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Prognostic factors for functional recovery in children with moderate to severe acute disseminated encephalomyelitis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Li-Wen Chen
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Pediatrics, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, North District, Tainan, Taiwan
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Ju-Fang Cheng
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Pediatrics, Changhua Christian Children's Hospital, 320 Xuguang Road, Changhua City, Changhua County, Taiwan
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  • Tung-Ming Chang
    Affiliations
    Department of Pediatrics, Changhua Christian Children's Hospital, 320 Xuguang Road, Changhua City, Changhua County, Taiwan

    Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, 1001 Daxue Road, East District, Hsinchu, Taiwan
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  • Mei-Hsin Hsu
    Affiliations
    Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Road, Niaosong District, Kaohsiung City 833, Taiwan
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  • Chao-Ching Huang
    Affiliations
    Department of Pediatrics, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, 138 Sheng-Li Road, North District, Tainan, Taiwan

    Department of Pediatrics, College of Medicine, Taipei Medical University, 50 Wu-Hsing Street, Taipei, Taiwan
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  • Ying-Chao Chang
    Correspondence
    Corresponding author.
    Affiliations
    Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 123 Dapi Road, Niaosong District, Kaohsiung City 833, Taiwan
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  • Author Footnotes
    1 These authors contributed equally to this work.

      Highlights

      • Nearly 1/4 of children with moderate to severe ADEM had poor functional recoveries.
      • Prodromal headache was an indicator for good outcomes.
      • Dystonia, myoclonus, and cerebellar lesions on MRI suggested poor recoveries.
      • Immunotherapies may be adjusted in children prone to poor functional recoveries.

      Abstract

      Background

      Acute disseminated encephalomyelitis (ADEM) is an immune-mediated encephalopathy with heterogeneous disease courses. However, clinical characteristics for a prognostication of functional recovery from acute episodes of ADEM remain limited. The study aims to characterize the clinical presentations and neuroimaging findings of children with poor functional recoveries from acute episodes of moderate to severe ADEM.

      Methods

      The multicenter retrospective cohort study included children under 18 years of age who presented with moderate to severe ADEM (modified Rankin Scale [mRS] ≥ 3 at nadir) from 2002 to 2019. Children were assigned to a good recovery group (mRS ≤ 2) and a poor recovery group (mRS ≥ 3) after mean 4.3 months of follow-up. The clinical presentations and the distribution of brain lesions on magnetic resonance imaging were compared between the two groups by the t-test for numerical variables and Fisher's exact test for categorical variables. Analyses of logistic regression were conducted and significant variables in the multivariate model were examined by the receiver operating characteristic curve for the prediction of functional recovery.

      Results

      Among the 73 children with moderate to severe ADEM, 56 (77%) had good functional recoveries and 17 (23%) showed poor functional recoveries. Children with poor recoveries had a lower rate of prodromal headache (12% vs. 39%, p = 0.04), and presented with higher proportions of dystonia (29% vs. 9%, p = 0.046), myoclonus (24% vs. 2%, p = 0.009), and cerebellar lesions on neuroimages (59% vs. 23%, p = 0.01). The multivariate analyses identified that a lack of prodromal headache (OR 0.1, 95% CI 0.005 - 0.7, p = 0.06) and the presentations of myoclonus (OR 21.6, 95% CI 1.7 – 874, p = 0.04) and cerebellar lesions (OR 4.8, 95% CI 1.3 - 19.9, p = 0.02) were associated with poor functional recoveries. These three factors could prognosticate poor outcomes in children with moderate to severe ADEM (area under the receiver operating characteristic curve 0.80, 95% CI 0.68 – 0.93, p = 0.0002).

      Conclusion

      Nearly one-fourth of children with moderate to severe ADEM had a poor functional recovery from acute episodes, who were characterized by a lack of prodromal headache, the presentation of myoclonus, and the neuroimaging finding of cerebellar lesions. The clinical variables associated with poor functional recoveries could assist in the planning of immunotherapies during hospitalization for a better outcome in moderate to severe ADEM.

      Keywords

      Abbreviations:

      ADEM (acute demyelinating encephalomyelitis), MOG (myelin oligodendrocyte glycoprotein), mRS (modified rankin scale), NMDAR (N-methyl-D-aspartate receptor)
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