Treatment and outcome of aquaporin-4 antibody-positive NMOSD: A multinational pediatric study

Renata Barbosa Paolilo, Yael Hacohen, Elise Yazbeck, Thais Armangue, Arlette Bruijstens, Christian Lechner, Samira Luisa Apostolos-Pereira, Yana Martynenko, Markus Breu, Carolina de Medeiros Rimkus, Evangeline Wassmer, Matthias Baumann, Laura Papetti, Marco Capobianco, Barbara Kornek, Kevin Rostásy, José Albino da Paz, Olga Ciccarelli, Ming Lim, Albert SaizRinze Neuteboom, Romain Marignier, Cheryl Hemingway, Douglas Kazutoshi Sato, Kumaran Deiva

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: To describe the clinical phenotypes, treatment response, and outcome of children with antibodies against aquaporin-4 (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD). METHODS: Retrospective, multicenter, and multinational study of patients with AQP4-Ab NMOSD aged <18 years at disease onset from a center in Brazil and 13 European centers. Data on demographics, clinical findings, and laboratory results were analyzed; calculation of annualized relapse rates (ARRs) pre- and on-treatment with disease-modifying therapies (DMTs) and of ORs for predictors of poor outcome was performed. RESULTS: A total of 67 children were identified. At last follow-up (median 4 years, interquartile range 2-10 years), 37/67(57.8%) were found to have permanent disability. A more severe disease course was seen in the non-White ethnicity with both a shorter time to first relapse (p = 0.049) and a worse Expanded Disability Status Scale score at last follow-up (p = 0.008). The median ARR on treatment was 0.18 on azathioprine (n = 39, range 0-4), 0 on mycophenolate mofetil (n = 18, range 0-3), and 0 on rituximab (n = 29, range 0-2). No patient treated with rituximab as first-line therapy relapsed. Optic neuritis at onset was associated with a poor visual outcome below 20/200 (OR 8.669, 95% CI 1.764-42.616, p = 0.008), and a younger age at onset was associated with cognitive impairment (OR 0.786, 95% CI 0.644-0.959, p = 0.018). CONCLUSIONS: AQP4-Ab NMOSD in children is an aggressive disease with permanent disabilities observed in over half the cohort. All DMTs were associated with a reduction of ARR. First-line rituximab prevented further clinical relapses. International consensus on treatment protocols for children is required to reduce heterogeneity of treatment regimens used worldwide. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with AQP4-Ab NMOSD, all DMTs, particularly first-line rituximab, reduced the ARR and prevented further clinical relapses.

Original languageEnglish
JournalNeurology(R) neuroimmunology & neuroinflammation
Issue number5
Publication statusPublished - Sep 1 2020

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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