Acute Disseminated Encephalomyelitis Treatment & Management
- Author: J Nicholas Brenton, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS more...
Acute disseminated encephalomyelitis (ADEM) is often treated with high-dose intravenous corticosteroids, to which it appears to be responsive. One common protocol is 20-30 mg/kg/d of methylprednisolone (maximum dose of 1 g/d) for 3-5 days. Improvement may be observed within hours but usually requires several days. An oral taper for 4-6 weeks or some other interval is sometimes appended.
Though there is conflicting data, at least two studies have presented data suggesting that steroid taper of 3 weeks or less may increase the risk of relapse in ADEM. [47, 63]
Taper-related recurrence occurs in as many as 3-5% of cases and usually responds to prolongation of taper. Similar phenomena occur in other postinfectious diseases, such as Guillain-Barré syndrome or opsoclonus-myoclonus. A subset of patients manifest repeated recurrences that prevent discontinuation of corticosteroids or necessitate changing to various steroid-sparing treatments such as cyclophosphamide or beta-interferons. This rare and interesting subgroup tends to have onset of disease before 6 years of age, and despite recurrence, these children do not manifest evidence for CSF immune profile (ie, IgG index, IgG synthetic rate, oligoclonal bands) abnormality. The relationship of this group to patients with ADEM or MS or some other form of inflammatory CNS illness remains unclear.
The chief alternative therapy is intravenous immune globulin (IVIG).[18, 86] It is administered as 2 g/kg intravenously as a single dose or over the course of 3-5 days. IVIG may be preferable in instances where meningo-encephalitis cannot be excluded based upon the hypothesis that corticosteroids might worsen the course of infection.
Available published information concerning efficacy is inadequate to accurately assess much concerning the impact of either form of therapy, although it appears likely that both forms of therapy increase the pace of initial recovery. Whether these forms of therapy influence times to final outcome or extent of final recovery is not known.
Theoretically, very high-dose corticosteroids (30-50 mg/kg) administered intravenously at presentation to patients with transverse myelitis may be advantageous from the vantage point of its capacity to close the blood-brain barrier and limit swelling. Marked cord swelling may account for poor outcome in some cases of transverse myelitis because of circulatory impairment and cord infarction. The same argument may hold true for severe cerebral ADEM such as tends to arise in some young children (< 3 y old) who also may have marked permanent neurologic impairments after severe ADEM.
There is as yet no convincing evidence that treatment with the combination of intravenous corticosteroids and IVIG confers any advantage in such cases, although this approach is employed by some clinicians.
Severe ADEM has also been treated, apparently successfully, with such alternative approaches as (1) combination of intravenous corticosteroids and IVIG, (2) cyclosporin, (3) cyclophosphamide, or (4) plasma exchange/plasmapheresis.[19, 20, 87] Greater understanding of trimolecular complex regulation, adhesion molecules, and inflammatory cytokines may permit development of more specific and effective ADEM therapies. The polymorphism of the human major histocompatibility complex and apparent heterogeneity of T cell response to autoantigens render this a daunting project, although anti-cytokines represent an intriguing avenue of therapeutic research.
Surgical treatment for severely elevated intracranial pressure has been undertaken for cases of AHLE, hemorrhagic brain purpura, and non-Reye syndrome, examples of what have been termed obscure encephalopathies of infancy. Some of these cases were likely examples of hyperacute ADEM. Surgical interventions have ranged from placement of pressure bolts to decompression of the intracranial fossae by unroofing of the cranium. Outcome of such interventions was mixed.
Although such severe cases were regularly noted in the medical literature from the 1920s until the mid 1970s, few examples have been noted since that time. Prevalence clearly has dramatically decreased. Because these severe cases often followed measles, mumps, and other diseases for which effective vaccines have been developed and because the disappearance of such cases has followed the availability and use of such vaccines (earlier disappearance in the United States and Western Europe, subsequent disappearance in Asia and the Middle East), this change in prevalence likely reflects the removal of pathogens that are provocative of such severe forms of ADEM.
Consultations with infectious disease specialists are occasionally warranted to consider alternative diagnoses. Pediatric intensivists generally become involved in severe cases for management of airway, breathing, and circulation.
No clear restrictions on activity exist except as indicated by the severity of disease. The possible exceptions are ADEM-related postinfectious demyelinating syndromes, sometimes in association with the development of brain edema, that arise in the wake of illnesses such as brucellosis or malaria. In the case of acute brucellosis, recovery is clearly more rapid and relapse is less likely if patients are treated with enforced bedrest. This rule may also be true of the relapsing neurobrucellotic illnesses, including the types that closely resemble or are examples of ADEM. Although somewhat less clear in the case of cerebral malaria, little doubt exists that enforced bedrest with appropriate positioning (because of elevation of intracranial pressure) is of importance. In the case of cerebral malaria and in cases of the more severe varieties of neurobrucellosis, bedrest is often necessary because of the low mental status and weakness of such individuals.
Alper G. Acute disseminated encephalomyelitis. J Child Neurol. 2012 Nov. 27(11):1408-25. [Medline].
Huppke P, Rostasy K, Karenfort M, Huppke B, Seidl R, Leiz S, et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler. 2012 Nov 5. [Medline].
Ishizu T, Minohara M, Ichiyama T, et al. CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis. J Neuroimmunol. 2006 Jun. 175(1-2):52-8. [Medline].
Franciotta D, Zardini E, Ravaglia S, et al. Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis. J Neurol Sci. 2006 Sep 25. 247(2):202-7. [Medline].
Banwell B, Kennedy J, Sadovnick D, Arnold DL, Magalhaes S, Wambera K, et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology. 2009 Jan 20. 72(3):232-9. [Medline].
Sacconi S, Salviati L, Merelli E. Acute disseminated encephalomyelitis associated with hepatitis C virus infection. Arch Neurol. 2001 Oct. 58(10):1679-81. [Medline].
Alper G, Heyman R, Wang L. Multiple sclerosis and acute disseminated encephalomyelitis diagnosed in children after long-term follow-up: comparison of presenting features. Dev Med Child Neurol. 2009 Jun. 51(6):480-6. [Medline]. [Full Text].
Chowdhary J, Ashraf SM, Khajuria K. Measles with acute disseminated encephalomyelitis (ADEM). Indian Pediatr. 2009 Jan. 46(1):72-4. [Medline].
Alves-Leon SV, Veluttini-Pimentel ML, Gouveia ME, Malfetano FR, Gaspareto EL, Alvarenga MP, et al. Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study. Arq Neuropsiquiatr. 2009 Sep. 67(3A):643-51. [Medline].
Rust RS, Dodson WE, Trotter JL. Cerebrospinal fluid IgG in childhood: the establishment of reference values. Ann Neurol. 1988 Apr. 23(4):406-10. [Medline].
Callen DJ, Shroff MM, Branson HM, Li DK, Lotze T, Stephens D, et al. Role of MRI in the differentiation of ADEM from MS in children. Neurology. 2009 Mar 17. 72(11):968-73. [Medline].
Baum PA, Barkovich AJ, Koch TK, Berg BO. Deep gray matter involvement in children with acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 1994 Aug. 15(7):1275-83. [Medline].
Apak RA, Kose G, Anlar B, et al. Acute disseminated encephalomyelitis in childhood: report of 10 cases. J Child Neurol. 1999 Mar. 14(3):198-201. [Medline].
Kesselring J, Miller DH, Robb SA, Kendall BE, Moseley IF, Kingsley D, et al. Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain. 1990 Apr. 113 ( Pt 2):291-302. [Medline].
van der Meyden CH, de Villiers JF, Middlecote BD, Terblanchè J. Gadolinium ring enhancement and mass effect in acute disseminated encephalomyelitis. Neuroradiology. 1994 Apr. 36(3):221-3. [Medline].
Honkaniemi J, Dastidar P, Kähärä V, Haapasalo H. Delayed MR imaging changes in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 2001 Jun-Jul. 22(6):1117-24. [Medline].
Trotter JL, Rust RS. Human cerebrospinal fluid immunology. In: Herndon RM, Brumback RA, eds. The Cerebrospinal Fluid. Boston, Mass:. Kluwer Academic Publishers. 1989:179-226.
Nishikawa M, Ichiyama T, Hayashi T, Ouchi K, Furukawa S. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol. 1999 Aug. 21(2):583-6. [Medline].
Stricker RB, Miller RG, Kiprov DD. Role of plasmapheresis in acute disseminated (postinfectious) encephalomyelitis. J Clin Apher. 1992. 7(4):173-9. [Medline].
Kanter DS, Horensky D, Sperling RA, Kaplan JD, Malachowski ME, Churchill WH Jr. Plasmapheresis in fulminant acute disseminated encephalomyelitis. Neurology. 1995 Apr. 45(4):824-7. [Medline].
Sugita K, Suzuki N, Shimizu N, Takanashi J, Ishii M, Niimi N. Involvement of cytokines in N-methyl-N'-nitro-N-nitrosoguanidine-induced plasminogen activator activity in acute disseminated encephalomyelitis and multiple sclerosis lymphocytes. Eur Neurol. 1993. 33(5):358-62. [Medline].
Kuni BJ, Banwell BL, Till C. Cognitive and Behavioral Outcomes in Individuals With a History of Acute Disseminated Encephalomyelitis (ADEM). Dev Neuropsychol. 2012 Nov. 37(8):682-96. [Medline].
Atalar MH. Acute disseminated encephalomyelitis in an adult patient. Magnetic resonance and diffusion-weighted imaging findings. Saudi Med J. 2006 Jan. 27(1):105-8. [Medline].
Brinar VV. Non-MS recurrent demyelinating illnesses. Clin Neurol Neurosurg. 2004. 106(3):197-210.
Dale RC, Branson JA. Acute disseminated encephalomyelitis or multiple sclerosis: can the initial presentation help in establishing a correct diagnosis?. Arch Dis Child. 2005 Jun. 90(6):636-9. [Medline].
Garg RK. Acute disseminated encephalomyelitis. Postgrad Med J. 2003 Jan. 79(927):11-7. [Medline].
Hahn JS, Siegler DJ, Enzmann D. Intravenous gammaglobulin therapy in recurrent acute disseminated encephalomyelitis. Neurology. 1996 Apr. 46(4):1173-4. [Medline].
Hartel C, Schilling S, Gottschalk S, Sperner J. Multiphasic disseminated encephalomyelitis associated with streptococcal infection. Eur J Paediatr Neurol. 2002. 6(6):327-9. [Medline].
Holtmannspotter M, Inglese M, Rovaris M, et al. A diffusion tensor MRI study of basal ganglia from patients with ADEM. J Neurol Sci. 2003 Jan 15. 206(1):27-30. [Medline].
John L, Khaleeli AA, Larner AJ. Acute disseminated encephalomyelitis: a riddle wrapped in a mystery inside an enigma. Int J Clin Pract. 2003 Apr. 57(3):235-7. [Medline].
Kadhim H, De Prez C, Gazagnes MD, Sebire G. In situ cytokine immune responses in acute disseminated encephalomyelitis: insights into pathophysiologic mechanisms. Hum Pathol. 2003 Mar. 34(3):293-7. [Medline].
Mariotti P, Batocchi AP, Colosimo C,et al. Multiphasic demyelinating disease involving central and peripheral nervous system in a child. Neurology. 2003 Jan 28. 60(2):348-9. [Medline].
Murthy JM. Acute disseminated encephalomyelitis. Neurol India. 2002 Sep. 50(3):238-43. [Medline].
Oksuzler YF, Cakmakci H, Kurul S, et al. Diagnostic value of diffusion-weighted magnetic resonance imaging in pediatric cerebral diseases. Pediatr Neurol. 2005 May. 32(5):325-33. [Medline].
Pena JA, Montiel-Nava C, Hernandez F, et al. [Disseminated acute encephalomyelitis in children]. Rev Neurol. 2002 Jan 16-31. 34(2):163-8. [Medline].
Pradhan S, Gupta RP, Shashank S, Pandey N. Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. J Neurol Sci. 1999 May 1. 165(1):56-61. [Medline].
Rust RS. Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions. Semin Pediatr Neurol. 2000 Jun. 7(2):66-90. [Medline].
Sakakibara R, Yamanishi T, Uchiyama T, Hattori T. Acute urinary retention due to benign inflammatory nervous diseases. J Neurol. 2006 Aug. 253(8):1103-10. [Medline].
Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B. Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology. 2001 May 22. 56(10):1313-8. [Medline].
Sunnerhagen KS, Johansson K, Ekholm S. Rehabilitation problems after acute disseminated encephalomyelitis: four cases. J Rehabil Med. 2003 Jan. 35(1):20-5. [Medline].
Tenembaum S, Chamoles N. Acute disseminated encephalomyelitis: a longterm follow-up study of 84 pediatric patients. J Neurol Neurosurg Psychiatr. 1995. 58(4):467-470.
Verbruggen SC, Catsman CE, Naghib S, et al. [Respiratory insufficiency caused by acute disseminated encephalomyelitis in a child]. Ned Tijdschr Geneeskd. 2006 May 20. 150(20):1134-8. [Medline].
Weng WC, Peng SS, Lee WT, et al. Acute disseminated encephalomyelitis in children: one medical center experience. Acta Paediatr Taiwan. 2006 Mar-Apr. 47(2):67-71. [Medline].
Wingerchuk DM. The clinical course of acute disseminated encephalomyelitis. Neurol Res. 2006 Apr. 28(3):341-7. [Medline].
Yapici Z, Eraksoy M. Bilateral demyelinating tumefactive lesions in three children with hemiparesis. J Child Neurol. 2002 Sep. 17(9):655-60. [Medline].
Tenembaum S, Chitnis T, Ness J, Hahn JS. Acute disseminated encephalomyelitis. Neurology. 2007. 68(suppl 2):S23-S36. [Full Text].
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 Dec. 123 Pt 12:2407-22. [Medline].
Dale RC. Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 2003 Apr. 14(2):90-5. [Medline].
Van Haren K, Tomooka BH, Kidd BA, Banwell B, Bar-Or A, Chitnis T. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis. Mult Scler. 2013 Nov. 19(13):1726-33. [Medline].
Baumann M, Sahin K, Lechner C, Hennes EM, Schanda K, Mader S. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry. 2014 Aug 13. [Medline].
Pröbstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology. 2011 Aug 9. 77(6):580-8. [Medline].
Brilot F, Dale RC, Selter RC, Grummel V, Kalluri SR, Aslam M, et al. Antibodies to native myelin oligodendrocyte glycoprotein in children with inflammatory demyelinating central nervous system disease. Ann Neurol. 2009 Dec. 66(6):833-42. [Medline].
Di Pauli F, Mader S, Rostasy K, Schanda K, Bajer-Kornek B, Ehling R. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases. Clin Immunol. 2011 Mar. 138(3):247-54. [Medline].
Murthy SN, Faden HS, Cohen ME, Bakshi R. Acute disseminated encephalomyelitis in children. Pediatrics. 2002 Aug. 110(2 Pt 1):e21. [Medline].
Leake JA, Albani S, Kao AS, Senac MO, Billman GF, Nespeca MP, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J. 2004 Aug. 23(8):756-64. [Medline].
Pohl D, Hennemuth I, von Kries R, Hanefeld F. Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr. 2007 May. 166(5):405-12. [Medline].
Torisu H, Kira R, Ishizaki Y, Sanefuji M, Yamaguchi Y, Yasumoto S. Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan. Brain Dev. 2010 Jun. 32(6):454-62. [Medline].
Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean MJ. Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology. 2001 May 22. 56(10):1308-12. [Medline].
Krupp LB, Tardieu M, Amato MP, Banwell B, Chitnis T, Dale RC, 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 Scler. 2013 Sep. 19(10):1261-7. [Medline].
Hung KL, Liao HT, Tsai ML. The spectrum of postinfectious encephalomyelitis. Brain Dev. 2001 Mar. 23(1):42-5. [Medline].
Mikaeloff Y, Suissa S, Vallée L, Lubetzki C, Ponsot G, Confavreux C, et al. First episode of acute CNS inflammatory demyelination in childhood: prognostic factors for multiple sclerosis and disability. J Pediatr. 2004 Feb. 144(2):246-52. [Medline].
Idrissova ZhR, Boldyreva MN, Dekonenko EP, Malishev NA, Leontyeva IY, Martinenko IN, et al. Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol. 2003 Sep. 10(5):537-46. [Medline].
Anlar B, Basaran C, Kose G, Guven A, Haspolat S, Yakut A, et al. Acute disseminated encephalomyelitis in children: outcome and prognosis. Neuropediatrics. 2003 Aug. 34(4):194-9. [Medline].
Jacobs RK, Anderson VA, Neale JL, Shield LK, Kornberg AJ. Neuropsychological outcome after acute disseminated encephalomyelitis: impact of age at illness onset. Pediatr Neurol. 2004 Sep. 31(3):191-7. [Medline].
Hahn CD, Miles BS, MacGregor DL, Blaser SI, Banwell BL, Hetherington CR. Neurocognitive outcome after acute disseminated encephalomyelitis. Pediatr Neurol. 2003 Aug. 29(2):117-23. [Medline].
Brenton JN, Koenig S, Goldman MD. Vitamin D status and age of onset of demyelinating disease. Multiple Sclerosis and Related Disorders. 2014. [Full Text].
Mowry EM, James JA, Krupp LB, Waubant E. Vitamin D status and antibody levels to common viruses in pediatric-onset multiple sclerosis. Mult Scler. 2011 Jun. 17(6):666-71. [Medline].
Banwell B, Bar-Or A, Arnold DL, Sadovnick D, Narayanan S, McGowan M. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol. 2011 May. 10(5):436-45. [Medline].
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20. 296(23):2832-8. [Medline].
Mikaeloff Y, Caridade G, Husson B, Suissa S, Tardieu M. Acute disseminated encephalomyelitis cohort study: prognostic factors for relapse. Eur J Paediatr Neurol. 2007 Mar. 11(2):90-5. [Medline].
McKeon A, Lennon VA, Lotze T, Tenenbaum S, Ness JM, Rensel M, et al. CNS aquaporin-4 autoimmunity in children. Neurology. 2008 Jul 8. 71(2):93-100. [Medline].
Saiki S, Ueno Y, Moritani T, Sato T, Sekine T, Kawajiri S. Extensive hemispheric lesions with radiological evidence of blood-brain barrier integrity in a patient with neuromyelitis optica. J Neurol Sci. 2009 Sep 15. 284(1-2):217-9. [Medline].
Eichel R, Meiner Z, Abramsky O, Gotkine M. Acute disseminating encephalomyelitis in neuromyelitis optica: closing the floodgates. Arch Neurol. 2008 Feb. 65(2):267-71. [Medline].
Kaneko K, Sato DK, Misu T, Kurosawa K, Nakashima I, Fujihara K. Anti-N-methyl-D-aspartate receptor encephalitis with multiphasic demyelination. Ann Neurol. 2014 Sep. 76(3):462-4. [Medline].
Okumura A, Nakazawa M, Igarashi A, Abe S, Ikeno M, Nakahara E, et al. Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis. Brain Dev. 2014 May 16. [Medline].
Titulaer MJ, Höftberger R, Iizuka T, Leypoldt F, McCracken L, Cellucci T, et al. Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2014 Mar. 75(3):411-28. [Medline]. [Full Text].
Huppke P, Rostasy K, Karenfort M, Huppke B, Seidl R, Leiz S, et al. Acute disseminated encephalomyelitis followed by recurrent or monophasic optic neuritis in pediatric patients. Mult Scler. 2013 Jun. 19(7):941-6. [Medline].
Shaw CM, Alvord EC Jr. Multiple sclerosis beginning in infancy. J Child Neurol. 1987 Oct. 2(4):252-6. [Medline].
Maeda Y, Kitamoto I, Kurokawa T, Ueda K, Hasuo K, Fujioka K. Infantile multiple sclerosis with extensive white matter lesions. Pediatr Neurol. 1989 Sep-Oct. 5(5):317-9. [Medline].
Vliegenthart WE, Sanders EA, Bruyn GW, Vielvoye GJ. An unusual CT-scan appearance in multiple sclerosis. J Neurol Sci. 1985 Nov. 71(1):129-34. [Medline].
Noorbakhsh F, Johnson RT, Emery D, Power C. Acute disseminated encephalomyelitis: clinical and pathogenesis features. Neurol Clin. 2008 Aug. 26(3):759-80, ix. [Medline].
Cohen SR, Brooks BR, Herndon RM, McKhann GM. A diagnostic index of active demyelination: myelin basic protein in cerebrospinal fluid. Ann Neurol. 1980 Jul. 8(1):25-31. [Medline].
Höllinger P, Sturzenegger M, Mathis J, Schroth G, Hess CW. Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF, EEG, and MRI findings. J Neurol. 2002 Mar. 249(3):320-9. [Medline].
Tenembaum S, Chamoles N, Fejerman N. Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology. 2002 Oct 22. 59(8):1224-31. [Medline].
Kleiman M, Brunquell P. Acute disseminated encephalomyelitis: response to intravenous immunoglobulin. J Child Neurol. 1995 Nov. 10(6):481-3. [Medline].
Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology. 2002 Jan 8. 58(1):143-6. [Medline].
Rust RS, Mathisen J, Prensky AL, et al. Acute disseminatedencephalomyelitis (ADE) and childhood multiple sclerosis(MS). Ann Neurol. 1989. 26:467.