Acute disseminated encephalomyelitis
|Acute disseminated encephalomyelitis|
|Classification and external resources|
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune disease marked by widespread attack of inflammation in the brain and spinal cord. ADEM typically damages the myelin sheaths covering the nerves of the central nervous system, which, as a result, destroys the white matter. It is often triggered after the patient has received a viral infection or vaccination.
ADEM's symptoms resemble the symptoms of multiple sclerosis (MS), so the disease itself is sorted into the classification of the multiple sclerosis borderline diseases. However, ADEM has several features that distinguish it from MS. Unlike MS, ADEM occurs usually in children and is marked with rapid fever, although adolescents and adults can get the disease too. ADEM consists of a single flare-up whereas MS is marked with several flare-ups over a long period of time. ADEM is also distinguished by a loss of consciousness, coma and death, which is very rare in MS, except in severe cases.
The incidence rate is about 8 per 1,000,000 people per year. Although it occurs in all ages, most reported cases are in children and adolescents, with the average age around 5 to 8 years old. The mortality rate may be as high as 5%; however, full recovery is seen in 50 to 75% of cases with increase in survival rates up to 70 to 90% with figures including minor residual disability as well. The average time to recover from ADEM flare-ups is one to six months.
ADEM produces multiple inflammatory lesions in the brain and spinal cord, particularly in the white matter. Usually these are found in the subcortical and central white matter and cortical gray-white junction of both cerebral hemispheres, cerebellum, brainstem, and spinal cord, but periventricular white matter and gray matter of the cortex, thalami and basal ganglia may also be involved.
- 1 Causes and antecedent history
- 2 Presentation
- 3 Treatment
- 4 Prognosis
- 5 ADEM and multiple sclerosis
- 6 Multiphasic disseminated encephalomyelitis
- 7 Acute hemorrhagic leukoencephalitis
- 8 Experimental allergic encephalomyelitis
- 9 See also
- 10 References
- 11 External links
Causes and antecedent history
Viral infections thought to induce ADEM include influenza virus, enterovirus, measles, mumps, rubella, varicella zoster, Epstein Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, and coxsackievirus; while the bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci. The only vaccine proven to induce ADEM is the Semple form of the rabies vaccine, but hepatitis B, pertussis, diphtheria, measles, mumps, rubella, pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been implicated. The majority of the studies that correlate vaccination with ADEM onset use small samples or case studies. Large scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination. In rare cases, ADEM seems to follow from organ transplantation. The risk of ADEM from measles vaccination is about 1 to 2 per million, which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1000 for measles (and 1 per 5000 for rubella). Some vaccines, later shown to have been contaminated with host animal CNS tissue, have ADEM incident rates as high as 1 in 600.
ADEM has an abrupt onset and a monophasic course. Symptoms usually begin 1–3 weeks after infection. Major symptoms include fever, headache, nausea and vomiting, confusion, vision impairment, drowsiness, seizures and coma. Although initially the symptoms are usually mild, they worsen rapidly over the course of hours to days, with the average time to maximum severity being about four and a half days. Additional symptoms include hemiparesis, paraparesis, and cranial nerve palsies.
No controlled clinical trials have been conducted on ADEM treatment, but aggressive treatment aimed at rapidly reducing inflammation of the CNS is standard. The widely accepted first-line treatment is high doses of intravenous corticosteroids, such as methylprednisolone or dexamethasone, followed by 3–6 weeks of gradually lower oral doses of prednisolone. Patients treated with methylprednisolone have shown better outcomes than those treated with dexamethasone. Oral tapers of less than three weeks duration show a higher chance of relapsing, and tend to show poorer outcomes. Other anti-inflammatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis, high doses of intravenous immunoglobulin (IVIg), mitoxantrone and cyclophosphamide. These are considered alternative therapies, used when corticosteroids cannot be used, or fail to show an effect.
There is some evidence to suggest that patients may respond to a combination of methylprednisolone and immunoglobulins if they fail to respond to either separately In a study of 16 children with ADEM, 10 recovered completely after high-dose methylprednisolone, one severe case that failed to respond to steroids recovered completely after IV Ig; the five most severe cases -with ADAM and severe peripheral neuropathy- were treated with combined high-dose methylprednisolone and immunoglobulin, two remained paraplegic, one had motor and cognitive handicaps, and two recovered. A recent review of IVIg treatment of ADEM (of which the previous study formed the bulk of the cases) found that 70% of children showed complete recovery after treatment with IVIg, or IVIg plus corticosteroids. A study of IVIg treatment in adults with ADEM showed that IVIg seems more effective in treating sensory and motor disturbances, while steroids seem more effective in treating impairments of cognition, consciousness and rigor. This same study found one subject, a 71-year-old man who had not responded to steroids, that responded to an IVIg treatment 58 days after disease onset.
Full recovery is seen in 50 to 70% of cases, ranging to 70 to 90% recovery with some minor residual disability (typically assessed using measures such as mRS or EDSS), average time to recover is one to six months. The mortality rate may be as high as 5%. Poorer outcomes are associated with unresponsiveness to steroid therapy, unusually severe neurological symptoms, or sudden onset. Children tend to have more favorable outcomes than adults, and cases presenting without fevers tend to have poorer outcomes. The latter effect may be due to either protective effects of fever, or that diagnosis and treatment is sought more rapidly when fever is present.
Patients with demyelinating illnesses, such as MS, have shown cognitive deficits even when there is minimal physical disability. Research suggests that similar effects are seen after ADEM, but that the deficits are less severe than those seen in MS. A study of six children with ADEM (mean age at presentation 7.7 years) were tested for a range of neurocognitive tests after an average of 3.5 years of recovery. All six children performed in the normal range on most tests, including verbal IQ and performance IQ, but performed at least one standard deviation below age norms in at least one cognitive domain, such as complex attention (one child), short-term memory (one child) and internalizing behaviour/affect (two children). Group means for each cognitive domain were all within one standard deviation of age norms, demonstrating that, as a group, they were normal. These deficits were less severe than those seen in similar aged children with a diagnosis of MS.
Another study compared nineteen children with a history of ADEM, of which 10 were five years of age or younger at the time (average age 3.8 years old, tested an average of 3.9 years later) and nine were older (mean age 7.7y at time of ADEM, tested an average of 2.2 years later) to nineteen matched controls. Scores on IQ tests and educational achievement were lower for the young onset ADEM group (average IQ 90) compared to the late onset (average IQ 100) and control groups (average IQ 106), while the late onset ADEM children scored lower on verbal processing speed. Again, all groups means were within one standard deviation of the controls, meaning that while effects were statistically reliable, the children were as a whole, still within the normal range. There were also more behavioural problems in the early onset group, although there is some suggestion that this may be due, at least in part, to the stress of hospitalization at a young age.
ADEM and multiple sclerosis
While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects. Some authors consider MS and its borderline forms to constitute a spectrum, differing only in chronicity, severity, and clinical course, while others consider them discretely different diseases.
Normally ADEM appears in children after a vaccination and it is monophasic. Nevertheless, ADEM can appear in adults, and can also be clinically multiphasic.
Problems for differential diagnosis increase due to the lack of agreement for a definition of Multiple Sclerosis. For some people MS should be considered a clinical entity based in inflammatory lesions separated in time and space. As some cases of ADEM satisfy these conditions, they can be considered inside the clinical MS spectrum.
The pathology of ADEM is very similar to that of MS with some differences. The pathological hallmark of ADEM is perivenular inflammation with limited ‘‘sleeves of demyelination.’’.
Plaques in the white matter in MS are sharply delineated, while the glial scar in ADEM is smooth. Axons are better preserved in ADEM lesions. Inflammation in ADEM is widely disseminated and ill-defined, and finally, lesions are strictly perivenous, while in MS they are disposed around veins, but not so sharply.
Nevertheless, the co-occurrence of perivenous and confluent demyelination in some individuals suggests pathogenic overlap between acute disseminated encephalomyelitis and multiple sclerosis and misclassification even with biopsy or even postmortem
Multiphasic disseminated encephalomyelitis
When the patient suffers more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis or multiphasic disseminated encephalomyelitis (MDEM).
Acute hemorrhagic leukoencephalitis
Acute hemorrhagic leukoencephalitis (AHL, or AHLE), also known as acute necrotizing encephalopathy (ANE), acute hemorrhagic encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE), Weston-Hurst syndrome, or Hurst's disease, is a hyperacute and frequently fatal form of ADEM. AHL is relatively rare (less than 100 cases have been reported in the medical literature as of 2006[update]), it is seen in about 2% of ADEM cases, and is characterized by necrotizing vasculitis of venules and hemorrhage, and edema. Death is common in the first week and overall mortality is about 70%, but increasing evidence points to favorable outcomes after aggressive treatment with corticosteroids, immunoglobulins, cyclophosphamide, and plasma exchange. About 70% of survivors show residual neurological deficits, but some survivors have shown surprisingly little deficit considering the magnitude of the white matter affected. This disease has been occasionally associated with ulcerative colitis and Crohn's disease, malaria, septicemia associated with immune complex deposition, methanol poisoning, and other underlying conditions.
Experimental allergic encephalomyelitis
Experimental allergic encephalomyelitis (EAE) is an animal model of CNS inflammation and demyelination frequently used to investigate potential MS treatments. An acute monophasic illness, EAE is far more similar to ADEM than MS.
- Dale RC (April 2003). "Acute disseminated encephalomyelitis". Semin Pediatr Infect Dis 14 (2): 90–5. doi:10.1053/spid.2003.127225. PMID 12881796.
- Garg RK (January 2003). "Acute disseminated encephalomyelitis". Postgrad Med J 79 (927): 11–7. doi:10.1136/pmj.79.927.11. PMC 1742586. PMID 12566545.
- Jones CT (November 2003). "Childhood autoimmune neurologic diseases of the central nervous system". Neurol Clin 21 (4): 745–64. doi:10.1016/S0733-8619(03)00007-0. PMID 14743647.
- Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C; Cordato; Kehdi; Masters; Dedousis (Dec 2008). "Post-vaccination encephalomyelitis: literature review and illustrative case". J Clin Neurosci 15 (12): :1315–1322. doi:10.1016/j.jocn.2008.05.002. PMID 18976924.
- Rust RS (June 2000). "Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions". Semin Pediatr Neurol 7 (2): 66–90. doi:10.1053/pb.2000.6693. PMID 10914409.
- Poser CM, Brinar VV; Brinar (October 2007). "Disseminated encephalomyelitis and multiple sclerosis: two different diseases - a critical review". Acta Neurol. Scand. 116 (4): 201–6. doi:10.1111/j.1600-0404.2007.00902.x. PMID 17824894.
- Lauren B. Krupp et al. Consensus definitions proposed for pediatric multiple sclerosis and related disorders, 2007 by AAN Enterprises, Inc. 
- Leake JA, Albani S, Kao AS et al. (August 2004). "Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features". Pediatr. Infect. Dis. J. 23 (8): 756–64. doi:10.1097/01.inf.0000133048.75452.dd. PMID 15295226.
- Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean MJ; Kornberg; Coleman; Shield; Harvey; Kean (May 2001). "Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children". Neurology 56 (10): 1308–12. doi:10.1212/WNL.56.10.1308. PMID 11376179.
- Anlar B, Basaran C, Kose G et al. (August 2003). "Acute disseminated encephalomyelitis in children: outcome and prognosis". Neuropediatrics 34 (4): 194–9. doi:10.1055/s-2003-42208. PMID 12973660.
- Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B; Mohr; Knauth; Wildemann; Storch-Hagenlocher (May 2001). "Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients". Neurology 56 (10): 1313–8. doi:10.1212/WNL.56.10.1313. PMID 11376180.
- Menge T, Kieseier BC, Nessler S, Hemmer B, Hartung HP, Stüve O; Kieseier; Nessler; Hemmer; Hartung; Stüve (June 2007). "Acute disseminated encephalomyelitis: an acute hit against the brain". Curr. Opin. Neurol. 20 (3): 247–54. doi:10.1097/WCO.0b013e3280f31b45. PMID 17495616.
- Wingerchuk DM (May 2003). "Postinfectious encephalomyelitis". Curr Neurol Neurosci Rep 3 (3): 256–64. doi:10.1007/s11910-003-0086-x. PMID 12691631.
- Poser CM (May 2008). "Multiple sclerosis and recurrent disseminated encephalomyelitis are different diseases". Arch. Neurol. 65 (5): 674; author reply 674–5. doi:10.1001/archneur.65.5.674-a. PMID 18474749.
- Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG; De Sousa; Chong; Cox; Harding; Neville (December 2000). "Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children". Brain 123 (12): 2407–22. doi:10.1093/brain/123.12.2407. PMID 11099444.
- Fisher, DL; Defres, S; Solomon, T (2015). "Measles-induced encephalitis". QJM 108 (3): 177–182. doi:10.1093/qjmed/hcu113. PMID 24865261.
- Tenembaum S, Chitnis T, Ness J, Hahn JS; Chitnis; Ness; Hahn; International Pediatric MS Study Group (April 2007). "Acute disseminated encephalomyelitis". Neurology 68 (16 Suppl 2): S23–36. doi:10.1212/01.wnl.0000259404.51352.7f. PMID 17438235.
- Hemachudha T, Griffin DE, Giffels JJ, Johnson RT, Moser AB, Phanuphak P; Griffin; Giffels; Johnson; Moser; Phanuphak (February 1987). "Myelin basic protein as an encephalitogen in encephalomyelitis and polyneuritis following rabies vaccination". N. Engl. J. Med. 316 (7): 369–74. doi:10.1056/NEJM198702123160703. PMID 2433582.
- Hemachudha T, Griffin DE, Johnson RT, Giffels JJ; Griffin; Johnson; Giffels (January 1988). "Immunologic studies of patients with chronic encephalitis induced by post-exposure Semple rabies vaccine". Neurology 38 (1): 42–4. doi:10.1212/WNL.38.1.42. PMID 2447520.
- Murthy JM (September 2002). "Acute disseminated encephalomyelitis". Neurol India 50 (3): 238–43. PMID 12391446.
- Tenembaum S, Chamoles N, Fejerman N; Chamoles; Fejerman (October 2002). "Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients". Neurology 59 (8): 1224–31. doi:10.1212/WNL.59.8.1224. PMID 12391351.
- Fenichel GM (August 1982). "Neurological complications of immunization". Ann. Neurol. 12 (2): 119–28. doi:10.1002/ana.410120202. PMID 6751212.
- Takahashi H, Pool V, Tsai1 TF, Chen RT; Pool; Tsai; Chen (July 2000). "Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group". Vaccine 18 (26): 2963–9. doi:10.1016/S0264-410X(00)00111-0. PMID 10825597.
- Tourbah A, Gout O, Liblau R et al. (July 1999). "Encephalitis after hepatitis B vaccination: recurrent disseminated encephalitis or MS?". Neurology 53 (2): 396–401. doi:10.1212/WNL.53.2.396. PMID 10430433.
- Karaali-Savrun F, Altintaş A, Saip S, Siva A; Altintaş; Saip; Siva (November 2001). "Hepatitis B vaccine related-myelitis?". Eur. J. Neurol. 8 (6): 711–5. doi:10.1046/j.1468-1331.2001.00290.x. PMID 11784358.
- Sejvar JJ, Labutta RJ, Chapman LE, Grabenstein JD, Iskander J, Lane JM; Labutta; Chapman; Grabenstein; Iskander; Lane (December 2005). "Neurologic adverse events associated with smallpox vaccination in the United States, 2002-2004". JAMA 294 (21): 2744–50. doi:10.1001/jama.294.21.2744. PMID 16333010.
- Ozawa H, Noma S, Yoshida Y, Sekine H, Hashimoto T; Noma; Yoshida; Sekine; Hashimoto (August 2000). "Acute disseminated encephalomyelitis associated with poliomyelitis vaccine". Pediatr. Neurol. 23 (2): 177–9. doi:10.1016/S0887-8994(00)00167-3. PMID 11020647.
- Miller HG, Stanton JB, Gibbons JL (1956). "Parainfectious encephalomyelitis and related syndromes". Quarterly Journal of Medicine 25 (100): 427–505. PMID 13379602.
- Allmendinger A, Krauthamer A, Spektor V (2009). "Case of the month". Diagnostic Imaging 31 (12): 10.
- Shahar E, Andraus J, Savitzki D, Pilar G, Zelnik N (November 2002). "Outcome of severe encephalomyelitis in children: effect of high-dose methylprednisolone and immunoglobulins". J. Child Neurol. 17 (11): 810–4. doi:10.1177/08830738020170111001. PMID 12585719.
- Ravaglia S, Piccolo G, Ceroni M et al. (November 2007). "Severe steroid-resistant post-infectious encephalomyelitis: general features and effects of IVIg". J. Neurol. 254 (11): 1518–23. doi:10.1007/s00415-007-0561-4. PMID 17965959.
- Straussberg R, Schonfeld T, Weitz R, Karmazyn B, Harel L (February 2001). "Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins". Pediatr. Neurol. 24 (2): 139–43. doi:10.1016/S0887-8994(00)00229-0. PMID 11275464.
- Feasby T, Banwell B, Benstead T et al. (April 2007). "Guidelines on the use of intravenous immune globulin for neurologic conditions". Transfus Med Rev 21 (2 Suppl 1): S57–107. doi:10.1016/j.tmrv.2007.01.002. PMID 17397768.
- Lin CH, Jeng JS, Hsieh ST, Yip PK, Wu RM (February 2007). "Acute disseminated encephalomyelitis: a follow-up study in Taiwan". J. Neurol. Neurosurg. Psychiatr. 78 (2): 162–7. doi:10.1136/jnnp.2005.084194. PMC 2077670. PMID 17028121.
- Foong J, Rozewicz L, Quaghebeur G et al. (January 1997). "Executive function in multiple sclerosis. The role of frontal lobe pathology". Brain 120 (1): 15–26. doi:10.1093/brain/120.1.15. PMID 9055794.
- Hahn CD, Miles BS, MacGregor DL, Blaser SI, Banwell BL, Hetherington CR (August 2003). "Neurocognitive outcome after acute disseminated encephalomyelitis". Pediatr. Neurol. 29 (2): 117–23. doi:10.1016/S0887-8994(03)00143-7. PMID 14580654.
- Banwell BL, Anderson PE (March 2005). "The cognitive burden of multiple sclerosis in children". Neurology 64 (5): 891–4. doi:10.1212/01.WNL.0000152896.35341.51. PMID 15753431.
- Jacobs RK, Anderson VA, Neale JL, Shield LK, Kornberg AJ (September 2004). "Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset". Pediatr. Neurol. 31 (3): 191–7. doi:10.1016/j.pediatrneurol.2004.03.008. PMID 15351018.
- Douglas JW (August 1975). "Early hospital admissions and later disturbances of behaviour and learning". Dev Med Child Neurol 17 (4): 456–80. doi:10.1111/j.1469-8749.1975.tb03497.x. PMID 1158052.
- Daviss WB, Racusin R, Fleischer A, Mooney D, Ford JD, McHugo GJ (May 2000). "Acute stress disorder symptomatology during hospitalization for pediatric injury". J Am Acad Child Adolesc Psychiatry 39 (5): 569–75. doi:10.1097/00004583-200005000-00010. PMID 10802974.
- Wingerchuk DM, Lucchinetti CF (June 2007). "Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis". Curr. Opin. Neurol. 20 (3): 343–50. doi:10.1097/WCO.0b013e3280be58d8. PMID 17495631.
- Weinshenker B, Miller D. (1999). Multiple sclerosis: one disease or many? In: Siva A, Kesselring J, Thompson A, eds. Frontiers in multiple sclerosis. London: Dunitz, p37-46.
- Hartung HP, Grossman RI (May 2001). "ADEM: distinct disease or part of the MS spectrum?". Neurology 56 (10): 1257–60. doi:10.1212/WNL.56.10.1257. PMID 11376169.
- Lauren B. Krupp et al, Consensus definitions proposed for pediatric multiple sclerosis and related disorders. NEUROLOGY 2007;68(Suppl 2):S7–S12
- Lassmann H. "Acute disseminated encephalomyelitis and multiple sclerosis". Brain 133: 317–319. doi:10.1093/brain/awp342.
- McDonald WI, Compston A, Edan G et al. (2001). "Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis". Ann. Neurol. 50 (1): 121–7. doi:10.1002/ana.1032. PMID 11456302.
- Nathan P. Young, Acute Disseminated Encephalomyelitis: Current Understanding and Controversies. Thieme Medical Publishers (Semin Neurol. 2008 Feb;28(1):84-94) 
- Lu Z, Zhang B, Qiu W, Kang Z, Shen L et al. (2011). "Comparative Brain Stem Lesions on MRI of Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, and Multiple Sclerosis". PLoS ONE 6 (8): e22766. doi:10.1371/journal.pone.0022766.
- Nathan P. et al. (2010). "Young et al. Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis". Brain 133: 333–348. doi:10.1093/brain/awp321.
- Guenther AD, Munoz DG (2013). "Plaque-like demyelination in acute disseminated encephalomyelitis (ADEM) - an autopsy case report". Clinical Neuropathology 32 (6): 486–491. doi:10.5414/NP300634. PMID 23863345.
- M. Baumann, E.M. Hennes, K. Schanda, M. Karenfort, B. Bajer-Kornek, K. Diepold, B. Fiedler, I. Marquardt, J. Strautmanis, S. Vieker, M. Reindl, K. Rostásy. Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies. European Journal of Paediatric Neurology, Volume 19, Supplement 1, May 2015, Pages S21, Abstracts of the 11th EPNS Congress. 22 May 2015. doi:10.1016/S1090-3798(15)30066-0
- Davies NW, Sharief MK, Howard RS; Sharief; Howard (July 2006). "Infection-associated encephalopathies: their investigation, diagnosis, and treatment". J. Neurol. 253 (7): 833–45. doi:10.1007/s00415-006-0092-4. PMID 16715200.
- Stone MJ, Hawkins CP; Hawkins (2007). "A medical overview of encephalitis". Neuropsychol Rehabil 17 (4–5): 429–49. doi:10.1080/09602010601069430. PMID 17676529.
- Archer H, Wall R; Wall (February 2003). "Acute haemorrhagic leukoencephalopathy: two case reports and review of the literature". J. Infect. 46 (2): 133–7. doi:10.1053/jinf.2002.1096. PMID 12634076.
- Venugopal V, Haider M; Haider (2013). "First case report of acute hemorrhagic leukoencephalitis following Plasmodium vivax infection". Indian J Med Microbiol 31 (1): 79–81. doi:10.4103/0255-0857.108736. PMID 23508437.
- Rivers TM, Schwentker FF; Schwentker (1935). "Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys". J. Exp. Med. 61 (5): 689–701. doi:10.1084/jem.61.5.689. PMC 2133246. PMID 19870385.
- Sriram S, Steiner I; Steiner (December 2005). "Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis". Ann. Neurol. 58 (6): 939–45. doi:10.1002/ana.20743. PMID 16315280.
- Acute Disseminated Encephalomyelitis (ADEM) at myelitis.org
- Acute disseminated encephalomyelitis at NIH's Office of Rare Diseases
- Acute Disseminated Encephalomyelitis Information Page at NINDS
- Information for parents about Acute disseminated encephalomyelitis