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The clinical profile of NMOSD in Australia and New Zealand

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Abstract

Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.

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Funding

Funding for this project was provided by Multiple Sclerosis Research Australia (Project Grant 11-038), Brain Foundation, Griffith Univerrsity/Gold Coast Hospital Foundation, Contributing to Australian Scholarship and Science, and NHS National Specialised Commissioning Group for NMO, NIHR Oxford Biomedical Research centre.

Author information

Author notes

  1. Wajih Bukhari and Laura Clarke are considered as co-first authors.

Authors and Affiliations

  1. Menzies Health Institute Queensland, School of Medicine, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia

    Wajih Bukhari, Laura Clarke, Cullen O’Gorman, Elham Khalilidehkordi, Simon Arnett, Sandeep Bhuta, Saman Heshmat, Sofia Jimenez-Sanchez & Simon A. Broadley

  2. Department of Neurology, Princess Alexandra Hospital, Wooloongabba, QLD, 4102, Australia

    Laura Clarke, Cullen O’Gorman & Robert J. Wilson

  3. Department of Neurology, Gold Coast University Hospital, Southport, QLD, 4215, Australia

    Elham Khalilidehkordi, Simon Arnett & Simon A. Broadley

  4. Department of Immunology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, 4006, Australia

    Kerri M. Prain, Angela Vincent & Patrick Waters

  5. Nuffield Department of Clinical Neurosciences, John Radcliffe Infirmary, University of Oxford, Oxford, OX3 9DU, UK

    Mark Woodhall

  6. Department of Immunopathology, Westmead Hospital, Westmead, NSW, 2145, Australia

    Roger Silvestrini

  7. School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, 6009, Australia

    Christine S. Bundell & Fabienne Brilot

  8. Brain Autoimmunity Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital, Westmead, NSW, 2145, Australia

    Sudarshini Ramanathan

  9. Department of Neurology, Wellington Hospital, Newtown, 6021, New Zealand

    David Abernethy & Michael Walsh

  10. Department of Neurology, Princess Alexandra Hospital, Woolloongabba, QLD, 4102, Australia

    Stefan Blum

  11. Department of Neurology, Townsville Hospital, Douglas, QLD, 4814, Australia

    Mike Boggild & Chris Kneebone

  12. Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia

    Karyn Boundy

  13. Centre for Applied Medical Research, St Vincent’s Hospital, University of New South Wales, Darlinghurst, NSW, 2010, Australia

    Bruce J. Brew

  14. Department of Neurology, Auckland City Hospital, Grafton, 1023, New Zealand

    Wallace Brownlee & Ernest Willoughby

  15. Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3010, Australia

    Helmut Butzkueven & Mark P. Marriott

  16. Centre for Neuromuscular and Neurological Disorders, Queen Elizabeth II Medical Centre, University of Western Australia, Nedlands, WA, 6009, Australia

    William M. Carroll & Allan G. Kermode

  17. Flinders Medical Centre, Flinders University, Bedford Park, SA, 5042, Australia

    Celia Chen & Mark Slee

  18. School of Medicine, Royal Brisbane and Women’s Hospital, University of Queensland, Herston, QLD, 4029, Australia

    Alan Coulthard, David Gillis & Richard C. Wong

  19. The Children’s Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, 2145, Australia

    Russell C. Dale, Robert Heard & Steve Vucic

  20. Department of Neurology, Canberra Hospital, Garran, ACT, 2605, Australia

    Chandi Das

  21. Global Health Research Centre, Duke Kunshan University, Kunshan, Jiangsu, China

    Keith Dear

  22. Western Australian Neuroscience Research Institute, Queen Elizabeth II Medical Centre, University of Western Australia, Nedlands, WA, 6009, Australia

    Marzena J. Fabis-Pedrini

  23. Sydney Medical School, Royal Prince Alfred Hospital, University of Sydney, Camperdown, NSW, 2006, Australia

    David Fulcher, Simon Hawke, Ming-Wei Lin, John D. Pollard, Judith Spies & John Parratt

  24. Department of Neurology, Westmead Hospital, Westmead, NSW, 2145, Australia

    Andrew P. D. Henderson

  25. South Western Sydney Medical School, Liverpool Hospital, University of New South Wales, Liverpool, NSW, 2170, Australia

    Suzanne Hodgkinson

  26. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3010, Australia

    Trevor J. Kilpatrick

  27. Department of Neurology, Royal Melbourne Hospital, Parkville, VIC, 3010, Australia

    John King

  28. School of Paediatrics, Royal Children’s Hospital, University of Melbourne, Parkville, VIC, 3010, Australia

    Andrew J. Kornberg & Eppie M. Yiu

  29. Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, 2305, Australia

    Jeannette Lechner-Scott

  30. School of Medicine, University of Auckland, Grafton, 1142, New Zealand

    Christopher Lynch & Jennifer Pereira

  31. Department of Neurology, Austin Health, Heidelberg, VIC, 3084, Australia

    Richard A. L. Macdonnell

  32. Department of Neurology, Christchurch Hospital, Christchurch, 8140, New Zealand

    Deborah F. Mason

  33. Centre for Clinical Research, Royal Brisbane and Women’s Hospital, University of Queensland, Herston, QLD, 4029, Australia

    Pamela A. McCombe

  34. Brain and Mind Research Institute, University of Sydney, Camperdown, NSW, 2006, Australia

    Stephen W. Reddel & Michael H. Barnett

  35. School of Medicine, Deakin University, Waurn Ponds, VIC, 3217, Australia

    Cameron Shaw & Bruce V. Taylor

  36. Menzies Research Institute, University of Tasmania, Hobart, TAS, 7000, Australia

    James Stankovich

  37. Department of Neurology, St Vincent’s Hospital, Darlinghurst, NSW, 2010, Australia

    Ian Sutton

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  1. Wajih Bukhari
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  2. Laura Clarke
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  3. Cullen O’Gorman
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  4. Elham Khalilidehkordi
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  5. Simon Arnett
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  6. Kerri M. Prain
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  7. Mark Woodhall
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  8. Roger Silvestrini
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  9. Christine S. Bundell
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  10. Sudarshini Ramanathan
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  11. David Abernethy
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  12. Sandeep Bhuta
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  13. Stefan Blum
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  14. Mike Boggild
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  15. Karyn Boundy
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  16. Bruce J. Brew
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  17. Wallace Brownlee
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  18. Helmut Butzkueven
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  19. William M. Carroll
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  20. Celia Chen
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  21. Alan Coulthard
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  22. Russell C. Dale
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  23. Chandi Das
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  24. Keith Dear
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  25. Marzena J. Fabis-Pedrini
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  26. David Fulcher
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  27. David Gillis
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  28. Simon Hawke
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  29. Robert Heard
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  30. Andrew P. D. Henderson
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  31. Saman Heshmat
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  32. Suzanne Hodgkinson
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  33. Sofia Jimenez-Sanchez
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  34. Trevor J. Kilpatrick
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  35. John King
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  36. Chris Kneebone
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  37. Andrew J. Kornberg
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  38. Jeannette Lechner-Scott
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  39. Ming-Wei Lin
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  40. Christopher Lynch
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  41. Richard A. L. Macdonnell
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  42. Deborah F. Mason
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  43. Pamela A. McCombe
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  44. Jennifer Pereira
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  45. John D. Pollard
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  46. Stephen W. Reddel
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  47. Cameron Shaw
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  48. Judith Spies
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  49. James Stankovich
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  50. Ian Sutton
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  51. Steve Vucic
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  52. Michael Walsh
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  53. Richard C. Wong
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  54. Eppie M. Yiu
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  56. Allan G. Kermode
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  60. Bruce V. Taylor
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  61. Ernest Willoughby
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  62. Robert J. Wilson
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  63. Fabienne Brilot
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  64. Angela Vincent
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  65. Patrick Waters
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  66. Simon A. Broadley
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DA, MHB, SBh, SBl, MBo, KB, BJB, SAB, MBr, WBr, HB, WMC, CC, AC, RCD, CD, KD, DG, SHa, RH, APDH, SHo, AGK, TJK, JK, CK, JL-S, CL, RALM, MPMa, DFM, PAMcC, CO’G, JPa, JPe, JDP, KMP, SWR, CS, MS, JSp, JSt, IS, BVT, AV, SV, MWa, PW, EW, RJW and RCW conceived and designed the study. SA, SAB, WBu, CSB, LC, KD, MJF-P, DG, SHe, SJ-S, M-WL, KMP, RS, JSt, BVT, PW, RJW, MWo and EMY conducted the analyses. WBu and LC prepared the initial draft and SA, MHB, BJB, FB, SAB, WMC, RCD, KD, MJF-P, DF, APDH, SHo, AJK, JL-S, M-WL, MPMa, PAMcC, MPMe, KMP, SR, RS, MS, BVT, AV, SV, MWa, PW, EW, RJW, RCW, MWo and EMY contributed to revisions. All authors approved the final draft.

Corresponding author

Correspondence to Simon A. Broadley.

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Conflicts of interest

MHB has received honoraria for participation in advisory boards and travel sponsorship from Novartis, BioCSL, Genzyme and Biogen Idec. MBo has received travel sponsorship and honoraria from Sanofi-Genzyme, Teva, Novartis, Biogen Idec and Roche. BJB has received honoraria as a board member for GlaxoSmithKline, Biogen Idec, ViiV Healthcare and Merck Serono, has received speaker honoraria from ViiV Healthcare, Boehringer Ingelheim, Abbott, Abbvie, and Biogen Idec; has received travel sponsorship from Abbott and Viiv Healthcare, and has received research support funding from EI Lilly, GlaxoSmithKline, ViiV Healthcare and Merck Serono. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Scherring, Biogen-Idec, Merck-Serono, Novartis, and Sanofi-Genzyme, has received speakers honoraria from Biogen-Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme, and was the recipient of an unencumbered research grant from Biogen-Idec. HB has received honoraria for serving on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Genzyme, has received conference travel sponsorship from Novartis and Biogen Idec, has received honoraria for speaking and acting as Chair at educational events organised by Novartis, Biogen Idec, Medscape and Merck Serono, serves on steering committees for trials conducted by Biogen Idec and Novartis, is chair (honorary) of the MSBase Foundation, which has received research support from Merck Serono, Novartis, Biogen Idec, Genzyme Sanofi and CSL Biopharma and has received research support form Merck Serono. WMC has been the recipient of travel sponsorship from, and provided advice to, Bayer Schering Pharma, Biogen-Idec, Novartis, Genzyme, Sanofi-Aventis, BioCSL and Merck-Serono. RCD has received research funding from the National Health and Medical Research Council, MS Research Australia, Star Scientific Foundation, Pfizer Neuroscience, Tourette Syndrome Association, University of Sydney, and the Petre Foundation and has received honoraria from Biogen-Idec and Bristol-Myers Squibb as an invited speaker MjF-P has received travel sponsorship from Biogen Australia and New Zealand. RH has received honoraria, educational support and clinic funding from Novartis, Biogen Idec, Genzyme and BioCSL. AGK has received scientific consulting fees and/or lecture honoraria from Bayer, BioCSL, Biogen-Idec, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva. TJK has received travel sponsorship from Novartis, BioCSL, Novartis, Merck Serono and Biogen Idec, has received speaker honoraria from Biogen Idec, BioCSL, Merck Serono, Teva, Genzyme and Novartis, has received research support from Biogen Idec, Genzyme, GlaxoSmithKline, Bayer-Schering and Merck Serono, and has received scientific consulting fees from GlaxoSmithKline China, Biogen-Idec and Novartis. JK has received remuneration for advisory board activities and presentations from Bayer Healthcare, Biogen Idec, BioCSL, Genzyme and Novartis. CK has received travel support, honoraria and advisory board payments from Biogen Idec, Bayer, Genzyme, Novartis and Serono. JL-S has received unencumbered funding as well as honoraria for presentations and membership on advisory boards from Sanofi Aventis, Biogen Idec, Bayer Health Care, CSL, Genzyme, Merck Serono, Novartis Australia and Teva. RALM has received honoraria for attendance at advisory boards and travel sponsorship from Bayer, Biogen, CSL, Merck, Novartis, Roche, Celgene, Teva and Genzyme. MPMa has received travel sponsorship, honoraria, trial payments, research and clinical support from Bayer Schering, Biogen Idec, BioCSL, Genzyme, Novartis and Sanofi Aventis Genzyme. DFM has received honoraria for attendance at advisory boards from Biogen-Idec and Novartis, and travel sponsorship from Bayer-Scherring, Biogen-Idec, and Sanofi-Genzyme. PAMcC has received honoraria or travel sponsorship from Novatis, Sanofi-Aventis and Biogen Idec. JAP has received travel sponsorship, honoraria for presentations and membership on advisory boards from Biogen Idec and Novartis and Sanofi Aventis. JDP has received honoraria for seminars or advisory boards from Teva, Biogen, Sanofi-Genzyme, Novartis, Merck, Bayer and research grants or fellowships from Merck, Novartis, Bayer, Biogen, Sanofi-Genzyme and Teva SWR has received travel sponsorship, honoraria, trial payments, research and clinical support from Aspreva, Baxter, Bayer Schering, Biogen Idec, BioCSL, Genzyme, Novartis, Sanofi Aventis Genzyme and Servier, and is a director of Medical Safety Systems Pty Ltd. CPS has received travel sponsorship from Biogen Idec, Novartis and Bayer-Schering. IS has received remuneration for Advisory Board activities from Biogen, CSL, and Bayer Schering and educational activities with Biogen, CSL and travel sponsorship from Biogen, Novartis and Bayer Schering. MS has received research support from Novartis, Biogen Idec and BioCSL. JSp has received honoraria for lectures and participation in advisory boards, and travel sponsorship from Novartis, BioCSL, Genzyme and Biogen Idec. BVT has received travel sponsorship from Novartis and Bayer Schering. AV and the University of Oxford hold patents and receive royalties for antibody testing. PW and the University of Oxford hold patents for antibody assays and have received royalties, has received speaker honoraria from Biogen Idec and Euroimmun AG, and travel grants from the Guthy-Jackson Charitable Foundation. EW has received honoraria for participation in advisory boards from Biogen-Idec and Novartis, travel sponsorship from Biogen-Idec, Bayer-Schering and Teva and is an investigator in clinical trials funded by Biogen-Idec and Teva. DA, SBh, SBl, KB, MBr, WBr, WBu, CSB, CCM, LC, AC, CD, KD, DF, DG, SHa, APDH, SHe, SHo, SJ-S, AJK, M-WL, CL, CO’G, MPM, CS, RS, JSt, AV, SV, MWa, RJW, RCW, MWo and EMY report no disclosures.

Ethical standard

Human Research Ethics Commitee approval was sought and obtained for all 23 clinical site and the 5 laboratories involved in this research.

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All participants provided written, informed consent.

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Bukhari, W., Clarke, L., O’Gorman, C. et al. The clinical profile of NMOSD in Australia and New Zealand. J Neurol 267, 1431–1443 (2020). https://doi.org/10.1007/s00415-020-09716-4

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  • DOI: https://doi.org/10.1007/s00415-020-09716-4

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