Semin Neurol 2021; 41(03): 269-279
DOI: 10.1055/s-0041-1725152
Review Article

Immune-Mediated Myelopathies: A Review of Etiologies, Diagnostic Approach, and Therapeutic Management

Lama Abdel-Wahed
1   Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
,
Tracey A. Cho
1   Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa
› Author Affiliations
Funding None.

Abstract

Myelopathy is a broad term used to describe a heterogeneous group of disorders that affects the spinal cord; the focus of this article will be a subgroup of these disorders with an autoimmune and inflammatory-based pathology. Symptoms typically develop over hours or days and then worsen over a matter of days to weeks, but sometimes can have a more insidious or subacute presentation, which can make the diagnosis more puzzling. Despite relatively low incidence rates, almost a third of affected patients are left with severely disabling symptoms. Prompt recognition of the underlying etiology is essential so that a specific targeted therapy can be implemented for optimal outcomes. The authors discuss a systematic approach to immune-mediated myelopathies, with a focus on the unique characteristics of each that may aid in diagnosis.

Note

All authors had access to the data and played a role in writing the manuscript and have approved the final version for submission.




Publication History

Article published online:
24 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 West TW. Transverse myelitis--a review of the presentation, diagnosis, and initial management. Discov Med 2013; 16 (88) 167-177
  • 2 Greenberg BM, Frohman EM. Immune-mediated myelopathies. Continuum (Minneapolis, Minn). 2015; 21 (1 Spinal Cord Disorders): 121-131
  • 3 Dubey D, Pittock SJ, Krecke KN. et al. Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol 2019; 76 (03) 301-309
  • 4 Cho TA, Bhattacharyya S. Approach to Myelopathy. Continuum (Minneapolis, Minn). 2018; 24 (2, Spinal Cord Disorders): 386-406
  • 5 Zalewski NL, Flanagan EP. Autoimmune and paraneoplastic myelopathies. Semin Neurol 2018; 38 (03) 278-289
  • 6 Scott TF, Frohman EM, De Seze J, Gronseth GS, Weinshenker BG. Therapeutics and Technology Assessment Subcommittee of American Academy of Neurology. Evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 77 (24) 2128-2134
  • 7 de Seze J, Stojkovic T, Breteau G. et al. Acute myelopathies: clinical, laboratory and outcome profiles in 79 cases. Brain 2001; 124 (Pt 8): 1509-1521
  • 8 Zalewski NL, Flanagan EP, Keegan BM. Evaluation of idiopathic transverse myelitis revealing specific myelopathy diagnoses. Neurology 2018; 90 (02) e96-e102
  • 9 Durel CA, Marignier R, Maucort-Boulch D. et al. Clinical features and prognostic factors of spinal cord sarcoidosis: a multicenter observational study of 20 BIOPSY-PROVEN patients. J Neurol 2016; 263 (05) 981-990
  • 10 Katz Sand I. Neuromyelitis optica spectrum disorders. Continuum (Minneap Minn) 2016; 22 (03) 864-896
  • 11 Wendebourg MJ, Nagy S, Derfuss T, Parmar K, Schlaeger R. Magnetic resonance imaging in immune-mediated myelopathies. J Neurol 2019
  • 12 Misra UK, Kalita J. Can electromyography predict the prognosis of transverse myelitis?. J Neurol 1998; 245 (11) 741-744
  • 13 Wingerchuk DM. Immune-Mediated Myelopathies. Continuum (Minneapolis, Minn) 2018; 24 (2, Spinal Cord Disorders): 497-522
  • 14 Dormegny L, Chibbaro S, Ganau M, Santin M, Kremer L, Proust F. Biopsying a spinal cord lesion: a diagnostic dilemma. Case report and review of literature. Neurochirurgie 2018; 64 (06) 425-430
  • 15 Zalewski NL, Rabinstein AA, Krecke KN. et al. Characteristics of spontaneous spinal cord infarction and proposed diagnostic criteria. JAMA Neurol 2019; 76 (01) 56-63
  • 16 Winkelmann A, Rommer PS, Hecker M, Zettl UK. Intravenous immunoglobulin treatment in multiple sclerosis: a prospective, rater-blinded analysis of relapse rates during pregnancy and the postnatal period. CNS Neurosci Ther 2019; 25 (01) 78-85
  • 17 Zalewski NL, Morris PP, Weinshenker BG. et al. Ring-enhancing spinal cord lesions in neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry 2017; 88 (03) 218-225
  • 18 Pohl D, Rostasy K, Reiber H, Hanefeld F. CSF characteristics in early-onset multiple sclerosis. Neurology 2004; 63 (10) 1966-1967
  • 19 Beseler C, Vollmer T, Graner M, Yu X. The complex relationship between oligoclonal bands, lymphocytes in the cerebrospinal fluid, and immunoglobulin G antibodies in multiple sclerosis: indication of serum contribution. PLoS One 2017; 12 (10) e0186842
  • 20 Repovic P. Management of multiple sclerosis relapses. Continuum (Minneap Minn) 2019; 25 (03) 655-669
  • 21 Sato DK, Callegaro D, Lana-Peixoto MA. et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology 2014; 82 (06) 474-481
  • 22 Marignier R, Bernard-Valnet R, Giraudon P. et al; NOMADMUS Study Group. Aquaporin-4 antibody-negative neuromyelitis optica: distinct assay sensitivity-dependent entity. Neurology 2013; 80 (24) 2194-2200
  • 23 Flanagan EP, Weinshenker BG, Krecke KN. et al. Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders. JAMA Neurol 2015; 72 (01) 81-87
  • 24 Romeo AR, Segal BM. Treatment of neuromyelitis optica spectrum disorders. Curr Opin Rheumatol 2019; 31 (03) 250-255
  • 25 Elsone L, Panicker J, Mutch K, Boggild M, Appleton R, Jacob A. Role of intravenous immunoglobulin in the treatment of acute relapses of neuromyelitis optica: experience in 10 patients. Mult Scler 2014; 20 (04) 501-504
  • 26 Pittock SJ, Berthele A, Fujihara K. et al. Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder. N Engl J Med 2019; 381 (07) 614-625
  • 27 Cree BAC, Bennett JL, Kim HJ. et al; N-MOmentum study investigators. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial. Lancet 2019; 394 (10206): 1352-1363
  • 28 Traboulsee A, Greenberg BM, Bennett JL. et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol 2020; 19 (05) 402-412
  • 29 Chen JJ, Flanagan EP, Jitprapaikulsan J. et al. Myelin oligodendrocyte glycoprotein antibody-positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol 2018; 195: 8-15
  • 30 Cobo-Calvo A, Vukusic S, Marignier R. Clinical spectrum of central nervous system myelin oligodendrocyte glycoprotein autoimmunity in adults. Curr Opin Neurol 2019; 32 (03) 459-466
  • 31 Patterson K, Iglesias E, Nasrallah M. et al. Anti-MOG encephalitis mimicking small vessel CNS vasculitis. Neurol Neuroimmunol Neuroinflamm 2019; 6 (02) e538
  • 32 Sundaram S, Nair SS, Jaganmohan D, Unnikrishnan G, Nair M. Relapsing lumbosacral myeloradiculitis: An unusual presentation of MOG antibody disease. Mult Scler 2020; 26 (04) 509-511
  • 33 Hyun JW, Woodhall MR, Kim SH. et al. Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry 2017; 88 (10) 811-817
  • 34 de Mol CL, Wong Y, van Pelt ED. et al. The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults. Mult Scler 2019; 1352458519845112
  • 35 Weber MS, Derfuss T, Metz I, Brück W. Defining distinct features of anti-MOG antibody associated central nervous system demyelination. Ther Adv Neurol Disorder 2018; 11: 1756286418762083
  • 36 Narayan R, Simpson A, Fritsche K. et al. MOG antibody disease: a review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord 2018; 25: 66-72
  • 37 Jarius S, Ruprecht K, Kleiter I. et al; in cooperation with the Neuromyelitis Optica Study Group (NEMOS). MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation 2016; 13 (01) 280
  • 38 Cobo-Calvo Á, Sepúlveda M, Bernard-Valnet R. et al. Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: clinical and prognostic implications. Mult Scler 2016; 22 (03) 312-319
  • 39 Ramanathan S, Mohammad S, Tantsis E. et al; Australasian and New Zealand MOG Study Group. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination. J Neurol Neurosurg Psychiatry 2018; 89 (02) 127-137
  • 40 Hacohen Y, Banwell B. Treatment approaches for MOG-Ab-associated demyelination in children. Curr Treat Options Neurol 2019; 21 (01) 2
  • 41 Winter M, Baksmeier C, Steckel J. et al. Dose-dependent inhibition of demyelination and microglia activation by IVIG. Ann Clin Transl Neurol 2016; 3 (11) 828-843
  • 42 Pohl D, Alper G, Van Haren K. et al. Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology 2016; 87 (09, Suppl 2): S38-S45
  • 43 Koelman DL, Chahin S, Mar SS. et al. Acute disseminated encephalomyelitis in 228 patients: a retrospective, multicenter US study. Neurology 2016; 86 (22) 2085-2093
  • 44 Kerr DA, Ayetey H. Immunopathogenesis of acute transverse myelitis. Curr Opin Neurol 2002; 15 (03) 339-347
  • 45 Zijdewind JM, Dijkmans AC, Purmer IM, Treurniet F, Wirtz PW. An aggressive case of PCR negative varicella zoster virus induced transverse myelitis. Neurol Sci 2014; 35 (06) 961-963
  • 46 Sendi P, Hirzel C, Bloch A. et al. Bartonella-associated transverse myelitis. Emerg Infect Dis 2017; 23 (04) 712-713
  • 47 Grill MF. Infectious Myelopathies. Continuum (Minneapolis, Minn). 2018; 24 (2, Spinal Cord Disorders): 441-473
  • 48 Cho TA, Vaitkevicius H. Infectious myelopathies. Continuum (Minneapolis, Minn). 2012; 18 (6 Infectious Disease): 1351-1373
  • 49 Hopkins SE, Elrick MJ, Messacar K. Acute flaccid myelitis-keys to diagnosis, questions about treatment, and future directions. JAMA Pediatr 2019; 173 (02) 117-118
  • 50 Messacar K, Schreiner TL, Van Haren K. et al. Acute flaccid myelitis: a clinical review of US cases 2012-2015. Ann Neurol 2016; 80 (03) 326-338
  • 51 Krumholz A, Stern BJ. Neurologic manifestations of sarcoidosis. Handb Clin Neurol 2014; 119: 305-333
  • 52 Fritz D, Voortman M, van de Beek D, Drent M, Brouwer MC. Many faces of neurosarcoidosis: from chronic meningitis to myelopathy. Curr Opin Pulm Med 2017; 23 (05) 439-446
  • 53 Flanagan EP, Kaufmann TJ, Krecke KN. et al. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol 2016; 79 (03) 437-447
  • 54 Tavee JO, Stern BJ. Neurosarcoidosis. Continuum (Minneapolis, Minn) 2014; 20 (3 Neurology of Systemic Disease): 545-559
  • 55 Stern BJ, Royal III W, Gelfand JM. et al. Definition and consensus diagnostic criteria for neurosarcoidosis: from the Neurosarcoidosis Consortium Consensus Group. JAMA Neurol 2018; 75 (12) 1546-1553
  • 56 Gelfand JM, Bradshaw MJ, Stern BJ. et al. Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series. Neurology 2017; 89 (20) 2092-2100
  • 57 Cohen Aubart F, Bouvry D, Galanaud D. et al. Long-term outcomes of refractory neurosarcoidosis treated with infliximab. J Neurol 2017; 264 (05) 891-897
  • 58 Bruè C, Mariotti C, Rossiello I, Saitta A, Giovannini A. Demyelinizing neurological disease after treatment with tumor necrosis factor-α antagonists. Case Rep Ophthalmol 2016; 7 (02) 345-353
  • 59 Birnbaum J, Petri M, Thompson R, Izbudak I, Kerr D. Distinct subtypes of myelitis in systemic lupus erythematosus. Arthritis Rheum 2009; 60 (11) 3378-3387
  • 60 Barreras P, Fitzgerald KC, Mealy MA. et al. Clinical biomarkers differentiate myelitis from vascular and other causes of myelopathy. Neurology 2018; 90 (01) e12-e21
  • 61 Correale J, Fiol M. Activation of humoral immunity and eosinophils in neuromyelitis optica. Neurology 2004; 63 (12) 2363-2370
  • 62 Tintoré M, Rovira A, Brieva L. et al. Isolated demyelinating syndromes: comparison of CSF oligoclonal bands and different MR imaging criteria to predict conversion to CDMS. Mult Scler 2001; 7 (06) 359-363
  • 63 Gastaldi M, Zardini E, Leante R. et al. Cerebrospinal fluid analysis and the determination of oligoclonal bands. Neurol Sci 2017; 38 (02, Suppl 2) 217-224