Acute disseminated encephalomyelitis in adults
- Amy T Waldman, MD
Amy T Waldman, MD
- Assistant Professor of Child Neurology
- Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
Acute disseminated encephalomyelitis (ADEM), also known as postinfectious encephalomyelitis, is an autoimmune demyelinating disease of the central nervous system. Commonly triggered by viral infections and immunizations, ADEM is caused by an inflammatory reaction in the brain and spinal cord. Its onset is acute and often rapidly progressive. ADEM is typically monophasic, but some patients may either have recurrences, or are at risk for the development of multiple sclerosis.
This topic will review the pathogenesis, pathology, epidemiology, clinical features, diagnosis, and treatment of acute disseminated encephalomyelitis in adults. Clinical aspects of ADEM in children are discussed separately. (See "Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis" and "Acute disseminated encephalomyelitis in children: Treatment and prognosis".)
The pathogenesis of ADEM is reviewed here briefly and discussed in greater detail separately. (See "Acute disseminated encephalomyelitis in children: Pathogenesis, clinical features, and diagnosis", section on 'Pathogenesis'.)
Although the pathogenesis is incompletely understood, ADEM appears to be an autoimmune disorder of the central nervous system that is triggered by an environmental stimulus in genetically susceptible individuals. One proposed mechanism is that myelin autoantigens, such as myelin basic protein, proteolipid protein, and myelin oligodendrocyte protein, share antigenic determinants with those of an infecting pathogen. Antiviral antibodies or a cell-mediated response to the pathogen cross react with the myelin autoantigens, resulting in ADEM.
Alternatively, ADEM may be due to increased vascular permeability and congestion in the central nervous system, perhaps triggered by circulating immune complexes or other humoral factors that develop after the appearance of a foreign antigen introduced by infection or vaccination [1-4]. This process then leads to infiltration of the vessel walls by mononuclear cells, followed by perivenous edema and occasionally hemorrhages. Within days, microglia, lymphocytes, and phagocytes appear, ultimately causing demyelination and possible gliosis and necrosis. The extent of demyelination and subsequent glial and neuronal changes account for the variation in clinical features and disease prognosis.
- Poser CM. Disseminad vasculomyelinopathy. A review of the clinical and pathologic reactions of the nervous system in hyperergic diseases. Acta Neurol Scand 1969; :Suppl 37:3.
- Reik L Jr. Disseminated vasculomyelinopathy: an immune complex disease. Ann Neurol 1980; 7:291.
- Poser CM. Disseminated vasculomyelinopathy. Ann Neurol 1980; 8:550.
- Rudick RA, Eskin TA. Enhanced vascular permeability in acute disseminated vasculomyelinopathy. Ann Neurol 1981; 9:621.
- van der Knaap MS, Valk J. Acute disseminated encephalomyelitis and acute hemorrhagic encephalomyelitis. In: Magnetic Resonance of Myelination and Myelin Disorders, 3rd edition, Springer, New York 2005. p.604.
- Hawkins CP, Mackenzie F, Tofts P, et al. Patterns of blood-brain barrier breakdown in inflammatory demyelination. Brain 1991; 114 ( Pt 2):801.
- Hart MN, Earle KM. Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases. J Neurol Neurosurg Psychiatry 1975; 38:585.
- Kepes JJ. Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. Ann Neurol 1993; 33:18.
- Mader I, Stock KW, Ettlin T, Probst A. Acute disseminated encephalomyelitis: MR and CT features. AJNR Am J Neuroradiol 1996; 17:104.
- Cohen O, Steiner-Birmanns B, Biran I, et al. Recurrence of acute disseminated encephalomyelitis at the previously affected brain site. Arch Neurol 2001; 58:797.
- VAN BOGAERT L. Post-infectious encephalomyelitis and multiple sclerosis; the significance of perivenous encephalomyelitis. J Neuropathol Exp Neurol 1950; 9:219.
- Young NP, Weinshenker BG, Parisi JE, et al. Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain 2010; 133:333.
- Ghosh N, DeLuca GC, Esiri MM. Evidence of axonal damage in human acute demyelinating diseases. J Neurol Sci 2004; 222:29.
- Garg RK. Acute disseminated encephalomyelitis. Postgrad Med J 2003; 79:11.
- Ketelslegers IA, Visser IE, Neuteboom RF, et al. Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children. Mult Scler 2011; 17:441.
- Noorbakhsh F, Johnson RT, Emery D, Power C. Acute disseminated encephalomyelitis: clinical and pathogenesis features. Neurol Clin 2008; 26:759.
- Schwarz S, Mohr A, Knauth M, et al. Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology 2001; 56:1313.
- de Seze J, Debouverie M, Zephir H, et al. Acute fulminant demyelinating disease: a descriptive study of 60 patients. Arch Neurol 2007; 64:1426.
- Sonneville R, Demeret S, Klein I, et al. Acute disseminated encephalomyelitisin the intensive care unit:clinical features and outcome of 20 adults. Intensive Care Med 2008; 34:528.
- Höllinger P, Sturzenegger M, Mathis J, et al. Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF, EEG, and MRI findings. J Neurol 2002; 249:320.
- Kaji M, Kusuhara T, Ayabe M, et al. Survey of herpes simplex virus infections of the central nervous system, including acute disseminated encephalomyelitis, in the Kyushu and Okinawa regions of Japan. Mult Scler 1996; 2:83.
- Denes E, Magy L, Pradeau K, et al. Successful treatment of human herpesvirus 6 encephalomyelitis in immunocompetent patient. Emerg Infect Dis 2004; 10:729.
- Silver B, McAvoy K, Mikesell S, Smith TW. Fulminating encephalopathy with perivenular demyelination and vacuolar myelopathy as the initial presentation of human immunodeficiency virus infection. Arch Neurol 1997; 54:647.
- Tsiodras S, Kelesidis T, Kelesidis I, et al. Mycoplasma pneumoniae-associated myelitis: a comprehensive review. Eur J Neurol 2006; 13:112.
- Marchioni E, Ravaglia S, Piccolo G, et al. Postinfectious inflammatory disorders: subgroups based on prospective follow-up. Neurology 2005; 65:1057.
- APPELBAUM E, NELSON J. Neurological complications following antirabies vaccination. J Am Med Assoc 1953; 151:188.
- Feery BJ. Adverse reactions after smallpox vaccination. Med J Aust 1977; 2:180.
- Fenichel GM. Neurological complications of immunization. Ann Neurol 1982; 12:119.
- Holt S, Hudgins D, Krishnan KR, Critchley EM. Diffuse myelitis associated with rubella vaccination. Br Med J 1976; 2:1037.
- Behan PO. Diffuse myelitis associated with rubella vaccination. Br Med J 1977; 1:166.
- Honkaniemi J, Dastidar P, Kähärä V, Haapasalo H. Delayed MR imaging changes in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 2001; 22:1117.
- Marchioni E, Ravaglia S, Montomoli C, et al. Postinfectious neurologic syndromes: a prospective cohort study. Neurology 2013; 80:882.
- Kuperan S, Ostrow P, Landi MK, Bakshi R. Acute hemorrhagic leukoencephalitis vs ADEM: FLAIR MRI and neuropathology findings. Neurology 2003; 60:721.
- Atlas SW, Grossman RI, Goldberg HI, et al. MR diagnosis of acute disseminated encephalomyelitis. J Comput Assist Tomogr 1986; 10:798.
- Singh S, Alexander M, Korah IP. Acute disseminated encephalomyelitis: MR imaging features. AJR Am J Roentgenol 1999; 173:1101.
- Marin SE, Callen DJ. The magnetic resonance imaging appearance of monophasic acute disseminated encephalomyelitis: an update post application of the 2007 consensus criteria. Neuroimaging Clin N Am 2013; 23:245.
- Balasubramanya KS, Kovoor JM, Jayakumar PN, et al. Diffusion-weighted imaging and proton MR spectroscopy in the characterization of acute disseminated encephalomyelitis. Neuroradiology 2007; 49:177.
- Lakhan SE. Teaching neuroimages: MRI time lag with acute disseminated encephalomyelitis. Neurology 2012; 78:e138.
- Khurana DS, Melvin JJ, Kothare SV, et al. Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis. Pediatrics 2005; 116:431.
- 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.
- Keegan M, Pineda AA, McClelland RL, et al. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002; 58:143.
- Marchioni E, Marinou-Aktipi K, Uggetti C, et al. Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis. J Neurol 2002; 249:100.
- Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 76:294.
- Lin CH, Jeng JS, Hsieh ST, et al. Acute disseminated encephalomyelitis: a follow-up study in Taiwan. J Neurol Neurosurg Psychiatry 2007; 78:162.
- Durston JH, Milnes JN. Relapsing encephalomyelitis. Brain 1970; 93:715.
- CLINICAL FEATURES
- Variant forms
- - Acute hemorrhagic encephalomyelitis
- - ADEM with peripheral nervous system involvement
- Lumbar puncture
- Other studies
- DIFFERENTIAL DIAGNOSIS
- Multiple sclerosis
- Infectious meningoencephalitis
- Progressive multifocal leukoencephalopathy
- Behçet's syndrome
- Intravenous immune globulin
- Plasma exchange
- SUMMARY AND RECOMMENDATIONS