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Research paper
Chronic neuropathic pain severity is determined by lesion level in aquaporin 4-antibody-positive myelitis
  1. George Tackley1,
  2. Domizia Vecchio1,2,
  3. Shahd Hamid3,
  4. Maciej Jurynczyk1,
  5. Yazhuo Kong1,
  6. Rosie Gore1,
  7. Kerry Mutch3,
  8. Mark Woodhall1,
  9. Patrick Waters1,
  10. Angela Vincent1,
  11. Maria Isabel Leite1,
  12. Irene Tracey1,
  13. Anu Jacob3,
  14. Jacqueline Palace1
  1. 1Nuffield Department of Clinical Neurosciences, Oxford University Hospitals NHS Trust, University of Oxford, Oxford, UK
  2. 2Department of Neurology, University of Piemonte Orientale, Novara, Italy
  3. 3Department of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool, UK
  1. Correspondence to Dr Jacqueline Palace, Neuroscience Offices West Wing, Level 3 John Radcliffe Hospital Oxford OX3 9DU, UK; jacqueline.palace{at}ndcn.ox.ac.uk

Abstract

Importance Chronic, intractable neuropathic pain is a common and debilitating consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no satisfactory treatment; few studies have yet to explore its aetiology.

Objective To establish if myelitis-associated chronic pain in NMOSD is related to the craniocaudal location of spinal cord lesions.

Method (1) Retrospective cohort of 76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpool's national NMOSD clinics, assessing current pain and craniocaudal location of cord lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab-positive Oxford patients, a subset of the retrospective cohort, assessing current craniocaudal lesion location and current pain.

Results Patients with isolated thoracic cord myelitis at the time of pain onset were significantly more disabled and suffered more pain. Cervical and thoracic lesions that persisted from pain onset to ‘out of relapse’ follow-up (current MRI) had highly significant (p<0.01) opposing effects on pain scores (std. β=−0.46 and 0.48, respectively). Lesion length, total lesion burden and number of transverse myelitis relapses did not correlate with pain.

Conclusions Persistent, caudally located (ie, thoracic) cord lesions in AQP4-Ab-positive patients associate with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length and lesion burden. Although disability correlated with pain in isolation, it became an insignificant predictor of pain when analysed alongside craniocaudal location of lesions.

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Footnotes

  • GT and DV contributed equally.

  • Twitter Follow George Tackley at @gtackley

  • Contributors GT and DV involved in design of the study, data acquisition, analysis and interpretation of the data, drafting and revising the manuscript for intellectual content. SH involved in data acquisition and revising the manuscript for intellectual content. MJ, AV and MIL involved in analysis and interpretation of the data, and revising the manuscript for intellectual content. YK involved in design of the study, data acquisition and interpretation of the data. RG and KM involved in design of the study and data acquisition. MW involved in data acquisition, analysis and interpretation of the data. PW involved in data acquisition, analysis and interpretation of the data, and revising the manuscript for intellectual content. IT involved in conceptualisation of the study. AJ involved in design of the study and revising the manuscript for intellectual content. JP involved in conceptualisation of the study, interpretation of the data and revising the manuscript for intellectual content. Statistical analysis was conducted by GT.

  • Funding Guthy-Jackson Charitable Foundation.

  • Competing interests GT is funded by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK.SH is funded by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK. RG is funded by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK. KM is funded by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK. MW is funded by NHS National Specialised Commissioning Group for Neuromyelitis optica, UK. PW is supported by NHS National Specialised Commissioning Group for Neuromyelitis Optica, UK, and by the NIHR Oxford Biomedical Research Centre. He is a named inventor on patents for antibody assays (No: 20120114666, application No: 1310855.0) and has received royalties. He has received speaker honoraria from Biogen Idec and Euroimmun AG, and travel grants from the Guthy-Jackson Charitable Foundation. AV sat on the Advisory Editorial Board Neurology 2014 and was associate Editor for Brain (2013). She holds a patent with Oxford University for LGI1/CASPR2 antibodies, licensed to Euroimmun AG, and for GABAAR antibodies, in negotiation with Euroimmun AG. She receives royalties from Athena Diagnostics (MuSK assays), Euroimmun AG (LGI1 and CASPR2 assays), and publishing royalties from Clinical Neuroimmunology (Blackwell Publishing, 2005) and Inflammatory and Autoimmune Disorders of the Nervous System in Children (Mac Keith Press 2010). She did consultancy work with Athena Diagnostics for assessing their antibody assays (Ended 2014). She has received speakers' bureaus for scientific conference expenses only. She received funding support from NIHR for antibody work. MIL is involved in AQP4 testing; is supported by the National Health Service National Specialised Commissioning Group for Neuromyelitis Optica and by the National Institute for Health Research Oxford Biomedical Research Centre; and has received speaking honoraria from Biogen Idec and travel grants from Novartis. AJ has received honoraria for speaking on NMO from Biogen Idec and Chugai Pharmaceuticals. He has received a grant from Biogen. He is partly funded by NHS National Specialised Commissioning Group to run a national NMO service, and NIHR to run the Strive clinical trial 2014 (UK). JP is partly funded by highly specialised services to run a national congenital myasthenia service and a national neuromyelitis optica service. She has received conference funding for scientific meetings and honoraria for advisory work from Bayer Schering, Biogen Idec, Chugai Pharma, Merck Serono, Novartis, Ono Pharmaceutical Co. and Teva. She has received unrestricted research grants from Bayer Schering, Biogen Idec, Merck Serono and Novartis. Prospective imaging funded by Guthy-Jackson Charitable Foundation. YK has no competing interests.

  • Ethics approval Oxfordshire REC 07/Q1604/28; London-Hampstead REC 15/L01433; Berkshire REC 13/SC/0238.

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

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