MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM)[1] is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.[2]

Presentation

The clinical presentation is variable and largely dependent upon the overall clinical manifestation.

The presence of anti-MOG autoantibodies has been described in association with the following conditions:[3]

The most common presenting phenotypes are acute disseminated encephalomyelitis (ADEM) in children and optic neuritis (ON) in adults.[14] Some of these phenotypes have been studied in detail:

Seronegative neuromyelitis optica

Anti-MOG antibodies have been described in some patients with NMOSD[15][16] who were negative for the aquaporin 4 (AQP-4) antibody. However, most NMOSD is an astrocytopathy, specifically an AQP4 antibody-associated disease, whereas MOG antibody-associated disease is an oligodendrocytopathy, suggesting that these are two separate pathologic entities.[2] Rare cases have been described of patients with antibodies against both AQP4 and MOG. These patients typically have MS-like brain lesions, multifocal spine lesions and optic nerve atrophy.[17] However, the coexistence of both antibodies is still a matter of ongoing debate.[18]

ADEM

The presence of anti-MOG antibodies is more common in children with ADEM.[19][20]

Tumefactive demyelination

Rare cases of anti-MOG antibodies in association with tumefactive multiple sclerosis have been described.[21]

Causes

The reason why anti-MOG auto-antibodies appear remains unknown.

A post-infectious autoimmune process has been proposed as a possible pathophysiologic mechanism.[22] Other reports point to molecular mimicry between MOG and some viruses as a possible etiology.[23]

Histopathology

Demyelinating lesions of MOG-associated encephalomyelitis resemble more those observed in multiple sclerosis[24] than NMO. They are similar to pattern-II multiple sclerosis[10] with T-cells and macrophages surrounding blood vessels, preservation of oligodendrocytes and signs of complement system activation.

Several studies performed during 2020 have shown that MOGAD lesions differ from those seen in MS in many aspects, including their topographical distribution in the CNS, the type of demyelination, and the nature of the inflammatory response.[25]

  • MOGAD demyelination occurs by confluence of small perivenous lesions, generally resulting in a demyelination pattern similar to that seen in acute disseminated encephalomyelitis. Demyelination in MOGAD is associated with complement deposition at the site of active myelin injury, but the degree of complement activation is much less compared to that seen in patients with aquaporin 4 antibody associated neuromyelitis optica (NMO).
  • While in MS the dominant inflammatory reaction is seen around the larger drainage veins in the periventricular tissue and the meninges, in MOGAD the smaller veins and venules are mainly affected.
  • Finally, in MOGAD, infiltrating lymphocytes are mainly CD4+ T-cells with low numbers of CD8+ T-cells and B-cells; the dominant lymphocytes in active MS lesions are tissue resident CD8+ effector memory T-cells and B-cells / plasma cells.

Diagnosis

MOG-IgG is detected by means of so-called cell-based assays (CBA). CBA using live cells transfected with full-length human MOG and employing Fc-specific detection antibodies are the gold standard for anti-MOG antibody testing.[1] Serum is the specimen of choice; cerebrospinal fluid (CSF) analysis is less sensitive compared to serum testing.[1][26][27]

Cerebrospinal fluid oligoclonal bands, the diagnostic mainstay in multiple sclerosis (MS), are rare in MOG-EM, both in adults[28] and in children.[29] If present at all, intrathecal IgG synthesis is low in most patients, often transient, and mainly restricted to acute attacks.[28][29] CSF findings are significantly more pronounced in acute myelitis than in acute ON, which is frequently associated with normal CSF findings, and depends significantly on disease activity (more pronounced during acute attacks), attack severity, and spinal cord lesion extension.[28][29] CSF white cell numbers in MOG-EM may be higher than in MS, especially in acute myelitis, but normal cell numbers do not rule out the disease.[28][29] CSF often contains neutrophil granulocytes and CSF L-lactate levels may be elevated, thus mimicking bacterial meningitis in some cases.[28][29] The intrathecal, polyclonal antiviral immune response (so-called MRZ reaction), which is present in around 63% of MS patients, is absent in MOG-EM.[28][29]

Proposed diagnostic criteria require serum positivity for MOG antibody as detected by CBA, a clinicoradiological presentation consistent with an acquired demyelinating syndrome (VEP can replace radiological evidence only in patients with acute ON), and exclusion of alternative diagnoses;[1][11] in addition, so-called 'red flags' have been defined, which, if present, should prompt physicians to challenge the diagnosis and to prompt re-testing for MOG-IgG, ideally using a second, methodologically different assay.[1][11]

In the young, MRI typically shows ADEM–like lesions and longitudinally extensive transverse myelitis (LETM), whereas optic neuritis and short transverse myelitis are more commonly seen in older patients.[30] However, rare cases of symptomatic MRI-negative MOG-related disease have been described.[31]

Clinical course

Two clinical courses have been described:[32]

  • Monophasic (most common)
  • Relapsing

Treatment

Acute therapy consists of high-dose corticosteroids, IVIG, or plasma exchange, and long-term immunosuppression may be necessary in recurrent cases.[33][34] Anti-MOG positive patients should not be treated with interferons as these may worsen the disease course similar to those with NMOSD.[27] MOG-ON is corticosteroid responsive.[11]

There are also anecdotal reports against using fingolimod[35] or alemtuzumab.[36]

Prognosis

Residual disability develops in 50–80% of patients, with transverse myelitis at onset being the most significant predictor of long-term outcome.. There is emerging evidence that visual outcome in MOG-ON is better in patients who are treated with corticosteroids than without treatment.[11]

Research

Animal models in experimental autoimmune encephalomyelitis, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis" but EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.[37]

History

Reports describing the possible involvement of anti-MOG antibodies in multiple sclerosis and other demyelinating conditions first appeared in the literature in the late 1980s, but evidence to support their role in demyelinating disease was always weak and inconsistent.[38] The possibility of an anti-MOG MS-subtype was considered around 2000.[39]

The turning point was in 2011, when Mader et al. developed a cell-based assay using HEK 293 cells which increased the detection rate of these antibodies in the serum.[40]

Reports about prevalence of anti-MOG in selected Multiple Sclerosis cases began to appear in 2016[9]

Resources

What is MOGAD? from the Siegel Rare Neuroimmune Association

References

  1. 1 2 3 4 5 Jarius S, Paul F, Aktas O, Asgari N, Dale RC, de Seze J, et al. (May 2018). "MOG encephalomyelitis: international recommendations on diagnosis and antibody testing". Journal of Neuroinflammation. 15 (1): 134. doi:10.1186/s12974-018-1144-2. PMC 5932838. PMID 29724224.
  2. 1 2 Ramanathan S, Dale RC, Brilot F (April 2016). "Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination". Autoimmunity Reviews. 15 (4): 307–324. doi:10.1016/j.autrev.2015.12.004. PMID 26708342.
  3. 1 2 3 4 Reindl M, Di Pauli F, Rostásy K, Berger T (August 2013). "The spectrum of MOG autoantibody-associated demyelinating diseases". Nature Reviews. Neurology. 9 (8): 455–461. doi:10.1038/nrneurol.2013.118. PMID 23797245. S2CID 7219279.
  4. ↑ Jarius S, Paul F, Weinshenker BG, Levy M, Kim HJ, Wildemann B (October 2020). "Neuromyelitis optica". Nature Reviews. Disease Primers. 6 (1): 85. doi:10.1038/s41572-020-0214-9. PMID 33093467. S2CID 224825516.
  5. ↑ Hyun JW, Woodhall MR, Kim SH, Jeong IH, Kong B, Kim G, et al. (October 2017). "Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases". Journal of Neurology, Neurosurgery, and Psychiatry. 88 (10): 811–817. doi:10.1136/jnnp-2017-315998. PMID 28684532. S2CID 22732252.
  6. ↑ Baumann M, Hennes EM, Schanda K, Karenfort M, Bajer-Kornek B, Diepold K, et al. (2015). "Clinical characteristics and neuroradiological findings in children with multiphasic demyelinating encephalomyelitis and MOG antibodies". European Journal of Paediatric Neurology. 19 (Supplement 1): S21. doi:10.1016/S1090-3798(15)30066-0.
  7. ↑ Jarius S, Metz I, König FB, Ruprecht K, Reindl M, Paul F, et al. (October 2016). "Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case". Multiple Sclerosis. 22 (12): 1541–1549. doi:10.1177/1352458515622986. PMID 26869529. S2CID 1387384.
  8. ↑ Di Pauli F, Höftberger R, Reindl M, Beer R, Rhomberg P, Schanda K, et al. (December 2015). "Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology". Neurology. 2 (6): e175. doi:10.1212/NXI.0000000000000175. PMC 4635550. PMID 26587556.
  9. 1 2 Spadaro M, Gerdes LA, Krumbholz M, Ertl-Wagner B, Thaler FS, Schuh E, et al. (October 2016). "Autoantibodies to MOG in a distinct subgroup of adult multiple sclerosis". Neurology. 3 (5): e257. doi:10.1212/NXI.0000000000000257. PMC 4949775. PMID 27458601.
  10. 1 2 Tajfirouz DA, Bhatti MT, Chen JJ (November 2019). "Clinical Characteristics and Treatment of MOG-IgG-Associated Optic Neuritis". Current Neurology and Neuroscience Reports. 19 (12): 100. doi:10.1007/s11910-019-1014-z. PMID 31773369. S2CID 208278781.
  11. 1 2 3 4 5 Petzold A, Fraser C, Abegg M, Alroughani R (2022). "Diagnosis and Classification of Optic Neuritis". The Lancet Neurology. 21 (12): 1120–1134. doi:10.1016/S1474-4422(22)00200-9. PMID 36179757.
  12. ↑ Chalmoukou K, Alexopoulos H, Akrivou S, Stathopoulos P, Reindl M, Dalakas MC (August 2015). "Anti-MOG antibodies are frequently associated with steroid-sensitive recurrent optic neuritis". Neurology. 2 (4): e131. doi:10.1212/NXI.0000000000000131. PMC 4496630. PMID 26185777.
  13. ↑ Narayan RN, Wang C, Sguigna P, Husari K, Greenberg B (January 2019). "Atypical Anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor cerebri-like presentations". Multiple Sclerosis and Related Disorders. 27: 30–33. doi:10.1016/j.msard.2018.10.003. PMID 30300850. S2CID 52957303.
  14. ↑ de Mol CL, Wong Y, van Pelt ED, Wokke B, Siepman T, Neuteboom RF, et al. (June 2020). "The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults". Multiple Sclerosis. 26 (7): 806–814. doi:10.1177/1352458519845112. PMC 7294530. PMID 31094288.
  15. ↑ Pröbstel AK, Rudolf G, Dornmair K, Collongues N, Chanson JB, Sanderson NS, et al. (March 2015). "Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype". Journal of Neuroinflammation. 12 (1): 46. doi:10.1186/s12974-015-0256-1. PMC 4359547. PMID 25889963.
  16. ↑ "What's the Role of Myelin Oligodendrocyte Glycoprotein in NMO? | Multiple Sclerosis Discovery Forum". www.msdiscovery.org. Retrieved 2022-06-29.
  17. ↑ Yan Y, Li Y, Fu Y, Yang L, Su L, Shi K, et al. (December 2016). "Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD". Science China Life Sciences. 59 (12): 1270–1281. doi:10.1007/s11427-015-4997-y. PMC 5101174. PMID 26920678.
  18. ↑ Weber MS, Derfuss T, Brück W (August 2018). "Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Central Nervous System Demyelination-A Novel Disease Entity?". JAMA Neurology. 75 (8): 909–910. doi:10.1001/jamaneurol.2018.1055. PMID 29913011. S2CID 49303770.
  19. ↑ Knapp-Tężycka J, Zawadzka M, Knurowska A, Anuszkiewicz K, Stogowski P, Wiśniewska S, et al. (2020). "Zapalenie nerwów wzrokowych, mózgu i rdzenia związane z MOG-IgG (MONEM)" [MOG-IgG-related optic neuritis of the brain and spinal cord (MONEM)]. Polski Przeglad Neurologiczny (in Polish). 16: 46–50. doi:10.5603/PPN.2020.0005. S2CID 216180407.
  20. ↑ Tenembaum S, Waters P, Leite M, Woodhall M, Princich J, Segura M, et al. (2015-04-06). "Spectrum of MOG Autoantibody-Associated Inflammatory Diseases in Pediatric Patients (I4-3A)". Neurology. 84 (14 Supplement). ISSN 0028-3878.
  21. ↑ Shu Y, Long Y, Wang S, Hu W, Zhou J, Xu H, et al. (February 2019). "Brain histopathological study and prognosis in MOG antibody-associated demyelinating pseudotumor". Annals of Clinical and Translational Neurology. 6 (2): 392–396. doi:10.1002/acn3.712. PMC 6389737. PMID 30847372.
  22. ↑ Kakalacheva K, Regenass S, Wiesmayr S, Azzi T, Berger C, Dale RC, et al. (February 2016). "Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein". Viruses. 8 (2): 51. doi:10.3390/v8020051. PMC 4776206. PMID 26907324.
  23. ↑ de Luca V, Martins Higa A, Malta Romano C, Pimenta Mambrini G, Peroni LA, Trivinho-Strixino F, Lima Leite F (May 2019). "Cross-reactivity between myelin oligodendrocyte glycoprotein and human endogenous retrovirus W protein: nanotechnological evidence for the potential trigger of multiple sclerosis". Micron. 120: 66–73. doi:10.1016/j.micron.2019.02.005. PMID 30802755. S2CID 73461847.
  24. ↑ Spadaro M, Gerdes LA, Mayer MC, Ertl-Wagner B, Laurent S, Krumbholz M, et al. (March 2015). "Histopathology and clinical course of MOG-antibody-associated encephalomyelitis". Annals of Clinical and Translational Neurology. 2 (3): 295–301. doi:10.1002/acn3.164. PMC 4369279. PMID 25815356.
  25. ↑ Lassmann H (12 January 2021). "Neuroinflammation: 2021 update". Free Neuropathology. 2: 1. doi:10.17879/freeneuropathology-2021-3166. S2CID 234235224.
  26. ↑ Jarius S, Ruprecht K, Kleiter I, Borisow N, Asgari N, Pitarokoili K, et al. (September 2016). "MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin". Journal of Neuroinflammation. 13 (1): 279. doi:10.1186/s12974-016-0717-1. PMC 5084340. PMID 27788675.
  27. 1 2 Nakashima I (2015). "Anti-myelin oligodendrocyte glycoprotein antibody in demyelinating diseases". Clinical and Experimental Neuroimmunology. 6: 59–63. doi:10.1111/cen3.12262. S2CID 74183244.
  28. 1 2 3 4 5 6 Jarius S, Pellkofer H, Siebert N, Korporal-Kuhnke M, Hümmert MW, Ringelstein M, et al. (September 2020). "Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 1: Results from 163 lumbar punctures in 100 adult patients". Journal of Neuroinflammation. 17 (1): 261. doi:10.1186/s12974-020-01824-2. PMC 7470615. PMID 32883348.
  29. 1 2 3 4 5 6 Jarius S, Lechner C, Wendel EM, Baumann M, Breu M, Schimmel M, et al. (September 2020). "Cerebrospinal fluid findings in patients with myelin oligodendrocyte glycoprotein (MOG) antibodies. Part 2: Results from 108 lumbar punctures in 80 pediatric patients". Journal of Neuroinflammation. 17 (1): 262. doi:10.1186/s12974-020-01825-1. PMC 7470445. PMID 32883358.
  30. ↑ Jurynczyk M, Geraldes R, Probert F, Woodhall MR, Waters P, Tackley G, et al. (March 2017). "Distinct brain imaging characteristics of autoantibody-mediated CNS conditions and multiple sclerosis". Brain. 140 (3): 617–627. doi:10.1093/brain/aww350. PMID 28364548.
  31. ↑ Pérez CA, Garcia-Tarodo S, Troxell R (2019-01-01). "MRI-Negative Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Antibody Spectrum Demyelinating Disease". Child Neurology Open. 6: 2329048X19830475. doi:10.1177/2329048X19830475. PMC 6379793. PMID 30800700.
  32. ↑ Pandit L, Mustafa S, Nakashima I, Takahashi T, Kaneko K (2018). "MOG-IgG-associated disease has a stereotypical clinical course, asymptomatic visual impairment and good treatment response". Multiple Sclerosis Journal - Experimental, Translational and Clinical. 4 (3): 2055217318787829. doi:10.1177/2055217318787829. PMC 6050870. PMID 30038790.
  33. ↑ Oshiro A, Nakamura S, Tamashiro K, Fujihara K (May 2016). "[Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis]". No to Hattatsu = Brain and Development. 48 (3): 199–203. PMID 27349083.
  34. ↑ Zheng Y, Cai MT, Li EC, Fang W, Shen CH, Zhang YX (2021-06-17). "Case Report: Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder Masquerading as Multiple Sclerosis: An Under-Recognized Entity?". Frontiers in Immunology. 12: 671425. doi:10.3389/fimmu.2021.671425. PMC 8249196. PMID 34220818.
  35. ↑ Miyazaki T, Nakajima H, Motomura M, Tanaka K, Maeda Y, Shiraishi H, Tsujino A (April 2016). "A case of recurrent optic neuritis associated with cerebral and spinal cord lesions and autoantibodies against myelin oligodendrocyte glycoprotein relapsed after fingolimod therapy". Rinsho Shinkeigaku = Clinical Neurology. 56 (4): 265–269. doi:10.5692/clinicalneurol.cn-000756. PMID 27010093.
  36. ↑ Seneviratne S, Marriott M, Monif M (2019). "065 Presence of anti-myelin oligodendrocyte glycoprotein antibodies in the serum of two patients following alemtuzumab therapy for suspected multiple sclerosis". Journal of Neurology, Neurosurgery & Psychiatry. 90: A21.2–A21. doi:10.1136/jnnp-2019-anzan.57.
  37. ↑ Kezuka T, Usui Y, Yamakawa N, Matsunaga Y, Matsuda R, Masuda M, et al. (June 2012). "Relationship between NMO-antibody and anti-MOG antibody in optic neuritis". Journal of Neuro-Ophthalmology. 32 (2): 107–110. doi:10.1097/WNO.0b013e31823c9b6c. PMID 22157536. S2CID 46667141.
  38. ↑ Fujihara K, Sato DK, Nakashima I, Takahashi T, Kaneko K, Ogawa R, et al. (8 March 2018). "Myelin oligodendrocyte glycoprotein immunoglobulin G-associated disease: An overview". Clinical and Experimental Neuroimmunology. 9: 48–55. doi:10.1111/cen3.12434.
  39. ↑ Egg R, Reindl M, Deisenhammer F, Linington C, Berger T (October 2001). "Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis". Multiple Sclerosis. 7 (5): 285–289. doi:10.1177/135245850100700503. PMID 11724443. S2CID 23520476.
  40. ↑ Mader S, Gredler V, Schanda K, Rostasy K, Dujmovic I, Pfaller K, et al. (December 2011). "Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders". Journal of Neuroinflammation. 8: 184. doi:10.1186/1742-2094-8-184. PMC 3278385. PMID 22204662.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.