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Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up

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Abstract

Severe, recurrent or bilateral optic neuritis (ON) often falls within the neuromyelitis optica spectrum disorders (NMOSD), but the diagnosis can be particularly challenging and has important treatment implications. We report the features, course and outcomes of patients presenting with atypical ON when isolated at onset. We retrospectively analyzed 69 sequential patients referred to a single UK NMO center with isolated ON at onset. Aquaporin-4 antibody (AQP4-Ab) assessment was performed in all patients and IgG1 myelin-oligodenrocyte glycoprotein (MOG-Ab) in AQP4-Abneg patients. 37 AQP4-Ab positive (AQP4-Abpos) and 32 AQP4-Ab negative (AQP4-Ab neg) patients (8 with MOG-Ab) were identified. The AQP4-Abneg group included heterogeneous diagnoses: multiple sclerosis (MS), NMO, relapsing isolated ON (RION), monophasic isolated ON and relapsing acute disseminated encephalomyelitis (ADEM)-like syndromes. Compared to AQP4-Abneg patients, AQP4-Abpos patients had a worse residual visual outcome from first attack (median VFSS 4 vs. 0, p = 0.010) and at last assessment (median VFSS 5 versus 2, p = 0.005). However, AQP4-Abneg patients with RION also had poor visual outcome. Up to 35 % of AQP4-Abneg patients developed a LETM and two developed low positivity for AQP4-Ab over time. Eight AQP4-Abneg patients (25 %) were MOG-Ab positive, covering a range of phenotypes excluding MS; the first ON attack was often bilateral and most had relapsing disease with a poor final visual outcome [VFSS 4, range (0–6)]. In conlcusion, AQP4-Ab positivity is confirmed as a predictor of poor visual outcome but AQP4-Abneg RION also had a poor visual outcome. Of those without AQP4-Ab, 25 % had MOG-Ab and another 25 % developed MS; thus, MOG-Ab is associated with AQP4-Abneg non-MS ON.

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Acknowledgments

We gratefully acknowledge the UK National Specialised Commissioning Team for funding the Neuromyelitis Optica service in Oxford.

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Authors and Affiliations

  1. Nuffield Department of Clinical Neurosciences, Level 3 West Wing, Oxford University Hospitals NHS Trust, University of Oxford, Headley Way, Oxford, OX3 9DU, UK

    L. Piccolo, G. Tackley, M. Juryńczyk, J. Domingos, R. Gore, M. I. Leite & J. Palace

  2. IRCCS C. Mondino, University of Pavia, Pavia, Italy

    L. Piccolo

  3. Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Level 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK

    M. Woodhall, A. Vincent & P. Waters

  4. FMRIB Centre, John Radcliffe Hospital, Oxford University, Headington, Oxford, OX3 9DU, UK

    Y. Kong

  5. Centro Hospitalar do Porto, Hospital de Santo António, Serviço de Neurologia, Porto, Portugal

    J. Domingos

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  1. L. Piccolo
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  2. M. Woodhall
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  3. G. Tackley
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  8. A. Vincent
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  9. P. Waters
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  10. M. I. Leite
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Correspondence to J. Palace.

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Conflicts of interest

Dr. Piccolo reports no disclosures. Dr. Woodhall is funded by NHS National Specialised Commissioning Group for Neuromyelitis optica, UK. Dr. Tackley is funded by NHS National Specialised Commissioning Group for Neuromyelitis optica, UK. Dr. Juryńczyk received research fellowship from the Polish Ministry of Science and Higher Education programme Mobliność Plus (1070/MOB/2013/0). Dr. Kong reports no disclosures. Dr. Domingos reports no disclosures. Rosie Gore reports no disclosures. Prof. Angela Vincent and the University of Oxford hold patents and receive royalties for antibody tests. Dr. Waters has received speaker honoraria from Biogen Idec Japan and Euroimmun AG; holds patents for assays for the detection and antibodies to Lgi1, CASPR2, and GABAAR, and has received royalties. He has received travel grants from the Guthy-Jackson Charitable Foundation.Funding: NHS National Specialised Services for Neuromyelitis and the NIHR Oxford Biomedical Research Centre. Dr. Leite is supported by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK, and by NIHR Oxford Biomedical Research Centre, and has received travel grant and speaking honoraria from Biogen Idec and travel grant from Novartis. Dr. Palace is partly funded by highly specialized services to run a National congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma, Alexion and Bayer Schering, and unrestricted grants from Merck Serono, Novartis, Biogen Idec and Bayer Schering. Her hospital trust receives funds for her role as clinical lead for the RSS, and she has received grants from the MS society and Guthie Jackson Foundation for unrelated research studies.

Ethical standards

This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All patients were consented under ethics number 10/H0606/56.

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415_2015_7983_MOESM1_ESM.tiff

Supplementary Fig. 1. Kaplan–Meier analysis showing cumulative probability of Transverse Myelitis (TM) (A) and Longitudinally Extensive Transverse Myelitis (LETM) (B) relapses over time following first optic neuritis attack (ON). No differences were observed in the probability of TM relapses over time between the two groups (A), but there was an increased likelihood of LETM relapses over time in the AQP4-Ab positive group compared with patients without AQP4-Ab (p < 0.005) (B) (TIFF 6369 kb)

Supplementary material 2 (DOCX 53 kb)

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Piccolo, L., Woodhall, M., Tackley, G. et al. Isolated new onset ‘atypical’ optic neuritis in the NMO clinic: serum antibodies, prognoses and diagnoses at follow-up. J Neurol 263, 370–379 (2016). https://doi.org/10.1007/s00415-015-7983-1

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  • DOI: https://doi.org/10.1007/s00415-015-7983-1

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