Acute disseminated encephalomyelitis

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.{{cite journal |vauthors = Allmendinger A, Krauthamer A, Spektor V | year = 2009 | title = Acute Disseminated Encephalomyelitis | series = Case of the month | url = http://www.diagnosticimaging.com/case-studies/content/article/113619/1493546 | archive-url = https://web.archive.org/web/20110224145009/http://www.diagnosticimaging.com/case-studies/content/article/113619/1493546 | archive-date = 24 February 2011 | journal = Diagnostic Imaging | volume = 31 | issue = 12| page = 10 }}

Neurological symptoms were the main presentation of COVID-19, which did not correlate with the severity of respiratory symptoms. The high incidence of ADEM with hemorrhage is striking. Brain inflammation is likely caused by an immune response to the disease rather than neurotropism. Cerebrospinal fluid analysis was not indicative of an infectious process, neurological impairment was not present in the acute phase of the infection, and neuroimaging findings were not typical of classical toxic and metabolic disorders. The finding of bilateral periventricular relatively asymmetrical lesions allied with deep white matter involvement, that may also be present in cortical gray-white matter junction, thalami, basal ganglia, cerebellum, and brainstem suggests an acute demyelination process.{{Cite journal | vauthors = Manikanta AK, Pradeep GV, Pydi R, Chanumolu AR, Joy LA, Kancherla N |date=2021-06-14|title=Acute Disseminated Encephalomyelitis in COVID 19- Systematic Review|url=https://www.annalsofrscb.ro/index.php/journal/article/view/7656|journal=Annals of the Romanian Society for Cell Biology|language=en|volume=25|issue=6|pages=11443–50}} Additionally, hemorrhagic white matter lesions, clusters of macrophages related to axonal injury and ADEM-like appearance were also found in subcortical white matter.{{cite journal | vauthors = Novi G, Rossi T, Pedemonte E, Saitta L, Rolla C, Roccatagliata L, Inglese M, Farinini D | display-authors = 6 | title = Acute disseminated encephalomyelitis after SARS-CoV-2 infection | journal = Neurology | volume = 7 | issue = 5 | date = September 2020 | pages = e797 | pmid = 32482781 | pmc = 7286650 | doi = 10.1212/NXI.0000000000000797 }}

Since the discovery of the anti-MOG specificity against multiple sclerosis diagnosis{{cite journal | vauthors = Reindl M, Di Pauli F, Rostásy K, Berger T | title = The spectrum of MOG autoantibody-associated demyelinating diseases | journal = Nature Reviews. Neurology | volume = 9 | issue = 8 | pages = 455–61 | date = August 2013 | pmid = 23797245 | doi = 10.1038/nrneurol.2013.118 | s2cid = 7219279 }} it is considered that ADEM is one of the possible clinical causes of anti-MOG associated encephalomyelitis.{{cite journal | vauthors = Weber MS, Derfuss T, Brück W | title = Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Central Nervous System Demyelination-A Novel Disease Entity? | journal = JAMA Neurology | volume = 75 | issue = 8 | pages = 909–10 | date = August 2018 | pmid = 29913011 | doi = 10.1001/jamaneurol.2018.1055 | s2cid = 49303770 }}

There are several theories about how the anti-MOG antibodies appear in the patient's serum:

• A preceding antigenic challenge can be identified in approximately two-thirds of people. Some viral infections thought to induce ADEM include influenza virus, dengue,{{cite journal | vauthors = Kamel MG, Nam NT, Han NH, El-Shabouny AE, Makram AM, Abd-Elhay FA, Dang TN, Hieu NL, Huong VT, Tung TH, Hirayama K, Huy NT | editor-first1 = Ruifu | editor-last1 = Yang | display-authors = 6 | title = Post-dengue acute disseminated encephalomyelitis: A case report and meta-analysis | journal = PLOS Neglected Tropical Diseases | volume = 11 | issue = 6 | pages = e0005715 | date = June 2017 | pmid = 28665957 | pmc = 5509372 | doi = 10.1371/journal.pntd.0005715 | doi-access = free }} enterovirus, measles,{{cite journal | vauthors = Fisher DL, Defres S, Solomon T | title = Measles-induced encephalitis | journal = QJM | volume = 108 | issue = 3 | pages = 177–82 | date = March 2015 | pmid = 24865261 | doi = 10.1093/qjmed/hcu113 | doi-access = free }} mumps, rubella, varicella zoster, Epstein–Barr virus, cytomegalovirus, herpes simplex virus, hepatitis A, coxsackievirus and COVID-19.{{cite news| vauthors = Sample I |date=2020-07-08|title=Warning of serious brain disorders in people with mild coronavirus symptoms|language=en-GB|work=The Guardian|url=https://www.theguardian.com/world/2020/jul/08/warning-of-serious-brain-disorders-in-people-with-mild-covid-symptoms|access-date=2020-07-08|issn=0261-3077}} Bacterial infections include Mycoplasma pneumoniae, Borrelia burgdorferi, Leptospira, and beta-hemolytic Streptococci.{{cite journal | vauthors = Tenembaum S, Chitnis T, Ness J, Hahn JS | title = Acute disseminated encephalomyelitis | journal = Neurology | volume = 68 | issue = 16 Suppl 2 | pages = S23–36 | date = April 2007 | pmid = 17438235 | doi = 10.1212/01.wnl.0000259404.51352.7f | s2cid = 19893165 | others = International Pediatric MS Study Group }}
• Exposure to vaccines: The only vaccine proven related to ADEM is the Semple form of the rabies vaccine, but hepatitis B,{{cite journal | vauthors = Karaali-Savrun F, Altintaş A, Saip S, Siva A | title = Hepatitis B vaccine related-myelitis? | journal = European Journal of Neurology | volume = 8 | issue = 6 | pages = 711–15 | date = November 2001 | pmid = 11784358 | doi = 10.1046/j.1468-1331.2001.00290.x | s2cid = 30784630 }} pertussis, diphtheria, measles, mumps, rubella,{{cite journal | last1=Kania | first1=Karolina | last2=Ambrosius | first2=Wojciech | last3=Tokarz Kupczyk | first3=Elzbieta | last4=Kozubski | first4=Wojciech | title=Acute disseminated encephalomyelitis in a patient vaccinated against SARS-CoV-2 | journal=Annals of Clinical and Translational Neurology | volume=8 | issue=10 | date=2021 | issn=2328-9503 | pmid=34480527 | pmc=8528462 | doi=10.1002/acn3.51447 | pages=2000–2003}} pneumococcus, varicella, influenza, Japanese encephalitis, and polio vaccines have all been associated with the condition. {{cite journal | vauthors = Huynh W, Cordato DJ, Kehdi E, Masters LT, Dedousis C | title = Post-vaccination encephalomyelitis: literature review and illustrative case | journal = Journal of Clinical Neuroscience | volume = 15 | issue = 12 | pages = 1315–22 | date = December 2008 | pmid = 18976924 | pmc = 7125578 | doi = 10.1016/j.jocn.2008.05.002 }}{{cite journal |vauthors=Rust RS |title=Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions |journal=Seminars in Pediatric Neurology |volume=7 |issue=2 |pages=66–90 |date=June 2000 |pmid=10914409 |doi= 10.1053/pb.2000.6693}} The majority of the studies that correlate vaccination with ADEM onset use only small samples or are case studies.{{cite journal | last=Tenembaum | first=Silvia N. | title=Disseminated encephalomyelitis in children | journal=Clinical Neurology and Neurosurgery | publisher=Elsevier BV | volume=110 | issue=9 | year=2008 | issn=0303-8467 | doi=10.1016/j.clineuro.2007.12.018 | pages=928–938| pmid=18272282 | pmc=7116932 }} Large-scale epidemiological studies (e.g., of MMR vaccine or smallpox vaccine) do not show increased risk of ADEM following vaccination.{{cite journal | vauthors = Hemachudha T, Griffin DE, Giffels JJ, Johnson RT, Moser AB, Phanuphak P | title = Myelin basic protein as an encephalitogen in encephalomyelitis and polyneuritis following rabies vaccination | journal = The New England Journal of Medicine | volume = 316 | issue = 7 | pages = 369–74 | date = February 1987 | pmid = 2433582 | doi = 10.1056/NEJM198702123160703 }}{{cite journal | vauthors = Hemachudha T, Griffin DE, Johnson RT, Giffels JJ | title = Immunologic studies of patients with chronic encephalitis induced by post-exposure Semple rabies vaccine | journal = Neurology | volume = 38 | issue = 1 | pages = 42–44 | date = January 1988 | pmid = 2447520 | doi = 10.1212/WNL.38.1.42 | s2cid = 21992894 }}{{cite journal | vauthors = Murthy JM | title = Acute disseminated encephalomyelitis | journal = Neurology India | volume = 50 | issue = 3 | pages = 238–43 | date = September 2002 | pmid = 12391446 | url = http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2002;volume=50;issue=3;spage=238;epage=43;aulast=Murthy }}{{cite journal | vauthors = Tenembaum S, Chamoles N, Fejerman N | title = Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients | journal = Neurology | volume = 59 | issue = 8 | pages = 1224–31 | date = October 2002 | pmid = 12391351 | doi = 10.1212/WNL.59.8.1224 | s2cid = 37405227 }}{{cite journal | vauthors = Fenichel GM | title = Neurological complications of immunization | journal = Annals of Neurology | volume = 12 | issue = 2 | pages = 119–28 | date = August 1982 | pmid = 6751212 | doi = 10.1002/ana.410120202 | s2cid = 2352985 }}{{cite journal | vauthors = Takahashi H, Pool V, Tsai TF, Chen RT | title = Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group | journal = Vaccine | volume = 18 | issue = 26 | pages = 2963–69 | date = July 2000 | pmid = 10825597 | doi = 10.1016/S0264-410X(00)00111-0 | url = https://zenodo.org/record/1259957 }}{{cite journal | vauthors = Tourbah A, Gout O, Liblau R, Lyon-Caen O, Bougniot C, Iba-Zizen MT, Cabanis EA | title = Encephalitis after hepatitis B vaccination: recurrent disseminated encephalitis or MS? | journal = Neurology | volume = 53 | issue = 2 | pages = 396–401 | date = July 1999 | pmid = 10430433 | doi = 10.1212/WNL.53.2.396 | s2cid = 25061061 }}{{cite journal | vauthors = Sejvar JJ, Labutta RJ, Chapman LE, Grabenstein JD, Iskander J, Lane JM | title = Neurologic adverse events associated with smallpox vaccination in the United States, 2002–2004 | journal = JAMA | volume = 294 | issue = 21 | pages = 2744–50 | date = December 2005 | pmid = 16333010 | doi = 10.1001/jama.294.21.2744 | doi-access = }}{{cite journal | vauthors = Ozawa H, Noma S, Yoshida Y, Sekine H, Hashimoto T | title = Acute disseminated encephalomyelitis associated with poliomyelitis vaccine | journal = Pediatric Neurology | volume = 23 | issue = 2 | pages = 177–79 | date = August 2000 | pmid = 11020647 | doi = 10.1016/S0887-8994(00)00167-3 }} An upper bound for the risk of ADEM from measles vaccination, if it exists, can be estimated to be 10 per million,{{cite book|title=Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality| vauthors = Stratton KR, Howe CJ, Johnston Jr RB |date=1994|publisher=The National Academies Press|isbn=978-0-309-07496-4|pages=125–26| doi = 10.17226/2138 | pmid = 25144097 |url=http://www.nap.edu/read/2138/chapter/7#124|access-date=6 December 2015| collaboration = Institute of Medicine (US) Vaccine Safety Committee }} which is far lower than the risk of developing ADEM from an actual measles infection, which is about 1 per 1,000 cases. For a rubella infection, the risk is 1 per 5,000 cases.{{cite journal | vauthors = Gibbons JL, Miller HG, Stanton JB | title = Para-infectious encephalomyelitis and related syndromes; a critical review of the neurological complications of certain specific fevers | journal = The Quarterly Journal of Medicine | volume = 25 | issue = 100 | pages = 427–505 | date = October 1956 | pmid = 13379602 }} Some early vaccines, later shown to have been contaminated with host animal central nervous system tissue, had ADEM incidence rates as high as 1 in 600.
• In rare cases, ADEM seems to follow from organ transplantation.

The term ADEM has been inconsistently used at different times.{{cite journal | vauthors = Cole J, Evans E, Mwangi M, Mar S | title = Acute Disseminated Encephalomyelitis in Children: An Updated Review Based on Current Diagnostic Criteria | journal = Pediatric Neurology | volume = 100 | issue = | pages = 26–34 | date = November 2019 | pmid = 31371120 | doi = 10.1016/j.pediatrneurol.2019.06.017 | s2cid = 198267007 }} Currently, the commonly accepted international standard for the clinical case definition is the one published by the International Pediatric MS Study Group, revision 2007.{{cite journal | vauthors = Tenembaum S, Chitnis T, Ness J, Hahn JS | title = Acute disseminated encephalomyelitis | journal = Neurology | volume = 68 | issue = 16 Suppl 2 | pages = S23–36 | date = April 2007 | pmid = 17438235 | doi = 10.1212/01.wnl.0000259404.51352.7f | s2cid = 19893165 }}

Given that the definition is clinical, it is currently unknown if all the cases of ADEM are positive for anti-MOG autoantibody; in any case, it appears to be strongly related to ADEM diagnosis.

While ADEM and MS both involve autoimmune demyelination, they differ in many clinical, genetic, imaging, and histopathological aspects.{{cite journal | vauthors = Wingerchuk DM, Lucchinetti CF | title = Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis | journal = Current Opinion in Neurology | volume = 20 | issue = 3 | pages = 343–50 | date = June 2007 | pmid = 17495631 | doi = 10.1097/WCO.0b013e3280be58d8 | s2cid = 17386506 }} Some authors consider MS and its borderline forms to constitute a spectrum, differing only in chronicity, severity, and clinical course,{{cite book | vauthors = Weinshenker B, Miller D | date = 1999 | chapter = Multiple sclerosis: one disease or many? | veditors = Siva A, Kesselring J, Thompson A | title = Frontiers in multiple sclerosis | location = London | publisher = Dunitz | pages = 37–46 | isbn = 978-1-85317-506-0 }}{{cite journal | vauthors = Hartung HP, Grossman RI | title = ADEM: distinct disease or part of the MS spectrum? | journal = Neurology | volume = 56 | issue = 10 | pages = 1257–60 | date = May 2001 | pmid = 11376169 | doi = 10.1212/WNL.56.10.1257 | s2cid = 219199163 }} while others consider them discretely different diseases.

Typically, ADEM appears in children following an antigenic challenge and remains monophasic. Nevertheless, ADEM does occur in adults, and can also be clinically multiphasic.{{cite journal | vauthors = Krupp LB, Banwell B, Tenembaum S | collaboration = International Pediatric MS Study Group | title = Consensus definitions proposed for pediatric multiple sclerosis and related disorders | journal = Neurology | volume = 68 | issue = 16 Suppl 2 | pages = S7–12 | date = April 2007 | pmid = 17438241 | doi = 10.1212/01.wnl.0000259422.44235.a8 | s2cid = 26001350 }}

Problems for differential diagnosis increase due to the lack of agreement for a definition of multiple sclerosis.{{cite journal | vauthors = Lassmann H | title = Acute disseminated encephalomyelitis and multiple sclerosis | journal = Brain | volume = 133 | issue = Pt 2 | pages = 317–19 | date = February 2010 | pmid = 20129937 | doi = 10.1093/brain/awp342 | doi-access = free }} If MS were defined only by the separation in time and space of the demyelinating lesions as McDonald did,{{cite journal | vauthors = McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS | display-authors = 6 | title = Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis | journal = Annals of Neurology | volume = 50 | issue = 1 | pages = 121–27 | date = July 2001 | pmid = 11456302 | doi = 10.1002/ana.1032 | author2-link = Alastair Compston | s2cid = 13870943 | citeseerx = 10.1.1.466.5368 | author1-link = W. Ian McDonald }} it would not be enough to make a difference, as some cases of ADEM satisfy these conditions. Therefore, some authors propose to establish the dividing line as the shape of the lesions around the veins, being therefore "perivenous vs. confluent demyelination".{{cite journal | vauthors = Young NP, Weinshenker BG, Parisi JE, Scheithauer B, Giannini C, Roemer SF, Thomsen KM, Mandrekar JN, Erickson BJ, Lucchinetti CF | display-authors = 6 | title = Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis | journal = Brain | volume = 133 | issue = Pt 2 | pages = 333–48 | date = February 2010 | pmid = 20129932 | pmc = 2822631 | doi = 10.1093/brain/awp321 | doi-access = free }}

File:Acute hemorrhagic Leukoencephalitis in a patient with Multiple sclerosis (MRI).png

The pathology of ADEM is very similar to that of MS with some differences. The pathological hallmark of ADEM is perivenous inflammation with limited "sleeves of demyelination".{{cite journal | vauthors = Young NP, Weinshenker BG, Lucchinetti CF | title = Acute Disseminated Encephalomyelitis: Current Understanding and Controversies | journal = Seminars in Neurology | volume = 28 | issue = 1 | pages = 84–94 | date = February 2008 | pmid = 18256989 | doi = 10.1055/s-2007-1019130 | doi-access = free }} Nevertheless, MS-like plaques (confluent demyelination) can appear{{cite journal | vauthors = Guenther AD, Munoz DG | title = Plaque-like demyelination in acute disseminated encephalomyelitis (ADEM) – an autopsy case report | journal = Clinical Neuropathology | volume = 32 | issue = 6 | pages = 486–91 | year = 2013 | pmid = 23863345 | doi = 10.5414/NP300634 }}

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.{{cite journal | vauthors = Lu Z, Zhang B, Qiu W, Kang Z, Shen L, Long Y, Huang J, Hu X | editor-first1 = Pablo | editor-last1 = Villoslada | display-authors = 6 | title = Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis | journal = PLOS ONE | volume = 6 | issue = 8 | pages = e22766 | year = 2011 | pmid = 21853047 | pmc = 3154259 | doi = 10.1371/journal.pone.0022766 | doi-access = free | bibcode = 2011PLoSO...622766L }}

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 ADEM in adults can progress to MS

When the person has more than one demyelinating episode of ADEM, the disease is then called recurrent disseminated encephalomyelitis or multiphasic disseminated encephalomyelitis (MDEM).

It has been found that anti-MOG auto-antibodies are related to this kind of ADEM{{cite journal | vauthors = Baumann M, Hennes EM, Schanda K, Karenfort M, Bajer-Kornek B, Diepold K, Fiedler B, Marquardt I, Strautmanis J, Vieker S, Reindl M | display-authors = 6 | title = OP65–3006: Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies. | journal = European Journal of Paediatric Neurology | date = May 2015 | volume = 19 | issue = supplement 1 | pages = S21 | doi = 10.1016/S1090-3798(15)30066-0 | series = Abstracts of the 11th EPNS Congress }}

Another variant of ADEM in adults has been described, also related to anti-MOG auto-antibodies, has been named fulminant disseminated encephalomyelitis, and it has been reported to be clinically ADEM, but showing MS-like lesions on autopsy. It has been classified inside the anti-MOG associated inflammatory demyelinating diseases.{{cite journal | vauthors = Baumann M, Hennes EM, Schanda K, Karenfort M, Kornek B, Seidl R, Diepold K, Lauffer H, Marquardt I, Strautmanis J, Syrbe S, Vieker S, Höftberger R, Reindl M, Rostásy K | display-authors = 6 | title = Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases | journal = Multiple Sclerosis | volume = 22 | issue = 14 | pages = 1821–29 | date = December 2016 | pmid = 26869530 | doi = 10.1177/1352458516631038 | s2cid = 30428892 }}

Acute hemorrhagic leukoencephalitis (AHL, or AHLE), 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|lc=y}}),{{cite journal | vauthors = Davies NW, Sharief MK, Howard RS | title = Infection-associated encephalopathies: their investigation, diagnosis, and treatment | journal = Journal of Neurology | volume = 253 | issue = 7 | pages = 833–45 | date = July 2006 | pmid = 16715200 | doi = 10.1007/s00415-006-0092-4 | s2cid = 26350300 | doi-access = free }} it is seen in about 2% of ADEM cases, and is characterized by necrotizing vasculitis of venules and hemorrhage, and edema.{{cite journal | vauthors = Stone MJ, Hawkins CP | title = A medical overview of encephalitis | journal = Neuropsychological Rehabilitation | volume = 17 | issue = 4–5 | pages = 429–49 | year = 2007 | pmid = 17676529 | doi = 10.1080/09602010601069430 | s2cid = 24249705 }} Death is common in the first week{{cite journal | vauthors = Archer H, Wall R | title = Acute haemorrhagic leukoencephalopathy: two case reports and review of the literature | journal = The Journal of Infection | volume = 46 | issue = 2 | pages = 133–37 | date = February 2003 | pmid = 12634076 | doi = 10.1053/jinf.2002.1096 }} 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 extent of the white matter affected.

This disease has been occasionally associated with ulcerative colitis and Crohn's disease, malaria,{{cite journal | vauthors = Venugopal V, Haider M | title = First case report of acute hemorrhagic leukoencephalitis following Plasmodium vivax infection | journal = Indian Journal of Medical Microbiology | volume = 31 | issue = 1 | pages = 79–81 | year = 2013 | pmid = 23508437 | doi = 10.4103/0255-0857.108736 | doi-access = free }} sepsis associated with immune complex deposition, methanol poisoning, and other underlying conditions. Also anecdotal association with MS has been reported{{cite journal | vauthors = Yildiz Ö, Pul R, Raab P, Hartmann C, Skripuletz T, Stangel M | title = Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis | journal = Journal of Neuroinflammation | volume = 12 | issue = 1 | pages = 175 | date = September 2015 | pmid = 26376717 | pmc = 4574135 | doi = 10.1186/s12974-015-0398-1 | doi-access = free }}

Laboratory studies that support diagnosis of AHL are: peripheral leukocytosis, cerebrospinal fluid (CSF) pleocytosis associated with normal glucose and increased protein. On magnetic resonance imaging (MRI), lesions of AHL typically show extensive T2-weighted and fluid-attenuated inversion recovery (FLAIR) white matter hyperintensities with areas of hemorrhages, significant edema, and mass effect.{{cite journal | vauthors = Mondia MW, Reyes NG, Espiritu AI, Pascual V JL | title = Acute hemorrhagic leukoencephalitis of Weston Hurst secondary to herpes encephalitis presenting as status epilepticus: A case report and review of literature | journal = Journal of Clinical Neuroscience | volume = 67 | issue = | pages = 265–70 | date = September 2019 | pmid = 31239199 | doi = 10.1016/j.jocn.2019.06.020 | s2cid = 195261409 }}

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.{{citation needed|date=March 2008}} Other anti-inflammatory and immunosuppressive therapies have been reported to show beneficial effect, such as plasmapheresis, high doses of intravenous immunoglobulin (IVIg),{{cite journal | vauthors = Shahar E, Andraus J, Savitzki D, Pilar G, Zelnik N | title = Outcome of severe encephalomyelitis in children: effect of high-dose methylprednisolone and immunoglobulins | journal = Journal of Child Neurology | volume = 17 | issue = 11 | pages = 810–14 | date = November 2002 | pmid = 12585719 | doi = 10.1177/08830738020170111001 | s2cid = 25519230 }}{{cite journal | vauthors = Ravaglia S, Piccolo G, Ceroni M, Franciotta D, Pichiecchio A, Bastianello S, Tavazzi E, Minoli L, Marchioni E | display-authors = 6 | title = Severe steroid-resistant post-infectious encephalomyelitis: general features and effects of IVIg | journal = Journal of Neurology | volume = 254 | issue = 11 | pages = 1518–23 | date = November 2007 | pmid = 17965959 | doi = 10.1007/s00415-007-0561-4 | s2cid = 21922460 }} mitoxantrone and cyclophosphamide. These are considered alternative therapies, used when corticosteroids cannot be used or fail to show an effect.{{citation needed|date=August 2020}}

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{{cite journal | vauthors = Straussberg R, Schonfeld T, Weitz R, Karmazyn B, Harel L | title = Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins | journal = Pediatric Neurology | volume = 24 | issue = 2 | pages = 139–43 | date = February 2001 | pmid = 11275464 | doi = 10.1016/S0887-8994(00)00229-0 }}

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.{{cite journal | vauthors = Feasby T, Banwell B, Benstead T, Bril V, Brouwers M, Freedman M, Hahn A, Hume H, Freedman J, Pi D, Wadsworth L | display-authors = 6 | title = Guidelines on the use of intravenous immune globulin for neurologic conditions | journal = Transfusion Medicine Reviews | volume = 21 | issue = 2 Suppl 1 | pages = S57–107 | date = April 2007 | pmid = 17397768 | doi = 10.1016/j.tmrv.2007.01.002 }} 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.{{citation needed|date=August 2020}}

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 5–10%.{{cite journal | vauthors = Kamel MG, Nam NT, Han NH, El-Shabouny AE, Makram AM, Abd-Elhay FA, Dang TN, Hieu NL, Huong VT, Tung TH, Hirayama K, Huy NT | editor-first1 = Ruifu | editor-last1 = Yang | display-authors = 6 | title = Post-dengue acute disseminated encephalomyelitis: A case report and meta-analysis | journal = PLOS Neglected Tropical Diseases | volume = 11 | issue = 6 | pages = e0005715 | date = June 2017 | pmid = 28665957 | pmc = 5509372 | doi = 10.1371/journal.pntd.0005715 | doi-access = free }} 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. {{cite journal | vauthors = Lin CH, Jeng JS, Hsieh ST, Yip PK, Wu RM | title = Acute disseminated encephalomyelitis: a follow-up study in Taiwan | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 78 | issue = 2 | pages = 162–67 | date = February 2007 | pmid = 17028121 | pmc = 2077670 | doi = 10.1136/jnnp.2005.084194 }}

ADEM can progress to MS. It will be considered MS if some lesions appear in different times and brain areas{{cite journal | vauthors = Malo-Pion C, Lambert R, Décarie JC, Turpin S | title = Imaging of Acquired Demyelinating Syndrome With 18F-FDG PET/CT | journal = Clinical Nuclear Medicine | volume = 43 | issue = 2 | pages = 103–05 | date = February 2018 | pmid = 29215409 | doi = 10.1097/RLU.0000000000001916 }}

Residual motor deficits are estimated to remain in about 8 to 30% of cases, the range in severity from mild clumsiness to ataxia and hemiparesis.

Patients with demyelinating illnesses, such as MS, have shown cognitive deficits even when there is minimal physical disability.{{cite journal | vauthors = Foong J, Rozewicz L, Quaghebeur G, Davie CA, Kartsounis LD, Thompson AJ, Miller DH, Ron MA | display-authors = 6 | title = Executive function in multiple sclerosis. The role of frontal lobe pathology | journal = Brain | volume = 120 | issue = 1 | pages = 15–26 | date = January 1997 | pmid = 9055794 | doi = 10.1093/brain/120.1.15 | doi-access = free }} 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.{{cite journal | vauthors = Hahn CD, Miles BS, MacGregor DL, Blaser SI, Banwell BL, Hetherington CR | title = Neurocognitive outcome after acute disseminated encephalomyelitis | journal = Pediatric Neurology | volume = 29 | issue = 2 | pages = 117–23 | date = August 2003 | pmid = 14580654 | doi = 10.1016/S0887-8994(03)00143-7 }} 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.{{cite journal | vauthors = Banwell BL, Anderson PE | title = The cognitive burden of multiple sclerosis in children | journal = Neurology | volume = 64 | issue = 5 | pages = 891–94 | date = March 2005 | pmid = 15753431 | doi = 10.1212/01.WNL.0000152896.35341.51 | s2cid = 6532050 }}

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.{{cite journal | vauthors = Jacobs RK, Anderson VA, Neale JL, Shield LK, Kornberg AJ | title = Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset | journal = Pediatric Neurology | volume = 31 | issue = 3 | pages = 191–97 | date = September 2004 | pmid = 15351018 | doi = 10.1016/j.pediatrneurol.2004.03.008 }} 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.{{cite journal | vauthors = Douglas JW | title = Early hospital admissions and later disturbances of behaviour and learning | journal = Developmental Medicine and Child Neurology | volume = 17 | issue = 4 | pages = 456–80 | date = August 1975 | pmid = 1158052 | doi = 10.1111/j.1469-8749.1975.tb03497.x | s2cid = 19270009 }}{{cite journal | vauthors = Daviss WB, Racusin R, Fleischer A, Mooney D, Ford JD, McHugo GJ | title = Acute stress disorder symptomatology during hospitalization for pediatric injury | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 39 | issue = 5 | pages = 569–75 | date = May 2000 | pmid = 10802974 | doi = 10.1097/00004583-200005000-00010 }}

The relationship between ADEM and anti-MOG associated encephalomyelitis is currently under research. A new entity called MOGDEM has been proposed.{{cite journal | vauthors = Misu T, Fujihara K | title = Neuromyelitis optica spectrum and myelin oligodendrocyte glycoprotein antibody-related disseminated encephalomyelitis. | journal = Clinical and Experimental Neuroimmunology | date = February 2019 | volume = 10 | issue = 1 | pages = 9–17 | doi = 10.1111/cen3.12491 | s2cid = 59566930 }}

About animal models, the main animal model for MS, experimental autoimmune encephalomyelitis (EAE) is also an animal model for ADEM.{{cite journal | vauthors = Rivers TM, Schwentker FF | title = Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys | journal = The Journal of Experimental Medicine | volume = 61 | issue = 5 | pages = 689–702 | date = April 1935 | pmid = 19870385 | pmc = 2133246 | doi = 10.1084/jem.61.5.689 }} Being an acute monophasic illness, EAE is far more similar to ADEM than MS.{{cite journal | vauthors = Sriram S, Steiner I | title = Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis | journal = Annals of Neurology | volume = 58 | issue = 6 | pages = 939–45 | date = December 2005 | pmid = 16315280 | doi = 10.1002/ana.20743 | s2cid = 12141651 | doi-access = free }}

• Optic neuritis
• Transverse myelitis
• Meningitis-retention syndrome
• Victoria Arlen

{{Reflist}}

• {{Office of Rare Diseases|8639|Acute disseminated encephalomyelitis}}
• {{NINDS|acute-disseminated-encephalomyelitis|Acute Disseminated Encephalomyelitis}}
• [https://wearesrna.org/living-with-myelitis/disease-information/acute-disseminated-encephalomyelitis Acute Disseminated Encephalomyelitis], Siegel Rare Neuroimmune Association
• [https://archive.today/20140609132223/http://www.gosh.nhs.uk/medical-conditions/search-for-medical-conditions/acute-disseminated-encephalomyelitis/acute-disseminated-encephalomyelitis-information/ Information for parents about Acute disseminated encephalomyelitis], Great Ormond Street Hospital

{{Medical resources

| DiseasesDB = 158

| ICD10 = {{ICD10|G|04|0|g|00}}

| ICD9 = {{ICD9|323.61}}, {{ICD9|323.81}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj = neuro

| eMedicineTopic = 500

| MeshID = D004673

|Orphanet=83597|ICD11={{ICD11|8A42}}|NORD=acute-disseminated-encephalomyelitis|GARDNum=8639|GARDName=acute-disseminated-encephalomyelitis|RP=acute-disseminated-encephalomyelitis-adem}}

{{Multiple sclerosis}}

{{Diseases of the nervous system}}

Category:Multiple sclerosis

Category:Autoimmune diseases

Category:Central nervous system disorders

Category:Enterovirus-associated diseases

Category:Measles

Category:Rare diseases