Neuropsychology Review

, Volume 27, Issue 2, pp 124–133 | Cite as

Long-Term Neuropsychological Outcomes of Childhood Onset Acute Disseminated Encephalomyelitis (ADEM): a Meta-Analysis

  • Karen L. O. Burton
  • Tracey A. WilliamsEmail author
  • Sarah E. Catchpoole
  • Ruth K. Brunsdon


The long-term neurocognitive prognosis of childhood onset acute disseminated encephalomyelitis (ADEM) is unclear. This review and quantitative synthesis of the available literature examined whether there are long-term impacts of childhood ADEM on neurocognitive functioning. A search of online databases (MEDLINE, EMBASE, EBSCO CINAHL, PsycINFO and the Cochrane Database of Systematic Reviews) from their inception to October 2015 and reference lists identified 13 papers eligible for inclusion in the systematic review; seven of these were eligible for inclusion in meta-analyses. The systematic review indicated that, at a group level there is a positive long-term neuropsychological outcome from childhood onset ADEM. However, despite the apparent absence of long-term negative impacts of ADEM at a group level, at an individual level impairments in the areas of IQ, attention, executive functioning, processing speed, learning and memory, visuospatial skills and internalising symptoms were found in up to 43% of patients when aggregated across the studies. No significant negative effect of ADEM for any of the neuropsychological domains examined was found in meta-analyses. However, the effects for Processing Speed (r mean = −0.296 (CI 95% = −0.605-0.013)) and Internalising symptoms (r mean = 0.242 (CI 95% = −0.014-0.564)) approached significance (p = 0.06), suggesting a trend towards ADEM leading to long-term reduced processing speed and elevated internalising symptoms. Together, our findings suggest that despite a generally positive neurocognitive outcome post childhood ADEM there are a subset of individuals who can suffer from ongoing specific cognitive impairments. Clinical implications and research priorities are discussed.


Acute disseminated encephalomyelitis ADEM Paediatric Neuropsychology Meta-analysis 

Supplementary material

11065_2017_9343_MOESM1_ESM.docx (48 kb)
ESM 1 (DOCX 48 kb)


  1. Achenbach, T. M., & Edelbrock, C. S. (1986). Child behaviour checklist and youth self-report. Burlington: University of Vermont, Department of Psychiatry.Google Scholar
  2. Anderson, V., Lajoie, G., & Bell, R. (1995). Neuropsychological assessment of the school-aged child. Melbourne: University of Melbourne.Google Scholar
  3. Anderson, P., Anderson, V., Northam, E., & Taylor, H. G. (2000). Standardization of the contingency naming test (CNT) for school-aged children: A measure of reactive flexibility. Clinical Neuropsychological Assessment, 1, 247–273.Google Scholar
  4. Anderson, P., Anderson, V., & Garth, J. (2001). Assessment and development of organizational ability: The Rey complex figure organizational strategy score (RCF-OSS). The Clinical Neuropsychologist, 15, 81–94.CrossRefPubMedGoogle Scholar
  5. Anderson, V., Catroppa, C., Morse, S., Haritou, F., & Rosenfeld, J. (2005a). Attentional processing skills following traumatic brain injury in early childhood. Brain Injury, 19(9), 699–710. doi: 10.1080/02699050400025281.CrossRefPubMedGoogle Scholar
  6. Anderson, V., Catroppa, C., Morse, S., Haritou, F., & Rosenfeld, J. (2005b). Functional plasticity or vulnerability after early brain injury? Pediatrics, 116(6), 1374–1382. doi: 10.1542/peds.2004-1728.CrossRefPubMedGoogle Scholar
  7. Army Individual Battery Test. (1944). Manual of directions and scoring. Washington DC: War Department, Adjunct General's Office.Google Scholar
  8. Biostat Inc. (2014). Comprehensive meta-analysis (CMA) (Version 3.3.070). Englewood: Biostat Retrieved from Scholar
  9. Bisiacchi, P. S., Cendron, M., Gugliotta, M., Tressoldi, P., & Vio, C. (2005). Batteria di Valutazione Neuropsicologica per I'Eta Evolutiva. Trento: Erickson.Google Scholar
  10. Brunet, O., & Lezine, I. (1967). Scala di Sviluppo Psicomotorio della Prima Infanzia. Florence: Organizzazioni Scientifiche.Google Scholar
  11. Cohen, M. (1997). Children's memory scale (CMS). San Antonio: The Psychological Corporation.Google Scholar
  12. Conners, K. C. (2000). Conners' continuous performance test II (CPT II). Toronto: Multi-Health Systems Inc..Google Scholar
  13. Dale, R. C., de Sousa, C., Chong, W. K., Cox, T. C., Harding, B., & Neville, B. G. (2000). Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain, 123, 2407–2422.CrossRefPubMedGoogle Scholar
  14. Deery, B., Anderson, V., Jacobs, R., Neale, J., & Kornberg, A. (2010). Childhood MS and ADEM: Investigation and comparison of neurocognitive features in children. Developmental Neuropsychology, 35(5), 506–521.CrossRefPubMedGoogle Scholar
  15. Delis, D. C., Kaplan, E., & Kramer, J. H. (2001). Delis-Kaplan executive function system (D-KEFS). San Antonio: The Psychological Corporation.Google Scholar
  16. Duval, S., & Tweedie, R. (2000a). A nonparametric 'trim and fill' method of accounting for publication bias in meta-analysis. Journal of the American Statistical Association, 95, 89–98.Google Scholar
  17. Duval, S., & Tweedie, R. (2000b). Trim and fill: A simple funnel-plot based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 56, 455–463.CrossRefPubMedGoogle Scholar
  18. Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal, 315, 629–634.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gaddes, W. H., & Crockett, D. J. (1975). The Spreen Benton aphasia tests: Normative data as a measure of normal language development. Brain and Language, 2, 257–279.CrossRefPubMedGoogle Scholar
  20. Grant, D. A., & Berg, E. A. (1993). The Wisconsin card sorting test. San Antonio: The Psychological Corporation.Google Scholar
  21. Hahn, C. D., Miles, B. S., MacGregor, D. L., Blaser, S. I., Banwell, B. L., & Hetherington, C. R. (2003). Neurocognitive outcome after acute disseminated encephalomyelitis. Pediatric Neurology, 29(2), 117–123.CrossRefPubMedGoogle Scholar
  22. Heaton, R. K., Chelune, G. J., & Talley, J. L. (1993). Wisconsin card sorting test manual. Odessa: Psychological Assessment Resources.Google Scholar
  23. Holland, B. A., Haas, D. K., Norman, D., Brant-Zawadzki, M., & Newton, T. H. (1986). MRI of normal brain maturation. American Journal of Neuroradiology, 7(2), 201–208.PubMedGoogle Scholar
  24. Hynson, J. L., Kornberg, A. J., Coleman, L. T., Shield, L., Harvey, A. S., & Kean, M. J. (2001). Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology, 56(10), 1308–1312.CrossRefPubMedGoogle Scholar
  25. Jacobs, R. K., Anderson, V. A., Neale, J. L., Shield, L. K., & Kornberg, A. J. (2004). Neuropsychological outcome after acute disseminated encephalomyelitis: Impact of age at illness onset. Pediatric Neurology, 31(3), 191–197.CrossRefPubMedGoogle Scholar
  26. Jastak, S., & Wilkinson, G. (1994). The wide range achievement test 3. Wilmington: Wide Range Incorporated, Jastak Associates.Google Scholar
  27. Jayakrishnan, M. P., & Krishnakumar, P. (2010). Clinical profile of acute disseminated encephalomyelitis in children. Journal of Pediatric Neurosciences, 5(2), 111–114.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Jonsson, C. A., Catroppa, C., Godfrey, C., Smedler, A.-C., & Anderson, V. (2013). Cognitive recovery and development after traumatic brain injury in childhood: A person-oriented, longitudinal study. Journal of Neurotrauma, 30(2), 76–83. doi: 10.1089/neu.2012.2592.CrossRefPubMedGoogle Scholar
  29. Klinberg, T., Vaidya, C. J., Gabrieli, J. D. E., Moseley, M. E., & Hedehus, M. (1999). Myelination and oraganization of the frontal white matter in children: A diffusion tensor MRI study. Neuroreport, 10(13), 2817–2821.CrossRefGoogle Scholar
  30. Kothare, S., Adams, R., Valencia, I., Faerber, E., & Grant, M. (2007). Improved sleep and neurocognitive functions in a child with thalamic lesions on sodium oxybate. Neurology, 68(14), 1157–1158.CrossRefPubMedGoogle Scholar
  31. Kuni, B. J., Banwell, B. L., & Till, C. (2012). Cognitive and behavioral outcomes in individuals with a history of acute disseminated encephalomyelitis (ADEM). Developmental Neuropsychology, 37(8), 682–696.CrossRefPubMedGoogle Scholar
  32. Lezak, M. D., Howieson, D. B., & Loring, D. W. (Eds.). (2004). Neuropsychological assessment (4th ed.). New York: Oxford University Press.Google Scholar
  33. Light, R. J., & Pillemer, D. B. (1984). Summing up: the science of reviewing research. Cambridge, MA: Harvard University Press.Google Scholar
  34. Light, R. J., Singer, J. D., & Willett, J. B. (1994). The visual presentation and interpretation of meta-analyses. In M. Coper & L. V. Hedges (Eds.), The handbook of research synthesis. New York: Russell Sage Foundation.Google Scholar
  35. McKay, K. E., Halperin, J. M., Schwartz, S. T., & Sharma, V. (1994). Developmental analysis of three aspects of information processing: Sustained attention, selective attention, and response organization. Developmental Neuropsychology, 10(2), 121–132. doi: 10.1080/87565649409540572.CrossRefGoogle Scholar
  36. Menge, T., Kieseier, B. C., Nessler, S., Hemmer, B., Hartung, H.-P., & Stuve, O. (2007). Acute disseminated encephalomyelitis: An acute hit against the brain. Current Opinions in Neuology, 20, 247–254.CrossRefGoogle Scholar
  37. Muir, K. E., McKenney, K. S., Connolly, M. B., & Evelyn Stewart, S. (2013). A case report of obsessive-compulsive disorder following acute disseminated encephalomyelitis. Pediatrics, 132(3), e771–e774.CrossRefPubMedGoogle Scholar
  38. Nagy, Z., Westerberg, H., & Klingberg, T. (2004). Maturation of white matter is associated with the development of cognitive functions during childhood. Journal of Cognitive Neuroscience, 16(7), 1227–1233. doi: 10.1162/0898929041920441.CrossRefPubMedGoogle Scholar
  39. Noorbakhsh, F., Johnson, R. T., Emery, D., & Powell, C. (2008). Acute disseminated encephalomyelitis: Clinical and pathogenesis features. Neurologic Clinics, 26, 759–780.CrossRefPubMedGoogle Scholar
  40. Parrish, J. B., Weinstock-Guttman, B., Smerbeck, A., Benedict, R. H., & Yeh, E. A. (2013). Fatigue and depression in children with demyelinating disorders. Journal of Child Neurology, 28(6), 713–718.CrossRefPubMedGoogle Scholar
  41. Pavone, P., Pettoello-Mantovano, M., Le Pira, A., Giardino, I., Pulvirenti, A., Giugno, R., et al. (2010). Acute disseminated encephalomyelitis: A long-term prospective study and meta-analysis. Neuropediatrics, 41(6), 246–255.CrossRefPubMedGoogle Scholar
  42. Perniola, T., Margari, L., Buttiglione, M., Andreula, C., Simone, I. L., & Santostasi, R. (1993). A case of landau-Kleffner syndrome secondary to inflammatory demyelinating disease. Epilepsia, 34(3), 551–556.CrossRefPubMedGoogle Scholar
  43. Pillai, S. C., Hacohen, Y., Tantsis, E., Prelog, K., Merheb, V., Kesson, A., et al. (2015). Infectious and autoantibody-associated encephalitis: Clinical features and long-term outcome. Pediatrics, 135(4), e974–e984.CrossRefPubMedGoogle Scholar
  44. Reitan, R. M. (1986). Trail making test: Manual for administration and scoring. Tucson: Reitan Neuropsychology Laboratory.Google Scholar
  45. Rey, A. (1964). L'edamen clinique en psychologie. Paris: Press Universitaire de France.Google Scholar
  46. Reynolds, C. R., & Kamphaus, R. W. (1992). Manual for the behavior assessment system for children. Minnesota: American Guidance Services.Google Scholar
  47. Reynolds, C. R., & Kamphaus, R. W. (2004). Behavior assessment system for children (BASC-2) (2nd ed.). Bloomington: Pearson.Google Scholar
  48. Reynolds, C. R., & Voress, J. K. (2007). Test of memory and learning (TOMAL-2) (2nd ed.). Austin: Pro-Ed.Google Scholar
  49. Rostasy, K., Nagl, A., Lutjen, S., Roll, K., Zotter, S., Blaschek, A., et al. (2009). Clinical outcome of children presenting with a severe manifestation of acute disseminated encephalomyelitis. Neuropediatrics, 40(5), 211–217.CrossRefPubMedGoogle Scholar
  50. Sannio Facello, G., Vio, C., & Cianchetti, C. (2006). TOL Torre di Londra, test ti valutazione delle fuzioni esecutive (pianificazione e problem solving). Trento: Erickson.Google Scholar
  51. Strauss, E., Sherman, E. M. S., & Spreen, O. (Eds.). (2006). A compendium of neuropsychological tests: Administration, norms, and commentary. New York: Oxford University Press.Google Scholar
  52. Suppiej, A., Cainelli, E., Casara, G., Cappellari, A., Nosadini, M., & Sartori, S. (2014). Long-term neurocognitive outcome and quality of life in pediatric acute disseminated encephalomyelitis. Pediatric Neurology, 50(4), 363–367.CrossRefPubMedGoogle Scholar
  53. Taylor, H. G., & Alden, J. (1997). Age-related differences in outcomes following childhood brain insults: An introduction and overview. Journal of International Neuropsychological Society, 3(6), 555–567.Google Scholar
  54. Taylor, H. G., Albo, V., Phebus, C., Sachs, B., & Bierl, P. (1987). Postiradiation treatment outcomes for children with acute lymphoblastic leukemia: Clarification of risks. Journal of Pediatric Psychology, 12, 395–411.CrossRefPubMedGoogle Scholar
  55. Tenembaum, S. N. (2008). Disseminated encephalomyelitis in children. Clinical Neurol Neurosurg, 1119, 928–938.CrossRefGoogle Scholar
  56. Tenembaum, S., Chamoles, N., & Fejerman, N. (2002). Acute disseminated encephalomyelitis: A long-term follow-up study of 84 pediatric patients. Neurology, 59, 1224–1231.CrossRefPubMedGoogle Scholar
  57. Wechsler, D. (1949). Wechsler intelligence scale for children. San Antonio: Psychological Corporation.Google Scholar
  58. Wechsler, D. (1955). Wechsler Adult Intelligence Scale. Oxford: Psychological Corporation.Google Scholar
  59. Wechsler, D. (1989). Wechsler preschool and primary scale of intelligence - revised. San Antonio: Psychological Corporation, Harcourt, Barce, Jovanovich.Google Scholar
  60. Wechsler, D. (1991). Wechsler intelligence scale for children - Third Edition (WISC-III).Google Scholar
  61. Wechsler, D. (1992). Wechsler individual achievement test (WIAT). San Antonio: The Psychological Corporation.Google Scholar
  62. Wechsler, D. (1999). Wechsler abbreviated scale of intelligence (WASI). San Antonio: The Psychological Corporation.Google Scholar
  63. Woodcock, R. W., McGrew, K. S., & Mather, N. (2007). Woodcock Johnson III (WJ-III) tests of achivement, form B, with normative update. Chicago: Riverside Publishing.Google Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Karen L. O. Burton
    • 1
  • Tracey A. Williams
    • 1
    Email author
  • Sarah E. Catchpoole
    • 2
  • Ruth K. Brunsdon
    • 1
  1. 1.Kids RehabThe Children’s Hospital at WestmeadWestmeadAustralia
  2. 2.Sydney Medical SchoolUniversity of SydneySydneyAustralia

Personalised recommendations