Acute disseminated encephalomyelitis (ADEM) was originally described in the medical literature more than 200 years ago. However, consensus clinical diagnostic criteria are less than 15 years old. Accurate diagnostic testing for myelin oligodendrocyte glycoprotein (MOG) autoantibodies has only become clinically available in the last 3–5 years and has facilitated a rapidly evolving understanding of patients with recurrent demyelination following ADEM. The field is working to optimize treatment for these patients with hopes of prospective treatment studies in the not too distant future. New imaging data suggest that even monophasic demyelination may have long-term impacts that were previously unrecognized. Recent developments in the literature are described in order to guide practice for providers who treat both adults and children with monophasic and recurrent forms of ADEM with and without MOG antibodies.
LucasJ.An account of uncommon symptoms succeeding the measles with additional remarks on the infection of measles and smallpox. London Med J1790; 11: 325–333.
2.
SchwarzSMohrAKnauthM, et al. Acute disseminated encephalomyelitis: A follow-up study of 40 adult patients. Neurology2001; 56: 1313–1318.
3.
DaleRCde SousaCChongWK, et al. Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain2000; 123(Pt. 12): 2407–2422.
4.
BhattPBrayLRajuS, et al. Temporal trends of pediatric hospitalizations with acute disseminated encephalomyelitis in the United States: An analysis from 2006 to 2014 using national inpatient sample. J Pediatr2019; 206: 26–32.
5.
YamaguchiYTorisuHKiraR, et al. A nationwide survey of pediatric acquired demyelinating syndromes in Japan. Neurology2016; 87: 2006–2015.
6.
ChenYMaFXuY, et al. Incidence of acute disseminated encephalomyelitis in the Jiangsu province of China, 2008-2011. Mult Scler J Exp Transl Clin2015; 1: 2055217315594831.
7.
de MolCLWongYvan PeltED, et al. The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults. Mult Scler2020; 26(7): 806–814.
8.
KruppLBTardieuMAmatoMP, 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 Scler2013; 19(10): 1261–1267.
9.
BoesenMSBlinkenbergMKoch-HenriksenN, et al. Implications of the international paediatric multiple sclerosis study group consensus criteria for paediatric acute disseminated encephalomyelitis: A nationwide validation study. Dev Med Child Neurol2018; 60(11): 1123–1131.
10.
KoelmanDLChahinSMarSS, et al. Acute disseminated encephalomyelitis in 228 patients: A retrospective, multicenter US study. Neurology2016; 86: 2085–2093.
GiriPPBhattyacharyaSDasD, et al. Acute disseminated encephalomyelitis: A clinical and neuroradiological profile of pediatric patients. Neurol India2016; 64(6): 1187–1192.
13.
KetelslegersIAVisserIENeuteboomRF, et al. Disease course and outcome of acute disseminated encephalomyelitis is more severe in adults than in children. Mult Scler2011; 17(4): 441–448.
14.
BaxterRLewisEGoddardK, et al. Acute demyelinating events following vaccines: A case-centered analysis. Clin Infect Dis2016; 63: 1456–1462.
15.
NishiyamaMNagaseHTomiokaK, et al. Clinical time course of pediatric acute disseminated encephalomyelitis. Brain Dev2019; 41(6): 531–537.
TenembaumSChitnisTNessJ, et al. Acute disseminated encephalomyelitis. Neurology2007; 68: S23–S36.
18.
PanchalAPerez-MarquesF.Intravenous immunoglobulin for acute hemorrhagic leukoencephalitis refractory to plasmapheresis. Clin Case Rep2019; 7: 160–163.
19.
AlawadhiASaint-MartinCBhanjiF, et al. Acute hemorrhagic encephalitis responding to combined decompressive craniectomy, intravenous immunoglobulin, and corticosteroid therapies: Association with Novel RANBP2 variant. Front Neurol2018; 9: 130.
20.
YoungNPWeinshenkerBGParisiJE, et al. Perivenous demyelination: Association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain2010; 133(Pt. 2): 333–348.
21.
TeaFLopezJARamanathanS, et al. Characterization of the human myelin oligodendrocyte glycoprotein antibody response in demyelination. Acta Neuropathol Commun2019; 7: 145.
22.
StimmerLFovetCMSergueraC.Experimental models of autoimmune demyelinating diseases in nonhuman primates. Vet Pathol2018; 55(1): 27–41.
23.
HoftbergerRGuoYFlanaganEP, et al. The pathology of central nervous system inflammatory demyelinating disease accompanying myelin oligodendrocyte glycoprotein autoantibody. Acta Neuropathol2020; 139: 875–892.
24.
ColeJEvansEMwangiM, et al. Acute disseminated encephalomyelitis in children: An updated review based on current diagnostic criteria. Pediatr Neurol2019; 100: 26–34.
25.
HennesEMBaumannMSchandaK, et al. Prognostic relevance of MOG antibodies in children with an acquired demyelinating syndrome. Neurology2017; 89: 900–908.
26.
DuignanSWrightSRossorT, et al. Myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies are highly specific in children with acquired demyelinating syndromes. Dev Med Child Neurol2018; 60(9): 958–962.
27.
PohlDAlperGVan HarenK, et al. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology2016; 87: S38–S45.
28.
SerraMPresicciAFucciM, et al. Acute disseminated encephalomyelitis followed by optic neuritis: A rare syndrome of uncertain treatment and prognosis. Neuropediatrics. Epub ahead of print 14January2020. DOI: 10.1055/s-0039-3402004.
29.
HuppkePRostasyKKarenfortM, et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler2013; 19: 941–946.
30.
MariottoSGajofattoABatzuL, et al. Relevance of antibodies to myelin oligodendrocyte glycoprotein in CSF of seronegative cases. Neurology2019; 93: e1867–e1872.
31.
Cobo-CalvoARuizAMaillartE, et al. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study. Neurology2018; 90: e1858–e1869.
32.
MiyaueNYamanishiYTadaS, et al. A case of ADEM-like presentation with anti-MOG antibody following tumefactive demyelinating lesion. Mult Scler Relat Disord2019; 31: 62–64.
33.
Lopez-ChiribogaASMajedMFryerJ, et al. Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol2018; 75: 1355–1363.
34.
SalamaSKhanMPardoS, et al. MOG antibody-associated encephalomyelitis/encephalitis. Mult Scler2019; 25(11): 1427–1433.
35.
HacohenYRossorTMankadK, et al. “Leukodystrophy-like” phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease. Dev Med Child Neurol2018; 60(4): 417–423.
36.
ArmangueTOlivé-CireraGMartínez-HernandezE, et al. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: A multicentre observational study. Lancet Neurol2020; 19: 234–246.
37.
WatersPFaddaGWoodhallM, et al. Serial anti-myelin oligodendrocyte glycoprotein antibody analyses and outcomes in children with demyelinating syndromes. JAMA Neurol2019; 77: 2940.
38.
FlanaganEPHinsonSRLennonVA, et al. Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Ann Neurol2017; 81(2): 298–309.
39.
WaldmanATGormanMPRenselMR, et al. Management of pediatric central nervous system demyelinating disorders: Consensus of United States neurologists. J Child Neurol2011; 26(6): 675–682.
40.
GadianJKirkEHollidayK, et al. Systematic review of immunoglobulin use in paediatric neurological and neurodevelopmental disorders. Dev Med Child Neurol2017; 59(2): 136–144.
41.
PressCAKirschenMLaRovereK, et al. Variation in treatment and outcomes of children with acute disseminated encephalomyelitis. Hosp Pediatr2020; 10(2): 159–165.
Hino-FukuyoNHaginoyaKTakahashiT, et al. Long-term outcome of a group of Japanese children with myelin-oligodendrocyte glycoprotein encephalomyelitis without preventive immunosuppressive therapy. Brain Dev2019; 41(9): 790–795.
44.
HacohenYWongYYLechnerC, et al. Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease. JAMA Neurol2018; 75: 478–487.
45.
RamanathanSMohammadSTantsisE, et al. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry2018; 89(2): 127–137.
46.
WinterMBaksmeierCSteckelJ, et al. Dose-dependent inhibition of demyelination and microglia activation by IVIG. Ann Clin Transl Neurol2016; 3: 828–843.
47.
AbsoudMParslowRCWassmerE, et al. Severe acute disseminated encephalomyelitis paediatric intensive care population-based study. Mult Scler2011; 17(10): 1258–1261.
48.
Aubert-BrocheBWeierKLongoniG, et al. Monophasic demyelination reduces brain growth in children. Neurology2017; 88: 1744–1750.
49.
JacobsRKAndersonVANealeJL, et al. Neuropsychological outcome after acute disseminated encephalomyelitis: Impact of age at illness onset. Pediatr Neurol2004; 31(3): 191–197.
50.
SuppiejACainelliECasaraG, et al. Long-term neurocognitive outcome and quality of life in pediatric acute disseminated encephalomyelitis. Pediatr Neurol2014; 50(4): 363–367.
