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Journal of Neurology

, Volume 263, Issue 1, pp 140–149 | Cite as

Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes

  • Maciej JuryńczykEmail author
  • Brian Weinshenker
  • Gulsen Akman-Demir
  • Nasrin Asgari
  • David Barnes
  • Mike Boggild
  • Abhijit Chaudhuri
  • Marie D’hooghe
  • Nikos Evangelou
  • Ruth Geraldes
  • Zsolt Illes
  • Anu Jacob
  • Ho Jin Kim
  • Ingo Kleiter
  • Michael Levy
  • Romain Marignier
  • Christopher McGuigan
  • Katy Murray
  • Ichiro Nakashima
  • Lekha Pandit
  • Friedemann Paul
  • Sean Pittock
  • Krzysztof Selmaj
  • Jérôme de Sèze
  • Aksel Siva
  • Radu Tanasescu
  • Sandra Vukusic
  • Dean Wingerchuk
  • Damian Wren
  • Isabel Leite
  • Jacqueline PalaceEmail author
Original Communication

Abstract

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.

Keywords

All demyelinating disease (CNS) Multiple sclerosis Devic’s syndrome Optic neuritis Transverse myelitis 

Notes

Compliance with ethical standards

Conflicts of interest

Dr. Jurynczyk received research fellowship from the Polish Ministry of Science and Higher Education programme Mobliność Plus (1070/MOB/2013/0). Dr. Weinshenker is a member of data safety monitoring boards: Novartis, Biogen Idec and Mitsubishi; Adjudication panel member: MedImmune. Consultant: Elan, GlaxoSmithKline, Ono, CHORD Therapeutics, and Chugai. Editorial board membership: Neurology, the Canadian Journal of Neurological Sciences, and the Turkish Journal of Neurology. Research support: Guthy-Jackson Charitable Foundation. Royalties and patent: RSR Ltd. and Oxford University for a patent regarding AQP4-associated antibodies for diagnosis of neuromyelitis optica. Dr. Akman-Demir reports no disclosures. Dr Asgari reports no disclosures. Dr. Barnes reports no disclosures. Dr. Boggild reports no disclosures. Dr Chaudhuri received travel grants, sponsorship for attending medical congresses, speaker fees and honoraria from: Novartis, Biogen Idec, Bayer-Schering, UCB, Eisai, Terumo BCT and Genzyme. Dr. D’hooghe reports no disclosures. Dr. Evangelou reports no disclosures. Dr. Geraldes reports no disclosures. Dr. Illes reports no disclosures. Dr. Jacob reports no disclosures. Dr. Kim reports no disclosures. Dr. Kleiter reports no disclosures. Dr. Levy reports no disclosures. Dr Marignier was supported by the European research project on rare diseases ERA-Net E-RARE-2 in the frame of the Eugene Devic European Network (EDEN) and Association pour la Recherche contre la Sclerose en Plaques(ARSEP) Foundation. Dr McGuigan has received research funding from Biogen Idec, Novartis, Bayer and Genzyme and honoraria for advisory boards from Biogen Idec, Novartis and Genzyme. Dr. Murray reports no disclosures. Dr. Nakashima reports no disclosures. Dr. Pandit reports no disclosures. Dr Paul was supported by the German Research Foundation (DFG Exc 257), the German Ministry for Education and Research (KKNMS Competence Network Multiple Sclerosis) and the Guthy-Jackson Charitable Foundation. Dr. Pittock reports no disclosures. Dr. Selmaj reports no disclosures. Dr. de Sèze reports no disclosures. Dr. Siva reports no disclosures. Dr. Tanasescu reports no disclosures. Dr. Vukusic reports no disclosures. Dr. Wingerchuk reports no disclosures. Dr. Wren reports no disclosures. Dr. Leite reports no disclosures. Dr. Palace reports no disclosures.

Ethical standards

This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

Informed consent

All patients gave their informed consent to include their anonymised clinical data in the manuscript.

Supplementary material

415_2015_7952_MOESM1_ESM.docx (1.4 mb)
Supplementary material 1 (DOCX 1440 kb)
415_2015_7952_MOESM2_ESM.docx (22 kb)
Supplementary material 2 (DOCX 21 kb)
415_2015_7952_MOESM3_ESM.docx (177 kb)
Supplementary material 3 (DOCX 176 kb)
415_2015_7952_MOESM4_ESM.pdf (30 kb)
The number of MS diagnoses per one expert depending on MS prevalence in the country where the expert practices. (PDF 30 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Maciej Juryńczyk
    • 1
    • 23
    Email author
  • Brian Weinshenker
    • 2
  • Gulsen Akman-Demir
    • 3
  • Nasrin Asgari
    • 4
  • David Barnes
    • 5
  • Mike Boggild
    • 6
  • Abhijit Chaudhuri
    • 7
  • Marie D’hooghe
    • 8
  • Nikos Evangelou
    • 9
  • Ruth Geraldes
    • 10
  • Zsolt Illes
    • 11
  • Anu Jacob
    • 12
  • Ho Jin Kim
    • 13
  • Ingo Kleiter
    • 14
  • Michael Levy
    • 15
  • Romain Marignier
    • 16
  • Christopher McGuigan
    • 17
  • Katy Murray
    • 18
  • Ichiro Nakashima
    • 19
  • Lekha Pandit
    • 20
  • Friedemann Paul
    • 21
  • Sean Pittock
    • 22
  • Krzysztof Selmaj
    • 23
  • Jérôme de Sèze
    • 24
  • Aksel Siva
    • 25
  • Radu Tanasescu
    • 9
    • 26
  • Sandra Vukusic
    • 16
  • Dean Wingerchuk
    • 27
  • Damian Wren
    • 5
  • Isabel Leite
    • 1
  • Jacqueline Palace
    • 1
    Email author
  1. 1.Nuffield Department of Clinical Neurosciences, Level 3West Wing, John Radcliffe Hospital, University of OxfordOxfordUK
  2. 2.Department of NeurologyMayo ClinicRochesterUSA
  3. 3.Department of Neurology, School of MedicineIstanbul Bilim UniversityIstanbulTurkey
  4. 4.Department of Neurology, Vejle Hospital and Neurobiology, Institute of Molecular MedicineUniversity of Southern DenmarkOdenseDenmark
  5. 5.Department of NeurologyAtkinson Morley’s Wing, St George’s HospitalLondonUK
  6. 6.The Townsville HospitalTownsvilleAustralia
  7. 7.Department of NeurologyQueens Hospital Rom Valley WayRomfordUK
  8. 8.Department of NeurologyUniversity Hospital Brussel, Vrije Universiteit BrusselBrusselsBelgium
  9. 9.Division of Clinical Neuroscience, Queens Medical CenterUniversity of NottinghamNottinghamUK
  10. 10.Neuroscience DepartmentSanta Maria Hospital, University of LisbonLisbonPortugal
  11. 11.Department of Neurology, Institute of Clinical Research, OdenseOdense University Hospital, University of Southern DenmarkOdenseDenmark
  12. 12.NMO Clinical ServiceThe Walton CentreLiverpoolUK
  13. 13.Department of NeurologyNational Cancer CenterSeoulSouth Korea
  14. 14.Department of NeurologySt. Josef-Hospital, Ruhr-University BochumBochumGermany
  15. 15.Neuromyelitis Optica ClinicJohn Hopkins UniversityBaltimoreUSA
  16. 16.Service de Neurologie AHopital Neurologique Pierre Wertheimer, Hospices Civils de LyonLyonFrance
  17. 17.University College Dublin, St. Vincent’s University HospitalDublin 4Ireland
  18. 18.Anne Rowling Regenerative Neurology ClinicUniversity of EdinburghEdinburghUK
  19. 19.Department of NeurologyTohoku University School of MedicineSendaiJapan
  20. 20.Nitte UniversityMangaloreIndia
  21. 21.Department of Neurology, NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research CenterCharité-Universitätsmedizin BerlinBerlinGermany
  22. 22.Department of Neurology and Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  23. 23.Department of NeurologyMedical University of LodzLodzPoland
  24. 24.Neurology ServiceUniversity Hospital of StrasbourgStrasbourgFrance
  25. 25.Department of Neurology, Cerrahpasa School of MedicineIstanbul UniversityIstanbulTurkey
  26. 26.Department of Neurology, Neurosurgery and PsychiatryUniversity of Medicine and Pharmacy Carol DavilaBucharestRomania
  27. 27.Mayo Clinic Division of Multiple Sclerosis and Autoimmune NeurologyMayo ClinicScottsdaleUSA

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