Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis
- Timothy E Lotze, MD
Timothy E Lotze, MD
- Associate Professor of Pediatrics and Neurology
- Baylor College of Medicine
- Donald J Chadwick, MD
Donald J Chadwick, MD
- Adjunct Instructor
- Minneapolis Clinic of Neurology
Acute disseminated encephalomyelitis (ADEM), also known as postinfectious encephalomyelitis, is a demyelinating disease of the central nervous system that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy.
ADEM must be distinguished from other central inflammatory demyelinating conditions of childhood, including multiple sclerosis and clinically isolated syndromes that include optic neuritis, transverse myelitis, and neuromyelitis optica (Devic's disease). Most of these conditions are thought to be caused by immune system dysregulation triggered by an infectious or other environmental agent in a genetically susceptible host.
This topic will review the epidemiology, pathogenesis, clinical features, and diagnosis of ADEM in children. Treatment and prognosis of ADEM in children are discussed separately. (See "Acute disseminated encephalomyelitis in children: Treatment and prognosis".)
ADEM is an uncommon illness; the estimated incidence in California and Japan is 0.4/100,000 children per year [1,2], and in Canada is 0.2/100,000 per year . Approximately three to six cases are seen each year at regional medical centers in the United States, United Kingdom, and Australia [4-6]. There is no specific ethnic distribution . Several studies indicate a slight male predominance .
Postinfectious — ADEM is often preceded by a viral or bacterial infection, usually in the form of a nonspecific upper respiratory infection. In three series, an antecedent infection could be identified in 72 to 77 percent of patients [4,5,8]. A seasonal distribution also has been observed, with most cases presenting in the winter and spring [4,6]. In general, patients will present within one month of their illness.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J 2004; 23:756.
- Yamaguchi Y, Torisu H, Kira R, et al. A nationwide survey of pediatric acquired demyelinating syndromes in Japan. Neurology 2016; 87:2006.
- Banwell B, Kennedy J, Sadovnick D, et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology 2009; 72:232.
- Dale RC, de Sousa C, Chong WK, et al. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 2000; 123 Pt 12:2407.
- Hynson JL, Kornberg AJ, Coleman LT, et al. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 2001; 56:1308.
- Murthy SN, Faden HS, Cohen ME, Bakshi R. Acute disseminated encephalomyelitis in children. Pediatrics 2002; 110:e21.
- Tenembaum S, Chitnis T, Ness J, et al. Acute disseminated encephalomyelitis. Neurology 2007; 68:S23.
- Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology 2002; 59:1224.
- Pohl-Koppe A, Burchett SK, Thiele EA, Hafler DA. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. J Neuroimmunol 1998; 91:19.
- Stüve O, Zamvil SS. Pathogenesis, diagnosis, and treatment of acute disseminated encephalomyelitis. Curr Opin Neurol 1999; 12:395.
- Caldemeyer KS, Smith RR, Harris TM, Edwards MK. MRI in acute disseminated encephalomyelitis. Neuroradiology 1994; 36:216.
- David P, Baleriaux D, Bank WO, et al. MRI of acute disseminated encephalomyelitis after coxsackie B infection. J Neuroradiol 1993; 20:258.
- Kim SC, Jang HJ, Han DJ. Acute disseminated encephalomyelitis after renal transplantation in patients with positive Epstein-Barr virus antibody. Transplant Proc 1998; 30:3139.
- Shoji H, Kusuhara T, Honda Y, et al. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings. Neuroradiology 1992; 34:340.
- Apak RA, Köse G, Anlar B, et al. Acute disseminated encephalomyelitis in childhood: report of 10 cases. J Child Neurol 1999; 14:198.
- Huber S, Kappos L, Fuhr P, et al. Combined acute disseminated encephalomyelitis and acute motor axonal neuropathy after vaccination for hepatitis A and infection with Campylobacter jejuni. J Neurol 1999; 246:1204.
- Murthy JM. MRI in acute disseminated encephalomyelitis following Semple antirabies vaccine. Neuroradiology 1998; 40:420.
- Stonehouse M, Gupte G, Wassmer E, Whitehouse WP. Acute disseminated encephalomyelitis: recognition in the hands of general paediatricians. Arch Dis Child 2003; 88:122.
- Fenichel GM. Neurological complications of immunization. Ann Neurol 1982; 12:119.
- Menge T, Hemmer B, Nessler S, et al. Acute disseminated encephalomyelitis: an update. Arch Neurol 2005; 62:1673.
- Bray PF, Luka J, Bray PF, et al. Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein. Neurology 1992; 42:1798.
- Becher B, Bechmann I, Greter M. Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. J Mol Med (Berl) 2006; 84:532.
- Greter M, Heppner FL, Lemos MP, et al. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 2005; 11:328.
- Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol 2005; 23:683.
- Pitt D, Werner P, Raine CS. Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 2000; 6:67.
- Whitaker JN, Kirk KA, Herman PK, et al. An immunochemical comparison of human myelin basic protein and its modified, citrullinated form, C8. J Neuroimmunol 1992; 36:135.
- Bauer J, Stadelmann C, Bancher C, et al. Apoptosis of T lymphocytes in acute disseminated encephalomyelitis. Acta Neuropathol 1999; 97:543.
- Gold R, Hartung HP, Toyka KV. Animal models for autoimmune demyelinating disorders of the nervous system. Mol Med Today 2000; 6:88.
- Brass SD, Caramanos Z, Santos C, et al. Multiple sclerosis vs acute disseminated encephalomyelitis in childhood. Pediatr Neurol 2003; 29:227.
- Fridinger SE, Alper G. Defining encephalopathy in acute disseminated encephalomyelitis. J Child Neurol 2014; 29:751.
- Davis LE, Booss J. Acute disseminated encephalomyelitis in children: a changing picture. Pediatr Infect Dis J 2003; 22:829.
- Seales D, Greer M. Acute hemorrhagic leukoencephalitis. A successful recovery. Arch Neurol 1991; 48:1086.
- Klein CJ, Wijdicks EF, Earnest F 4th. Full recovery after acute hemorrhagic leukoencephalitis (Hurst's disease). J Neurol 2000; 247:977.
- Rosman NP, Gottlieb SM, Bernstein CA. Acute hemorrhagic leukoencephalitis: recovery and reversal of magnetic resonance imaging findings in a child. J Child Neurol 1997; 12:448.
- Lieberman AP, Grossman RI, Lavi E. Case of the month: April 1997--a 32 year old man with mental status changes and a severe occipital headache. Brain Pathol 1998; 8:229.
- Kuperan S, Ostrow P, Landi MK, Bakshi R. Acute hemorrhagic leukoencephalitis vs ADEM: FLAIR MRI and neuropathology findings. Neurology 2003; 60:721.
- Mader I, Wolff M, Niemann G, Küker W. Acute haemorrhagic encephalomyelitis (AHEM): MRI findings. Neuropediatrics 2004; 35:143.
- Alper G. Acute disseminated encephalomyelitis. J Child Neurol 2012; 27:1408.
- Callen DJ, Shroff MM, Branson HM, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology 2009; 72:968.
- Verhey LH, Branson HM, Shroff MM, et al. MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. Lancet Neurol 2011; 10:1065.
- Baum PA, Barkovich AJ, Koch TK, Berg BO. Deep gray matter involvement in children with acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 1994; 15:1275.
- Abu Libdeh A, Goodkin HP, Ramirez-Montealegre D, Brenton JN. Acute Disseminated Encephalomyelitis: A Gray Distinction. Pediatr Neurol 2017; 68:64.
- Krupp LB, Banwell B, Tenembaum S, International Pediatric MS Study Group. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68:S7.
- Krupp LB, Tardieu M, Amato MP, et al. 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 2013; 19:1261.
- Priming and activation phase
- Recruitment and effector phase
- CLINICAL FEATURES
- Clinical course
- Acute hemorrhagic leukoencephalitis
- Lumbar puncture
- Laboratory studies
- Diagnostic criteria
- - Monophasic ADEM
- - Multiphasic ADEM
- Differential diagnosis
- SUMMARY AND RECOMMENDATIONS