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Differential diagnosis of acute central nervous system demyelination in children

Timothy E Lotze, MD
Section Editors
Marc C Patterson, MD, FRACP
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD


Differential diagnostic considerations for acute central nervous system demyelination in children include acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), optic neuritis, transverse myelitis, neuromyelitis optica (Devic disease), and various infectious, metabolic, and rheumatologic conditions (table 1). Most of these conditions are thought to be caused by immune system dysregulation triggered by an infectious agent in a genetically susceptible host.

With the possible exception of the NMO-IgG autoantibody found in neuromyelitis optica, there are no disease-specific biomarkers for these conditions, making it difficult to distinguish among them at the time of the initial presentation. However, certain clinical features, laboratory results, and imaging findings can usually lead to the correct diagnosis. Multiple sclerosis is to a large extent still a diagnosis of exclusion, and therefore requires intense investigation for other conditions that might present in a similar manner.


Acute disseminated encephalomyelitis (ADEM) is characterized by acute or subacute onset of multifocal neurologic deficits with encephalopathy, often following a viral illness or vaccination. Additional typical signs associated with ADEM are headache, fever, or meningismus. Magnetic resonance imaging (MRI) demonstrates widespread asymmetric white and gray matter abnormalities (table 2). (See "Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis" and "Acute disseminated encephalomyelitis in children: Treatment and prognosis".)

In its classic form, ADEM is a monophasic disease, although the clinical features can fluctuate in severity and evolve in the first three months following disease onset [1]. However, relapsing ADEM (ie, multiphasic ADEM) has been reported in a minority. Multiphasic ADEM is defined as two episodes consistent with ADEM separated by three months, irrespective of glucocorticoid use, but not followed by any further events. The second ADEM event can involve either new or a re-emergence of prior neurologic symptoms, signs and MRI findings. Relapses beyond a second event are not consistent with ADEM according to current diagnostic criteria, but rather indicate a chronic disorder such as multiple sclerosis or neuromyelitis optica [1].

Acute hemorrhagic leukoencephalitis — Acute hemorrhagic leukoencephalitis is a rare entity that represents a more severe and fulminant form of ADEM and is associated with diffuse central nervous system hemorrhage. (See "Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis", section on 'Acute hemorrhagic leukoencephalitis'.)

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Literature review current through: Oct 2017. | This topic last updated: Dec 15, 2016.
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  1. 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.
  2. Stonehouse M, Gupte G, Wassmer E, Whitehouse WP. Acute disseminated encephalomyelitis: recognition in the hands of general paediatricians. Arch Dis Child 2003; 88:122.
  3. Oishi M, Mochizuki Y. Multiple sclerosis presenting as acute disseminated encephalomyelitis. J Neurol Sci 1998; 160:100.
  4. Menor F. [Demyelinating diseases in childhood: diagnostic contribution of magnetic resonance]. Rev Neurol 1997; 25:966.
  5. Kesselring J, Miller DH, Robb SA, et al. Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 1990; 113 ( Pt 2):291.
  6. Alper G, Heyman R, Wang L. Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol 2009; 51:480.
  7. 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.
  8. Callen DJ, Shroff MM, Branson HM, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology 2009; 72:968.
  9. Ketelslegers IA, Neuteboom RF, Boon M, et al. A comparison of MRI criteria for diagnosing pediatric ADEM and MS. Neurology 2010; 74:1412.
  10. Wolf VL, Lupo PJ, Lotze TE. Pediatric acute transverse myelitis overview and differential diagnosis. J Child Neurol 2012; 27:1426.
  11. Pidcock FS, Krishnan C, Crawford TO, et al. Acute transverse myelitis in childhood: center-based analysis of 47 cases. Neurology 2007; 68:1474.
  12. Frohman EM, Wingerchuk DM. Clinical practice. Transverse myelitis. N Engl J Med 2010; 363:564.
  13. O'Mahony J, Bar-Or A, Arnold DL, et al. Masquerades of acquired demyelination in children: experiences of a national demyelinating disease program. J Child Neurol 2013; 28:184.
  14. Hahn JS, Pohl D, Rensel M, et al. Differential diagnosis and evaluation in pediatric multiple sclerosis. Neurology 2007; 68:S13.
  15. Dagher AP, Smirniotopoulos J. Tumefactive demyelinating lesions. Neuroradiology 1996; 38:560.
  16. Bassuk AG, Keating GF, Stumpf DA, et al. Systemic lymphoma mimicking acute disseminated encephalomyelitis. Pediatr Neurol 2004; 30:129.
  17. Senatus PB, McClelland S 3rd, Tanji K, et al. The transformation of pediatric gliomatosis cerebri to cerebellar glioblastoma multiforme presenting as supra- and infratentorial acute disseminated encephalomyelitis. Case report. J Neurosurg 2005; 102:72.