title: Acute disseminated encephalomyelitis in 228 patients: A retrospective, multicenter US study.
abstract: OBJECTIVE
  To analyze the range of demographic, clinical, MRI, and CSF features of acute disseminated encephalomyelitis (ADEM), a rare, typically monophasic demyelinating disorder, and analyze long-term outcomes including time and risk factors for subsequent clinical events as well as competing diagnoses.
  
  
  METHODS
  We performed a retrospective, multicenter study in 4 US academic medical centers of all patients clinically diagnosed with ADEM. Initial presentation of pediatric and adult ADEM and monophasic and multiphasic disease were compared. The Aalen-Johansen estimator was used to produce estimates of the probability of transitioning to a multiphasic diagnosis as a function of time since initial diagnosis, treating death and alternative diagnoses as competing risks.
  
  
  RESULTS
  Of 228 patients (122 children, age range 1-72 years, 106 male, median follow-up 24 months [25th-75th percentile 6-67], 7 deaths), approximately one quarter (n = 55, 24%) experienced at least one relapse. Relapsing disease in children was more often diagnosed as multiphasic ADEM than in adults (58% vs 21%, p = 0.007), in whom MS was diagnosed more often. Encephalopathy at initial presentation (hazard ratio [HR] 0.383, p = 0.001), male sex (HR 0.394, p = 0.002), and increasing age at onset (HR 0.984, p = 0.035) were independently associated with a longer time to a demyelinating disease relapse in a multivariable model. In 17 patients, diagnoses other than demyelinating disease were concluded in long-term follow-up.
  
  
  CONCLUSIONS
  Relapsing disease after ADEM is fairly common and associated with a few potentially predictive features at initial presentation. Age-specific guidelines for ADEM diagnosis and treatment may be valuable, and vigilance for other, mostly rare, diseases is imperative.
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Diederik L H
authors.initials: DL
authors.lastname: Koelman
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Salim
authors.initials: S
authors.lastname: Chahin
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Soe S
authors.initials: SS
authors.lastname: Mar
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Arun
authors.initials: A
authors.lastname: Venkatesan
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: George M
authors.initials: GM
authors.lastname: Hoganson
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Anusha K
authors.initials: AK
authors.lastname: Yeshokumar
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Paula
authors.initials: P
authors.lastname: Barreras
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Bittu
authors.initials: B
authors.lastname: Majmudar
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Klein
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: David C
authors.initials: DC
authors.lastname: Benkeser
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle.
authors.forename: Marco
authors.initials: M
authors.lastname: Carone
authors.affiliation: From the Department of Neurology (D.L.H.K., T.C., F.J.M.), Massachusetts General Hospital, Boston; Department of Neurology (D.L.H.K.), Academic Medical Center, Amsterdam, the Netherlands; Department of Neurology (S.C.), University of Pennsylvania, Philadelphia; Department of Neurology (S.S.M., G.M.H., B.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (A.V., A.K.Y., P.B.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (J.P.K.), Brigham and Women's Hospital, Boston; Harvard Medical School (J.P.K., F.J.M.), Boston, MA; and Department of Biostatistics (D.C.B., M.C.), University of Washington, Seattle. fmateen@partners.org.
authors.forename: Farrah J
authors.initials: FJ
authors.lastname: Mateen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D004673:Encephalomyelitis, Acute Disseminated / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult