al (2009) Extensive hemispheric lesions with radiological evidence of blood-brain barrier integrity in a patient with neuromyelitis optica. J Neurol Sci 284:217–219CrossRefPubMedGoogle Scholar
  49. 49.
    Eichel R, Meiner Z, Abramsky O, Gotkine M (2008) Acute disseminating encephalomyelitis in neuromyelitis optica: closing the floodgates. Arch Neurol 65:267–271CrossRefPubMedGoogle Scholar
  50. 50.
    Beyer AM, Wandinger KP, Siebert E et al (2007) Neuromyelitis optica in a patient with an early onset demyelinating episode: clinical and autoantibody findings. Clin Neurol Neurosurg 109:926–930CrossRefPubMedGoogle Scholar
  51. 51.
    Alper G, Heyman R, Wang L (2009) Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol 51:480–486PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Neuteboom RF, Ketelslegers IA, Boon M et al (2010) Barkhof magnetic resonance imaging criteria predict early relapse in pediatric multiple sclerosis. Pediatr Neurol 42:53–55CrossRefPubMedGoogle Scholar
  53. 53.
    Verhey LH, Branson HM, Shroff MM et al (2011) MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. Lancet Neurol 10:1065–1073CrossRefPubMedGoogle Scholar
  54. 54.
    Callen DJA, Shroff MM, Branson HM et al (2009) Role of MRI in the differentiation of ADEM from MS in children. Neurology 72:968–973CrossRefPubMedGoogle Scholar
  55. 55.
    Mikaeloff Y, Adamsbaum C, Husson B et al (2004) MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 127:1942–1947CrossRefPubMedGoogle Scholar
  56. 56.
    Zhang L, Wu A, Zhang B et al (2014) Comparison of deep gray matter lesions on magnetic resonance imaging among adults with acute disseminated encephalomyelitis, multiple sclerosis, and neuromyelitis optica. Mult Scler 20:418–423CrossRefPubMedGoogle Scholar
  57. 57.
    Lu Z, Zhang B, Qiu W et al (2011) Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis. PLoS One 6:e22766PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Vishwas MS, Healy BC, Pienaar R et al (2013) Diffusion tensor analysis of pediatric multiple sclerosis and clinically isolated syndromes. Am J Neuroradiol 34:417–423CrossRefPubMedGoogle Scholar
  59. 59.
    Absoud M, Lim MJ, Chong WK et al (2013) Paediatric acquired demyelinating syndromes: incidence, clinical and magnetic resonance imaging features. Mult Scler 19:76–86PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Pohl D, Rostasy K, Reiber H, Hanefeld F (2004) CSF characteristics in early-onset. Neurology 1966–1967Google Scholar
  61. 61.
    Young NP, Weinshenker BG, Parisi JE et al (2010) Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain a J Neurol 133:333–348CrossRefGoogle Scholar
  62. 62.
    Tsai M-L, Hung K-L (1996) Multiphasic disseminated encephalomyelitis mimicking multiple sclerosis. Brain Dev 18:412–414CrossRefPubMedGoogle Scholar
  63. 63.
    Mikaeloff Y, Suissa S, Vallée L et al (2004) First epidose of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr 144:246–252CrossRefPubMedGoogle Scholar
  64. 64.
    Fridinger SE, Alper G (2013) Defining Encephalopathy in Acute Disseminated Encephalomyelitis. J Child Neurol 29:751–755CrossRefPubMedGoogle Scholar
  65. 65.
    Waldman AT, Gorman MP, Rensel MR et al (2011) Management of pediatric central nervous system demyelinating disorders: consensus of United States neurologists. J Child Neurol 26:675–682PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Alper G, Sreedher G, Zuccoli G (2013) Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not? Am J Neuroradiol 34:217–220CrossRefPubMedGoogle Scholar
  67. 67.
    Dale RC, Pillai SC (2007) Early relapse risk after a first CNS inflammatory demyelination episode: examining international consensus definitions. Dev Med Child Neurol 887–893Google Scholar
  68. 68.
    Peche SS, Alshekhlee A, Kelly J et al (2013) A long-term follow-up study using IPMSSG criteria in children with CNS demyelination. Pediatr Neurol 49:329–334CrossRefPubMedGoogle Scholar
  69. 69.
    Visudtibhan A, Tuntiyathorn L, Vaewpanich J et al (2010) Acute disseminated encephalomyelitis: a 10-year cohort study in Thai children. Eur J Paediatr Neurol 14:513–518CrossRefPubMedGoogle Scholar
  70. 70.
    Ketelslegers IA, Neuteboom RF, Boon M et al (2010) A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology 74:1412–1415CrossRefPubMedGoogle Scholar
  71. 71.
    O’Connor KC, McLaughlin KA, De Jager PL et al (2007) Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med 13:211–217PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Van Haren K, Tomooka BH, Kidd BA et al (2013) Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis. Mult Scler 19:1726–1733PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Di Pauli F, Mader S, Rostasy K et al (2011) Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol 138:247–254CrossRefPubMedGoogle Scholar
  74. 74.
    Brilot F, Dale RC, Selter RC et al (2009) Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol 66:833–842CrossRefPubMedGoogle Scholar
  75. 75.
    Baumann M, Sahin K, Lechner C et al (2014) Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2014-308346 Google Scholar
  76. 76.
    Probstel A, Downmair K, Bittner R, et al. (2011) Antibodies to MOG are transient in childhood acute disseminated encephalomyelitisGoogle Scholar
  77. 77.
    Lalive PH, Häusler MG, Maurey H et al (2011) Highly reactive anti-myelin oligodendrocyte glycoprotein antibodies differentiate demyelinating diseases from viral encephalitis in children. Mult Scler 17:297–302CrossRefPubMedGoogle Scholar
  78. 78.
    Mader S, Gredler V, Schanda K et al (2011) Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders. J Neuroinflamm 8:184CrossRefGoogle Scholar
  79. 79.
    Huppke P, Rostasy K, Karenfort M et al (2013) Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler 19:941–946CrossRefPubMedGoogle Scholar
  80. 80.
    Hacohen Y, Absoud M, Woodhall M et al (2014) Autoantibody biomarkers in childhood-acquired demyelinating syndromes: results from a national surveillance cohort. J Neurol Neurosurg Psychiatry 85:456–461CrossRefPubMedGoogle Scholar
  81. 81.
    Lekoubou A, Viaccoz A, Didelot A et al (2012) Anti-N-methyl-d-aspartate receptor encephalitis with acute disseminated encephalomyelitis-like MRI features. Eur J Neurol 19:16–17CrossRefGoogle Scholar
  82. 82.
    Titulaer MJ, Höftberger R, Iizuka T et al (2014) Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 75:411–428PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of NeurologyMassachusetts General HospitalBostonUSA
  2. 2.Academic Medical Center - University of AmsterdamAmsterdamThe Netherlands
  3. 3.Harvard Medical SchoolBostonUSA

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