• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
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Acute Disseminated Encephalomyelitis

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Last updated: July 07, 2022
Years published: 2013, 2022


Acknowledgment

NORD gratefully acknowledges Christopher Rizkalli and Emma Kozuch, NORD Editorial Interns from the University of Notre Dame, and J. Nicholas Brenton, MD, Director, Pediatric MS & Related Disorders Clinic, Associate Professor of Pediatrics and Neurology, University of Virginia, for assistance in the preparation of this report.


Disease Overview

Summary

Acute disseminated encephalomyelitis (ADEM) is a neurological, immune-mediated disorder in which widespread inflammation of the central nervous system (brain and spinal cord) damages tissue known as white matter. White matter is composed of nerve fibers that are covered by a collection of fats and proteins known as myelin. Myelin, also called the myelin sheath, protects the nerve fibers, acts as an insulator and increases the speed of transmission of nerve signals. Damage to the myelin sheath (demyelination) affects the ability of the nerves to transmit information and can potentially cause a wide range of neurological symptoms.

The most common neurological symptoms of ADEM include arm/leg weakness, seizures, numbness or tingling, changes in mental status and vision loss; however, the specific symptoms and severity can vary between individuals. Onset can be at any age, but children are more likely to be affected than adults. Long-term outcomes for patients are generally favorable. The exact cause of ADEM is unknown, but it is thought to be associated with an autoimmune response that is triggered by an infection or, in rare instances, certain vaccinations.

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Synonyms

  • ADEM
  • ADE
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Subdivisions

  • acute hemorrhagic leukoencephalitis
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Signs & Symptoms

Symptoms of ADEM can present within days to weeks following an infection. In a subset of patients, there is no identifiable infectious “trigger” for ADEM. Most commonly, ADEM occurs only once in a particular individual, meaning the disease is most often considered a monophasic disorder; however, a small percentage of patients may exhibit future attacks of ADEM (termed multiphasic ADEM).

The extent and progression of ADEM symptoms vary between affected individuals and may depend on the location of the brain lesions and the age of onset. Some individuals may have a mild, limited form of the disorder, while others may develop more severe symptoms. In the most severe cases, life-threatening complications such as respiratory failure is possible.

Initial symptoms usually develop rapidly and are common to many different illnesses, such as the flu. These symptoms are considered nonspecific and include headache, fever, irritability, fatigue, lethargy and a general feeling of ill health (malaise). Nausea and vomiting may be present and lead to unintended weight loss. Confusion, stupor and delirium may also occur, and severely affected patients may fall into a coma.

Additional neurological symptoms include the inability to coordinate voluntary movements (ataxia), weakness of the arms and/or legs, slurred speech, cranial nerve dysfunction, numbness of the body and seizures. Seizures are more common in children than adults, typically occurring in children under five years of age. Inflammation of the optic nerve(s) (optic neuritis) may develop along with ADEM and result in vision loss.

Adults with ADEM may exhibit peripheral nerve damage (neuropathy). Individuals with neuropathy can experience weakness, pain, numbness or a burning or tingling sensation in the extremities and they typically have a worse prognosis. In some people, additional symptoms may develop including involuntary movements, amnesia, personality changes and depression. This appears to be a rare occurrence in children. Rarely, ataxia has been reported in patients who had ADEM following a Sars-Cov-2 infection. It is important to diagnose and treat ADEM associated with Sars-Cov-2 early to prevent poor outcomes.

Acute hemorrhagic leukoencephalitis (AHL) is thought to be a severe, hyperacute form of ADEM. This variant is associated with rapid onset of fever, headaches, vomiting, neck stiffness and seizures. It may involve the neurological signs and symptoms associated with ADEM. AHL is often associated with rapid deterioration and life-threatening complications such as swelling of the brain (brain edema). Despite the severe, rapid course of AHL, some individuals have had a favorable neurological outcome when treated quickly and aggressively.

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Causes

The exact cause of ADEM is not known but it may be associated with an atypical immune response following an infectious trigger. An initial illness or infection is observed in 70-80% of patients with ADEM. For instance, ADEM can develop following an upper respiratory tract viral infection. Other ADEM inducing infections include influenza, measles, mumps, rubella, varicella-zoster, Epstein Barr virus, cytomegalovirus and herpes simplex virus.

Less commonly, ADEM may develop following a vaccination, but this has become very rare and noted in <5% of all ADEM cases. These case reports do not necessarily indicate that ADEM is caused by vaccination.

Recent studies indicate that ADEM is also linked to the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG). MOG is a protein that is found in the CNS and is a component of the myelin sheath. Antibodies to the MOG protein, more commonly noted in children, have been linked to a variety of inflammatory demyelinating conditions including ADEM.

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Affected populations

ADEM can develop at any age but is much more frequent in younger children. Outcomes and severity of ADEM are typically worse in adults than in children. Males and females are affected, but males may be affected more often. In children, the mean age of onset is between 5-8 years old, but ADEM has been diagnosed in children as young as 7 months.

The incidence of ADEM in the general population is unknown, but the incidence of childhood ADEM is estimated to be 0.07 – 0.09 per 100,000. In the U.S., ADEM seems to peak in the winter and spring months and evidence also suggests that incidence increases with increasing distance from the equator.

ADEM is not an inherited disorder, but genetic factors may play a role in the risk to develop ADEM.

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Diagnosis

A diagnosis of ADEM is made based on the identification of characteristic symptoms, a detailed patient history, thorough clinical evaluation and a variety of specialized tests including imaging techniques such as magnetic resonance imaging (MRI). An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues and can demonstrate characteristic brain lesions in individuals with ADEM. Additional tests such as spinal fluid testing may be needed to exclude other conditions.

New diagnostic serum testing for the myelin oligodendrocyte glycoprotein antibody (MOG-Ab), a protein that makes up the myelin sheath in the CNS, is being increasingly utilized. This test is a cell-based assay that specifically tests for the presence of antibodies against the MOG protein which has been associated with a variety of CNS demyelinating disorders such as ADEM.

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Standard Therapies

Treatment

No standard therapy for ADEM has been established. Most therapies that have been used to treat ADEM have some effect of modifying the activity of the host immune system. Such therapies include corticosteroids, immunoglobulin (IVIg) therapy or plasmapheresis.

High doses of corticosteroids are the primary treatment for ADEM and are generally effective. Methylprednisolone and dexamethasone are the most prescribed corticosteroids. These medications typically reduce the severity of symptoms and hasten recovery in affected individuals but may cause significant side effects such as alterations in mood and behavior, irritated stomach lining and elevated blood pressure or blood sugar.

Intravenous immunoglobulin (IVIg) may be used to treat patients with ADEM who do not respond to or have an intolerance to corticosteroid therapy. IVIg is a concentrated solution of antibodies that have been extracted from the blood of healthy donors. IVIg is effective against autoimmune disorders because the extracted antibodies neutralize the effects of autoantibodies (antibodies that target healthy tissues).

Plasmapheresis has been used to treat patients with ADEM who do not respond to other forms of therapy. Plasmapheresis filters toxins and metabolic substances from the blood. The procedure works by separating blood cells from plasma. The patient’s plasma is then replaced with human plasma and the patient’s blood (blood cells and plasma) is transfused back into the body. The treatment typically requires hospitalization and is performed every other day for 10-14 days. Other possible second-line treatments include intravenous immunosuppressive medications such as rituximab or cyclophosphamide.

Rehabilitation therapy may be helpful for affected individuals that experience longer-term effects such as cognitive and speech impairments, epilepsy and visual and/or motor problems.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

JOURNAL ARTICLES
Almaghrabi N, Saab A. Adult onset acute disseminated encephalomyelitis: A case report. Radiol Case Rep. 2021;16(9):2469-2473. doi: 10.1016/j.radcr.2021.05.052
Ghosh R, Dubey S, Mandal A, Ray BK, Benito-León J. Complex movement disorders in SARS-CoV-2 infection induced acute disseminated encephalomyelitis. J Neuroimmunol. 2021;358:577655. doi: S0165- 5728(21)00182-X

Mahapure KS, Prabhune AS, Chouvhan AV. COVID-19-associated acute disseminated encephalomyelitis: A systematic review. Asian J Neurosurg. 2021;16(3):457-469. doi: 10.4103/ajns.AJNS_406_20

Massa S, Fracchiolla A, Neglia C, Argentiero A, Esposito S. Update on acute disseminated encephalomyelitis in children and adolescents. Children (Basel). 2021;8(4):280. doi: 10.3390/children8040280. doi: 10.3390/children8040280

Otallah S. Acute disseminated encephalomyelitis in children and adults: A focused review emphasizing new developments. Mult Scler.
2021;27(8):1153-1160. doi: 10.1177/1352458520929627

Wang CX. Assessment and management of acute disseminated encephalomyelitis (ADEM) in the pediatric patient. Paediatr Drugs. 2021;23(3):213-221. doi: 10.1007/s40272-021-00441-7

Yang JH, Vuong KT, Moodley A, Chuang NA, Chen DY. A case of tuberculosis-associated acute disseminated encephalomyelitis in a seven- month-old infant. Cureus. 2021;13(7):e16299. doi: 10.7759/cureus.16299

Paolilo RB, Deiva K, Neuteboom R, Rostásy K, Lim M. Acute disseminated encephalomyelitis: Current perspectives. Children (Basel). 2020;7(11):210. doi: 10.3390/children7110210. doi: 10.3390/children7110210

Cole J, Evans E, Mwangi M, Mar S. Acute disseminated encephalomyelitis in children: An updated review based on current diagnostic criteria. Pediatr Neurol. 2019;100:26-34. doi: S0887-8994(18)31161-5

Hara T. Acute disseminated encephalomyelitis (ADEM): Its diagnostic criteria and therapy. Nihon Rinsho. 2013;71(5):887-892.

Alper G. Acute disseminated encephalomyelitis. J Child Neurol. 2012;27(11):1408-1425. doi: 10.1177/0883073812455104

Pohl D, Tenembaum S. Treatment of acute disseminated encephalomyelitis. Curr Treat Options Neurol. 2012;14(3):264-275. doi: 10.1007/s11940-012-0170-0

Lassmann H. Acute disseminated encephalomyelitis and multiple sclerosis. Brain. 2010;133(2):317-319. doi: 10.1093/brain/awp342

Behan PO. Acute disseminated encephalomyelitis: Postinfectious, postimmunization and variant forms. Expert Rev Neurother. 2009;9(9):1321- 1329. doi: 10.1586/ern.09.90

Tenembaum SN. Disseminated encephalomyelitis in children. Clin Neurol Neurosurg. 2008;110(9):928-938. doi: 10.1016/j.clineuro.2007.12.018

Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: Current understanding and controversies. Semin Neurol. 2008;28(1):84-94. doi: 10.1055/s-2007-1019130

Krupp LB, Banwell B, Tenembaum S, International Pediatric MS Study Group. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology. 2007;68(16 Suppl 2):7. doi: 68/16_suppl_2/S7

Tenembaum S, Chitnis T, Ness J, Hahn JS, International Pediatric MS Study Group. Acute disseminated encephalomyelitis. Neurology. 2007;68(16 Suppl 2):23. doi: 68/16_suppl_2/S23

Love S. Demyelinating diseases. J Clin Pathol. 2006;59(11):1151-1159. doi: 59/11/1151

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(2):431- 436. doi: 116/2/431

Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood: Epidemiologic, clinical and laboratory features. Pediatr Infect Dis J. 2004;23(8):756-764. doi: 00006454-200408000-00010

Murthy SN, Faden HS, Cohen ME, Bakshi R. Acute disseminated encephalomyelitis in children. Pediatrics. 2002;110(2 Pt 1):e21. doi: 10.1542/peds.110.2.e21

Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: A long-term follow-up study of 84 pediatric
patients. Neurology. 2002;59(8):1224-1231. doi: 10.1212/wnl.59.8.1224

Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain. 2000;123 Pt 12:2407-2422. doi: 10.1093/brain/123.12.2407

INTERNET
Acute disseminated encephalomyelitis. Cleveland Clinic. Updated 2019.https://my.clevelandclinic.org/health/diseases/14266-acute- disseminated-encephalomyelitis-adem. Accessed June 22, 2022

National Institute of Neurological Disorders and Stroke. Acute Disseminated Encephalomyelitis. Last reviewed on May 03, 2022. Available at: https://www.ninds.nih.gov/health-information/disorders/acute-disseminated-encephalomyelitis Accessed June 22, 2022.

Brenton JN. Acute Disseminated Encephalomyelitis. Medscape. Updated: Nov 08, 2018. Available at: Acute Disseminated Encephalomyelitis: Background, Pathophysiology, Epidemiology (medscape.com) Accessed June 22, 2022.

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