Document Type: Original Article

Authors

1 Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Neurology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada

4 Department of Radiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 Young Researchers and Elite Club, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran

Abstract

Background: The aim of this study was to evaluate the status of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with transverse
myelitis (TM) and compare the clinical and imaging characteristics of MOG immunoglobulin G (IgG)-positive with negative cases.
Methods: This cohort study enrolled 71 patients diagnosed with new-onset of TM who were being followed at a referral university clinic in Isfahan, Iran, from November 2016 to January 2019. Magnetic resonance imaging (MRI) images and blood samples for anti-MOG, anti-aquaporin 4 (anti-AQP4) (using the cell-based technique), and vasculitis-related antibodies were collected from patients. Outcomes were assessed by the evolution of the Expanded Disability Status Scale (EDSS) score and brain and spinal cord imaging findings 
within three months. All patients underwent imaging and clinical assessment during a mean period of one year as a follow-up. We compared the characteristics of clinical and radiological outcomes in MOG-IgG-positive and negative cases.
Results: Of the total population studied, there were 26.8% men and 73.2% women, with a mean age of
33 ± 10 years. 12 (16.9%) patients were seropositive for MOG antibody and 17 (89.5%) were positive for
anti-AQP4 antibodies. There was no significant association between anti-MOG antibody seropositivity and age, gender distribution, the presence of other autoimmune diseases, and number and interval of relapses. However, the involvement site of the spine at first imaging was significantly different between seronegative and seropositive patients.
Conclusion: In patients with MOG antibody disease (MOG-AD) TM, the MRI findings suggest a preferential involvement of the cervical-thoracic section in seropositive cases which may help differentiate from non-MOG demyelination TM.

Keywords

  1. Frohman EM, Wingerchuk DM. Clinical practice. Transverse myelitis. N Engl J Med 2010; 363(6): 564-72.
  2. Espinosa G, Mendizabal A, Minguez S, Ramo-Tello C, Capellades J, Olive A, et al. Transverse myelitis affecting more than 4 spinal segments associated with systemic lupus erythematosus: Clinical, immunological, and radiological characteristics of 22 patients. Semin Arthritis Rheum 2010; 39(4): 246-56.
  3. Rodriguez Y, Rojas M, Pacheco Y, Acosta-Ampudia Y, Ramirez-Santana C, Monsalve DM, et al. Guillain-Barre syndrome, transverse myelitis and infectious diseases. Cell Mol Immunol 2018; 15(6): 547-62.
  4. Khalid S, Colaco CB. Transverse myelitis with anti-ro antibodies as a predictor of recurrence. Rheumatology 2017; 56(suppl_2): 174.
  5. de Seze J, Stojkovic T, Breteau G, Lucas C, Michon-Pasturel U, Gauvrit JY, et al. Acute myelopathies: Clinical, laboratory and outcome profiles in 79 cases. Brain 2001; 124(Pt 8): 1509-21.
  6. Transverse Myelitis Consortium Working Group. Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 2002; 59(4): 499-505.
  7. Ghosh P, Roy K, Bothra SJ, Sandeep BV. Primary cervical intradural extramedullary primitive neuroectodermal tumors presented as acute transverse myelitis: A case report and review of literature. Indian Journal of Neurosurgery 2017; 06(01): 067-71.
  8. Rana D, Rohatgi A, Patel S, Dave N, Agarwal R, Gupta P. Longitudinally extensive transverse myelitis as presenting manifestation of lung adenocarcinoma. Indian J Med Paediatr Oncol 2018; 39: 106.
  9. Vermersch P, Outteryck O, Ferriby D, Zephir H. Myelitis as a differential diagnosis of spinal cord tumors. Neurochirurgie 2017; 63(5): 349-55. [In French].
  10. Ivanovic J, Mesaros S, Drulovic J. Successful treatment of paraneoplastic longitudinally extensive transverse myelitis (LETM): A 16-month clinical-spinal MRI follow-up. Mult Scler Relat Disord 2018; 26: 207-10.
  11. Cobo-Calvo A, Sepulveda M, Bernard-Valnet R, Ruiz A, Brassat D, Martinez-Yelamos S, et al. Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: Clinical and prognostic implications. Mult Scler 2016; 22(3): 312-9.
  12. Ruiz-Gaviria R, Baracaldo I, Castaneda C, Ruiz-Patino A, Acosta-Hernandez A, Rosselli D. Specificity and sensitivity of aquaporin 4 antibody detection tests in patients with neuromyelitis optica: A meta-analysis. Mult Scler Relat Disord 2015; 4(4): 345-9.
  13. Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev 2016; 15(4): 307-24.
  14. Ketelslegers IA, Van Pelt DE, Bryde S, Neuteboom RF, Catsman-Berrevoets CE, Hamann D, et al. Anti-MOG antibodies plead against MS diagnosis in an Acquired Demyelinating Syndromes cohort. Mult Scler 2015; 21(12): 1513-20.
  15. Greenberg BM, Thomas KP, Krishnan C, Kaplin AI, Calabresi PA, Kerr DA. Idiopathic transverse myelitis: corticosteroids, plasma exchange, or cyclophosphamide. Neurology 2007; 68(19): 1614-7.
  16. Hawkes CH, Giovannoni G. The McDonald criteria for multiple sclerosis: Time for clarification. Mult Scler 2010; 16(5): 566-75.
  17. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 2015; 85(2): 177-89.
  18. Hyun JW, Kim SH, Huh SY, Kim W, Yun J, Joung A, et al. Idiopathic aquaporin-4 antibody negative longitudinally extensive transverse myelitis. Mult Scler 2015; 21(6): 710-7.
  19. Sato DK, Callegaro D, Lana-Peixoto MA, Waters PJ, de Haidar Jorge FM, Takahashi T, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82(6): 474-81.
  20. Hoftberger R, Sepulveda M, Armangue T, Blanco Y, Rostasy K, Calvo AC, et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler 2015; 21(7): 866-74.
  21. Probstel AK, Dornmair K, Bittner R, Sperl P, Jenne D, Magalhaes S, et al. Antibodies to MOG are transient in childhood acute disseminated encephalomyelitis. Neurology 2011; 77(6): 580-8.
  22. Rostasy K, Mader S, Schanda K, Huppke P, Gartner J, Kraus V, et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol 2012; 69(6): 752-6.
  23. Idiman E, Idiman F, Kaya M, Hasankoyoglu O, Kaya D, Limoncu H, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies in turkish population: A comparative study. Neurology 2018; 90(15 Supplement): P6.397.
  24. Probstel AK, Rudolf G, Dornmair K, Collongues N, Chanson JB, Sanderson NS, et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. J Neuroinflammation 2015; 12: 46.
  25. Kitley J, Waters P, Woodhall M, Leite MI, Murchison A, George J, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol 2014; 71(3): 276-83.
  26. Baumann M, Sahin K, Lechner C, Hennes EM, Schanda K, Mader S, et al. Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry 2015; 86(3): 265-72.
  27. Ramanathan S, Reddel SW, Henderson A, Parratt JD, Barnett M, Gatt PN, et al. Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurol Neuroimmunol Neuroinflamm 2014; 1(4): e40.
  28. Saadoun S, Waters P, Owens GP, Bennett JL, Vincent A, Papadopoulos MC. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol Commun 2014; 2: 35.
  29. Ikeda K, Kiyota N, Kuroda H, Sato DK, Nishiyama S, Takahashi T, et al. Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody. Mult Scler 2015; 21(5): 656-9.
  30. Shiga Y, Kamimura T, Shimoe Y, Takahashi T, Kaneko K, Kuriyama M. Anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive varicella-zoster virus myelitis presenting as longitudinally extensive transverse myelitis: A case report. Rinsho Shinkeigaku 2017; 57(10): 579-83.
  31. Pandit L, Mustafa S, Uppoor R, Nakashima I, Takahashi T, Kaneko K. Reversible paraspinal muscle hyperintensity in anti-MOG antibody-associated transverse myelitis. Neurol Neuroimmunol Neuroinflamm 2018; 5(1): e412.
  32. Symmonds M, Waters PJ, Kuker W, Leite MI, Schulz UG. Anti-MOG antibodies with longitudinally extensive transverse myelitis preceded by CLIPPERS. Neurology 2015; 84(11): 1177-9.