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Early predictors of disability of paediatric-onset AQP4-IgG-seropositive neuromyelitis optica spectrum disorders
  1. Valentina Camera1,2,3,
  2. Silvia Messina1,3,
  3. Kariem Tarek Elhadd4,
  4. Julia Sanpera-Iglesias5,
  5. Romina Mariano1,3,
  6. Yael Hacohen6,7,
  7. Ruth Dobson8,
  8. Stefano Meletti2,9,
  9. Evangeline Wassmer10,
  10. Ming J Lim5,11,
  11. Saif Huda4,
  12. Cheryl Hemingway7,
  13. Maria Isabel Leite1,3,
  14. Sithara Ramdas12,13,
  15. Jacqueline Palace1,3
  1. 1 Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK
  2. 2 Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy
  3. 3 Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK
  4. 4 The Walton Centre for Neurology and Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK
  5. 5 Children’s Neurosciences, Evelina London Children's Hospital, London, UK
  6. 6 Department of Neuroinflammation, Queen Square MS Centre, University College London, London, UK
  7. 7 Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, UK
  8. 8 Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
  9. 9 Neurology Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
  10. 10 Department of Paediatric Neurology, Birmingham Women’s and Children’s Hospitals NHS Foundation Trust, Birmingham, UK
  11. 11 Department of Women and Children’s Health, King's College London, London, UK
  12. 12 Department of Paediatric Neurology, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK
  13. 13 Department of Paediatrics, University of Oxford, Oxford, UK
  1. Correspondence to Dr Jacqueline Palace, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; jacqueline.palace{at}


Objective To describe onset clinical features predicting time to first relapse and time to long-term visual, motor and cognitive disabilities in paediatric-onset aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSDs).

Methods In this retrospective UK multicentre cohort study, we recorded clinical data of paediatric-onset AQP4-IgG NMOSD. Univariate and exploratory multivariable Cox proportional hazard models were used to identify long-term predictors of permanent visual disability, Expanded Disability Status Scale (EDSS) score of 4 and cognitive impairment.

Results We included 49 paediatric-onset AQP4-IgG patients (38.8% white, 34.7% black, 20.4% Asians and 6.1% mixed), mean onset age of 12±4.1 years, and 87.7% were female. Multifocal onset presentation occurred in 26.5% of patients, and optic nerve (47%), area postrema/brainstem (48.9%) and encephalon (28.6%) were the most involved areas. Overall, 52.3% of children had their first relapse within 1 year from disease onset. Children with onset age <12 years were more likely to have an earlier first relapse (p=0.030), despite showing no difference in time to immunosuppression compared with those aged 12–18 years at onset. At the cohort median disease duration of 79 months, 34.3% had developed permanent visual disability, 20.7% EDSS score 4 and 25.8% cognitive impairment. Visual disability was associated with white race (p=0.032) and optic neuritis presentations (p=0.002). Cognitive impairment was predicted by cerebral syndrome presentations (p=0.048), particularly if resistant to steroids (p=0.034).

Conclusions Age at onset, race, onset symptoms and resistance to acute therapy at onset attack predict first relapse and long-term disabilities. The recognition of these predictors may help to power future paediatric clinical trials and to direct early therapeutic decisions in AQP4-IgG NMOSD.

  • paediatric neurology

Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors VC, SMes, SMel, MJL, CH, SH, SR and JP: conception and design of the work; VC, SMes, KTE, JS-I, RM, YH, RD, EW, MIL and SR: acquisition and analysis of data for the work; VC, SMes, KTE, JS-I, RM, YH, RD, EW, SMel, MJL, CH, SH, MIL, SR and JP: drafting the work or revising it critically for important intellectual content and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding European Charcot Foundation research fellowship funded Dr. Valentina Camera. No award/grant number.

  • Competing interests VC reports funding from the European Charcot Foundation supporting for the present manuscript. No award/grant number. SM reports grants from Biogen, Novartis, Bayer, Merck, Almirall and Roche; RD reports grants from Barts Charity, MS Society of Great Britain, Horne Family Charitable Trust and Celgene; grants and consulting fees from Merck and Biogen, consulting fees from Roche, Teva, Sanofi Genzyne and Janssen; MJL reports consulting fees from Advisory Board Octapharma and from Advisory Board Novartis; non-financial support from Advisory Board CSL Behring; grants from NIHR, GOSH Charity and Action Medical Research; CH reports consulting fees from Novartis, Biogen, UCB and Roche; JP reports grants and consulting fees from Merck Serono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering; grants from MS Society and Guthie Jackson Foundation; payment for expert testimony and support for attending meetings and/or travel from Chugai Pharma and Bayer Schering, Alexion, Genzyme, MedImmune, EuroImmun, MedDay and ARGENX.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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