Current research situation of the characteristics of recurrent optic neuritis and the pathogenesis of optic neuritis_Chinese Journal of Ocular Fundus Diseases

Authors：

Liang Xuemei ,  Cao Shan

Nanning Aier Eye Hospital, Nanning 530003, China;

Corresponding author：

Cao Shan, Email: caoshan045@163.com

Keywords：

Optic neuritis/etiology; Review; Recurrent optic neuritis

DOI：

10.3760/cma.j.issn.1005-1015.2019.03.020

Video：

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Abstract Full text Figures/Tables Video References Cited by

Optic neuritis (ON) is one of the symptom of a central nervous system demyelinating, systemic or infectious disease. The pathogenetic mechanism of ON is still not completely clear, and its core is inflammation and immune that occurred in the optic nerve axons, and apoptosis of RGC was induced. Few patients experience recurrent episodes after treatment, presenting a remission - recurrence course of polyphasic disease, named recurrent ON (RON). Two forms of RON have been assigned: recurrent isolated optic neuritis, which is a chronic corticosteroid-dependent optic neuropathy with intermittent acute relapses, and recurrent isolated optic neuritis, which is a non-progressive relapsing ON without steroid dependence. Recurrence of ON causes cumulative damage to the optic nerve lesions and impaired visual signal transmission, thus causing irreversible damage to vision. Therefore, it is very important to have a deep understanding of the pathogenesis of ON and the clinical characteristics of RON, so as to better conduct clinical treatment.

Citation： Liang Xuemei, Cao Shan. Current research situation of the characteristics of recurrent optic neuritis and the pathogenesis of optic neuritis. Chinese Journal of Ocular Fundus Diseases, 2019, 35(3): 295-298. doi: 10.3760/cma.j.issn.1005-1015.2019.03.020 Copy

1.	Falcão-Gonçalves AB, Bichuetti DB, de Oliveira EML. Recurrent optic neuritis as the initial symptom in demyelinating diseases[J]. J Clin Neurol, 2018, 14(3): 351-358. DOI: 10.3988/jcn.2018.14.3.351.
2.	Petzold A, Plant GT. Diagnosis and classification of autoimmune optic neuropathy[J]. Autoimmun Rev, 2014, 13(4-5): 539-545. DOI: 10.1016/j.autrev.2014.01.009.
3.	Kim SM, Kim SJ, Lee HJ, et al. Differential diagnosis of neuromyelitis optica spectrum disorders[J]. Ther Adv Neurol Disord, 2017, 10(7): 265-289. DOI: 10.1177/1756285617709723.
4.	Saini M, Khurana D. Chronic relapsing inflammatory optic neuropathy[J]. Ann Indian Acad Neurol, 2010, 13(1): 61-63. DOI: 10.4103/0972-2327.61280.
5.	Kidd D, Burton B, Plant GT, et al. Chronic relapsing inflammatory optic neuropathy (CRION)[J]. Brain, 2003, 126(Pt 2): 276-284.
6.	Petzold A, Pittock S, Lennon V, et al. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis[J]. J Neurol Neurosurg Psychiatry, 2010, 81(1): 109-111. DOI: 10.1136/jnnp.2008.146894.
7.	Arzani M, Sahraian MA, Rezaei H, et al. Recurrent isolated optic neuritis: a study on 22 patients[J]. Iran J Neurol, 2017, 16(3): 130-135.
8.	Myers TD, Smith JR, Wertheim MS, et al. Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease[J]. Br J Ophthalmol, 2004, 88(5): 673-680. DOI: 10.1136/bjo.2003.028472.
9.	王颖云, 魏世辉, 范珂, 等. 复发性视神经炎54例临床特点及自身免疫抗体的分布[J]. 中国实用眼科杂志, 2013, 31(3): 346-349. DOI: 10.3760/cma.J.issn.1006-4443.2013.03.026.Wang YY, Wei SH, Fan K, et al. Distribution of autoimmune antibodies and clinical features in 54 cases with recurrent optic neuritis[J]. Chin J Pract Ophthalmol, 2013, 31(3): 346-349. DOI: 10.3760/cma.J.issn.1006-4443.2013.03.026.
10.	邓娟, 梁雪梅. 复发型视神经脊髓炎的临床特征与视功能分析[J]. 中华眼底病杂志, 2013, 29(3): 240-244. DOI: 10.3760/cma.j.issn.1005-1015.2013.03.003.Deng J, Liang XM. Clinical features and visuaI funotion of recurrent neuromyelitis optica[J]. Chin J Ocul Fundus Dis, 2013, 29(3): 240-244. DOI: 10.3760/cma.j.issn.1005-1015.2013.03.003.
11.	赵颖, 徐全刚, 魏世辉, 等. 16岁以下的儿童脱髓鞘性视神经炎临床特征分析[J]. 中华眼底病杂志, 2017, 335(5): 472-475. DOI: 10.3760/cma.j.issn.1005-1015.2017.05.008.Zhao Y, Xu QG, Wei SH, et al. Analysis of clinical characteristics of demyelinating optic neuritis in children under the age of 16[J]. Chin J Ocul Fundus Dis, 2017, 335(5): 472-475. DOI: 10.3760/cma.j.issn.1005-1015.2017.05.008.
12.	Moss HE, Gao W, Balcer LJ, et al. Association of race/ethnicity with visual outcomes following acute optic neuritis: an analysis of the Optic Neuritis Treatment Trial[J]. JAMA ophthalmology, 2014, 132(4): 421-427. DOI: 10.1001/jamaophthalmol.2013.7995.
13.	Matiello M, Lennon VA, Jacob A, et al. NMO-IgG predicts the outcome of recurrent optic neuritis[J]. Neurology, 2008, 70(23): 2197-2200. DOI: 10.1212/01.wnl.0000303817.82134.da.
14.	Benoilid A, Tilikete C, Collongues N, et al. Relapsing optic neuritis: a multicentre study of 62 patients[J]. Mult Scler, 2014, 20(7): 848-853. DOI: 10.1177/1352458513510223.
15.	Bertsch-Gout M, Loeb R, Finch AK, et al. High resolution retinal scanning reveals regional structural differences between MS and NMOSD optic neuritis regardless of antibody status[J]. J Neurol Sci, 2018, 384: 61-66. DOI: 10.1016/j.jns.2017.11.017.
16.	Liu Y, You C, Zhang Z, et al. Roles of Treg/Th17 cell imbalance and neuronal damage in the visual dysfunction observed in experimental autoimmune optic neuritis chronologically[J]. Neuromolecular Med, 2015, 17(4): 391-403. DOI: 10.1007/s12017-015-8368-4.
17.	Henderson AP, Altmann DR, Trip SA, et al. Early factors associated with axonal loss after optic neuritis[J]. Ann Neurol, 2011, 70(6): 955-963. DOI: 10.1002/ana.22554.
18.	Lee TH, Ji YS, Park SW, et al. Retinal ganglion cell and axonal loss in optic neuritis: risk factors and visual functions[J]. Eye (Lond), 2017, 31(3): 467-474. DOI: 10.1038/eye.2016.253.
19.	Tian G, Li Z, Zhao G, et al. Evaluation of retinal nerve fiber layer and ganglion cell complex in patients with optic neuritis or neuromyelitis optica spectrum disorders using optical coherence tomography in a Chinese cohort[J/OL]. J Ophthalmol, 2015, 2015: 832784[2015-11-15]. https://dx.doi.org/10.1155/2015/832784. DOI: 10.1155/2015/832784.
20.	Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases[J]. Nature, 2006, 443(7113): 787-795. DOI: 10.1038/nature05292.
21.	刘文冬, 于明依, 姜利斌. 视神经脊髓炎相关视神经炎发病机制及生物学标志物的研究进展[J]. 中华眼科杂志, 2019, 55(3): 228-233. DOI: 10.3760/cma.j.issn.0412-4081.2019.03.015.Liu WD, Yu MY, Jiang LB. The progress of research on the immune pathogenesis and biomarkers in optic neuritis related to neuromyelitis optica[J]. Chin J Ophthalmol, 2019, 55(3): 228-233. DOI: 10.3760/cma.j.issn.0412-4081.2019.03.015.
22.	Larabee CM, Hu Y, Desai S, et al. Myelin-specific Th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in C57BL/6 mice[J]. Mol Vis, 2016, 22: 332-341.
23.	Bettelli E, Pagany M, Weiner HL, et al. Myelin oligodendrocyte glycoproteinspecific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis[J]. J Exp Med, 2003, 197(9): 1073-1081. DOI: 10.1084/jem.20021603.
24.	Patergnani S, Fossati V, Bonora M, et al. Mitochondria in multiple sclerosis: molecular mechanisms of pathogenesis[J]. Int Rev Cell Mol Biol, 2017, 328: 49-103. DOI: 10.1016/bs.ircmb.2016.08.003.
25.	Varhaug KN, Vedeler CA, Tzoulis C, et al. Multiple sclerosis - a mitochondria-mediated disease[J]. Tidsskr Nor Laegeforen, 2017, 137(4): 284-287. DOI: 10.4045/tidsskr.16.0210.
26.	Witte ME, Mahad DJ, Lassmann H, et al. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis[J]. Trends Mol Med, 2014, 20(3): 179-187. DOI: 10.1016/j.molmed.2013.11.007.
27.	Qi X, Lewin AS, Sun L, et al. Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis[J]. Invest Ophthalmol Vis Sci, 2007, 48(2): 681-691. DOI: 10.1167/iovs.06-0553.
28.	Dunham J, van de Vis R, Bauer J, et al. Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey[J/OL]. PLoS One, 2017, 12(11): 0188013[2017-11-14]. http://dx.plos.org/10.1371/journal.pone.0188013. DOI: 10.1371/journal.pone.0188013.
29.	Glenn JD, Xue P, Whartenby KA. Gemcitabine directly inhibits effector CD4 T cell activation and prevents experimental autoimmune encephalomyelitis[J]. J Neuroimmunol, 2018, 316: 7-16. DOI: 10.1016/j.jneuroim.2017.12.002.
30.	Khan RS, Dine K, Geisler JG, et al. Mitochondrial uncoupler prodrug of 2, 4-dinitrophenol, MP201, prevents neuronal damage and preserves vision in experimental optic neuritis[J/OL]. Oxid Med Cell Longev, 2017, 2017: 7180632[2017-06-07]. https://dx.doi.org/10.1155/2017/7180632. DOI: 10.1155/2017/7180632.
31.	Horstmann L, Kuehn S, Pedreiturria X, et al. Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis[J]. J Neuroimmunol, 2016, 298: 32-41. DOI: 10.1016/j.jneuroim.2016.06.008.
32.	Vieira JP, Sequeira J, Brito MJ. Postinfectious anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis and myelitis[J]. J Child Neurol, 2017, 32(12): 996-999. DOI: 10.1177/0883073817724927.
33.	Roemer SF, Parisi JE, Lennon VA, et al. Patternspecific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1194-1205. DOI: 10.1093/brain/awl371.
34.	Rostasy K, Mader S, Schanda K, et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis[J]. Arch Neurol, 2012, 69(6): 752-756. DOI: 10.1001/archneurol.2011.2956.
35.	Johnson DA, Johnson JA. NRF2--a therapeutic target for the treatment of neurodegenerative diseases[J]. Free Radic Biol Med, 2015, 88(Pt B): 253-267. DOI: 10.1016/j.freeradbiomed.2015.07.147.
36.	Larabee CM, Desai S, Agasing A, et al. Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis[J]. Mol Vis, 2016, 22: 1503-1513.
37.	Martin A, Tegla CA, Cudrici CD, et al. Role of SIRT1 in autoimmune demyelination and neurodegeneration[J]. Immunol Res, 2015, 61(3): 187-197. DOI: 10.1007/s12026-014-8557-5.
38.	Khan RS, Dine K, Das Sarma J, et al. SIRT1 activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease[J]. Acta Neuropathol Commun, 2014, 2: 3. DOI: 10.1186/2051-5960-2-3.
39.	Hedstrom AK, Olsson T, Alfredsson L. The role of environment and lifestyle in determining the risk of multiple sclerosis[J]. Curr Top Behav Neurosci, 2015, 26: 87-104. DOI: 10.1007/7854_2015_372.
40.	Eskandarieh S, Nedjat S, Abdollahpour I, et al. Environmental risk factors in neuromyelitis optica spectrum disorder: a case-control study[J]. Acta Neurol Belg, 2018, 118(2): 277-287. DOI: 10.1007/s13760-018-0900-5.

1. Falcão-Gonçalves AB, Bichuetti DB, de Oliveira EML. Recurrent optic neuritis as the initial symptom in demyelinating diseases[J]. J Clin Neurol, 2018, 14(3): 351-358. DOI: 10.3988/jcn.2018.14.3.351.
2. Petzold A, Plant GT. Diagnosis and classification of autoimmune optic neuropathy[J]. Autoimmun Rev, 2014, 13(4-5): 539-545. DOI: 10.1016/j.autrev.2014.01.009.
3. Kim SM, Kim SJ, Lee HJ, et al. Differential diagnosis of neuromyelitis optica spectrum disorders[J]. Ther Adv Neurol Disord, 2017, 10(7): 265-289. DOI: 10.1177/1756285617709723.
4. Saini M, Khurana D. Chronic relapsing inflammatory optic neuropathy[J]. Ann Indian Acad Neurol, 2010, 13(1): 61-63. DOI: 10.4103/0972-2327.61280.
5. Kidd D, Burton B, Plant GT, et al. Chronic relapsing inflammatory optic neuropathy (CRION)[J]. Brain, 2003, 126(Pt 2): 276-284.
6. Petzold A, Pittock S, Lennon V, et al. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis[J]. J Neurol Neurosurg Psychiatry, 2010, 81(1): 109-111. DOI: 10.1136/jnnp.2008.146894.
7. Arzani M, Sahraian MA, Rezaei H, et al. Recurrent isolated optic neuritis: a study on 22 patients[J]. Iran J Neurol, 2017, 16(3): 130-135.
8. Myers TD, Smith JR, Wertheim MS, et al. Use of corticosteroid sparing systemic immunosuppression for treatment of corticosteroid dependent optic neuritis not associated with demyelinating disease[J]. Br J Ophthalmol, 2004, 88(5): 673-680. DOI: 10.1136/bjo.2003.028472.
9. 王颖云, 魏世辉, 范珂, 等. 复发性视神经炎54例临床特点及自身免疫抗体的分布[J]. 中国实用眼科杂志, 2013, 31(3): 346-349. DOI: 10.3760/cma.J.issn.1006-4443.2013.03.026.Wang YY, Wei SH, Fan K, et al. Distribution of autoimmune antibodies and clinical features in 54 cases with recurrent optic neuritis[J]. Chin J Pract Ophthalmol, 2013, 31(3): 346-349. DOI: 10.3760/cma.J.issn.1006-4443.2013.03.026.
10. 邓娟, 梁雪梅. 复发型视神经脊髓炎的临床特征与视功能分析[J]. 中华眼底病杂志, 2013, 29(3): 240-244. DOI: 10.3760/cma.j.issn.1005-1015.2013.03.003.Deng J, Liang XM. Clinical features and visuaI funotion of recurrent neuromyelitis optica[J]. Chin J Ocul Fundus Dis, 2013, 29(3): 240-244. DOI: 10.3760/cma.j.issn.1005-1015.2013.03.003.
11. 赵颖, 徐全刚, 魏世辉, 等. 16岁以下的儿童脱髓鞘性视神经炎临床特征分析[J]. 中华眼底病杂志, 2017, 335(5): 472-475. DOI: 10.3760/cma.j.issn.1005-1015.2017.05.008.Zhao Y, Xu QG, Wei SH, et al. Analysis of clinical characteristics of demyelinating optic neuritis in children under the age of 16[J]. Chin J Ocul Fundus Dis, 2017, 335(5): 472-475. DOI: 10.3760/cma.j.issn.1005-1015.2017.05.008.
12. Moss HE, Gao W, Balcer LJ, et al. Association of race/ethnicity with visual outcomes following acute optic neuritis: an analysis of the Optic Neuritis Treatment Trial[J]. JAMA ophthalmology, 2014, 132(4): 421-427. DOI: 10.1001/jamaophthalmol.2013.7995.
13. Matiello M, Lennon VA, Jacob A, et al. NMO-IgG predicts the outcome of recurrent optic neuritis[J]. Neurology, 2008, 70(23): 2197-2200. DOI: 10.1212/01.wnl.0000303817.82134.da.
14. Benoilid A, Tilikete C, Collongues N, et al. Relapsing optic neuritis: a multicentre study of 62 patients[J]. Mult Scler, 2014, 20(7): 848-853. DOI: 10.1177/1352458513510223.
15. Bertsch-Gout M, Loeb R, Finch AK, et al. High resolution retinal scanning reveals regional structural differences between MS and NMOSD optic neuritis regardless of antibody status[J]. J Neurol Sci, 2018, 384: 61-66. DOI: 10.1016/j.jns.2017.11.017.
16. Liu Y, You C, Zhang Z, et al. Roles of Treg/Th17 cell imbalance and neuronal damage in the visual dysfunction observed in experimental autoimmune optic neuritis chronologically[J]. Neuromolecular Med, 2015, 17(4): 391-403. DOI: 10.1007/s12017-015-8368-4.
17. Henderson AP, Altmann DR, Trip SA, et al. Early factors associated with axonal loss after optic neuritis[J]. Ann Neurol, 2011, 70(6): 955-963. DOI: 10.1002/ana.22554.
18. Lee TH, Ji YS, Park SW, et al. Retinal ganglion cell and axonal loss in optic neuritis: risk factors and visual functions[J]. Eye (Lond), 2017, 31(3): 467-474. DOI: 10.1038/eye.2016.253.
19. Tian G, Li Z, Zhao G, et al. Evaluation of retinal nerve fiber layer and ganglion cell complex in patients with optic neuritis or neuromyelitis optica spectrum disorders using optical coherence tomography in a Chinese cohort[J/OL]. J Ophthalmol, 2015, 2015: 832784[2015-11-15]. https://dx.doi.org/10.1155/2015/832784. DOI: 10.1155/2015/832784.
20. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases[J]. Nature, 2006, 443(7113): 787-795. DOI: 10.1038/nature05292.
21. 刘文冬, 于明依, 姜利斌. 视神经脊髓炎相关视神经炎发病机制及生物学标志物的研究进展[J]. 中华眼科杂志, 2019, 55(3): 228-233. DOI: 10.3760/cma.j.issn.0412-4081.2019.03.015.Liu WD, Yu MY, Jiang LB. The progress of research on the immune pathogenesis and biomarkers in optic neuritis related to neuromyelitis optica[J]. Chin J Ophthalmol, 2019, 55(3): 228-233. DOI: 10.3760/cma.j.issn.0412-4081.2019.03.015.
22. Larabee CM, Hu Y, Desai S, et al. Myelin-specific Th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in C57BL/6 mice[J]. Mol Vis, 2016, 22: 332-341.
23. Bettelli E, Pagany M, Weiner HL, et al. Myelin oligodendrocyte glycoproteinspecific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis[J]. J Exp Med, 2003, 197(9): 1073-1081. DOI: 10.1084/jem.20021603.
24. Patergnani S, Fossati V, Bonora M, et al. Mitochondria in multiple sclerosis: molecular mechanisms of pathogenesis[J]. Int Rev Cell Mol Biol, 2017, 328: 49-103. DOI: 10.1016/bs.ircmb.2016.08.003.
25. Varhaug KN, Vedeler CA, Tzoulis C, et al. Multiple sclerosis - a mitochondria-mediated disease[J]. Tidsskr Nor Laegeforen, 2017, 137(4): 284-287. DOI: 10.4045/tidsskr.16.0210.
26. Witte ME, Mahad DJ, Lassmann H, et al. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis[J]. Trends Mol Med, 2014, 20(3): 179-187. DOI: 10.1016/j.molmed.2013.11.007.
27. Qi X, Lewin AS, Sun L, et al. Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis[J]. Invest Ophthalmol Vis Sci, 2007, 48(2): 681-691. DOI: 10.1167/iovs.06-0553.
28. Dunham J, van de Vis R, Bauer J, et al. Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey[J/OL]. PLoS One, 2017, 12(11): 0188013[2017-11-14]. http://dx.plos.org/10.1371/journal.pone.0188013. DOI: 10.1371/journal.pone.0188013.
29. Glenn JD, Xue P, Whartenby KA. Gemcitabine directly inhibits effector CD4 T cell activation and prevents experimental autoimmune encephalomyelitis[J]. J Neuroimmunol, 2018, 316: 7-16. DOI: 10.1016/j.jneuroim.2017.12.002.
30. Khan RS, Dine K, Geisler JG, et al. Mitochondrial uncoupler prodrug of 2, 4-dinitrophenol, MP201, prevents neuronal damage and preserves vision in experimental optic neuritis[J/OL]. Oxid Med Cell Longev, 2017, 2017: 7180632[2017-06-07]. https://dx.doi.org/10.1155/2017/7180632. DOI: 10.1155/2017/7180632.
31. Horstmann L, Kuehn S, Pedreiturria X, et al. Microglia response in retina and optic nerve in chronic experimental autoimmune encephalomyelitis[J]. J Neuroimmunol, 2016, 298: 32-41. DOI: 10.1016/j.jneuroim.2016.06.008.
32. Vieira JP, Sequeira J, Brito MJ. Postinfectious anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis and myelitis[J]. J Child Neurol, 2017, 32(12): 996-999. DOI: 10.1177/0883073817724927.
33. Roemer SF, Parisi JE, Lennon VA, et al. Patternspecific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis[J]. Brain, 2007, 130(Pt 5): 1194-1205. DOI: 10.1093/brain/awl371.
34. Rostasy K, Mader S, Schanda K, et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis[J]. Arch Neurol, 2012, 69(6): 752-756. DOI: 10.1001/archneurol.2011.2956.
35. Johnson DA, Johnson JA. NRF2--a therapeutic target for the treatment of neurodegenerative diseases[J]. Free Radic Biol Med, 2015, 88(Pt B): 253-267. DOI: 10.1016/j.freeradbiomed.2015.07.147.
36. Larabee CM, Desai S, Agasing A, et al. Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis[J]. Mol Vis, 2016, 22: 1503-1513.
37. Martin A, Tegla CA, Cudrici CD, et al. Role of SIRT1 in autoimmune demyelination and neurodegeneration[J]. Immunol Res, 2015, 61(3): 187-197. DOI: 10.1007/s12026-014-8557-5.
38. Khan RS, Dine K, Das Sarma J, et al. SIRT1 activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease[J]. Acta Neuropathol Commun, 2014, 2: 3. DOI: 10.1186/2051-5960-2-3.
39. Hedstrom AK, Olsson T, Alfredsson L. The role of environment and lifestyle in determining the risk of multiple sclerosis[J]. Curr Top Behav Neurosci, 2015, 26: 87-104. DOI: 10.1007/7854_2015_372.
40. Eskandarieh S, Nedjat S, Abdollahpour I, et al. Environmental risk factors in neuromyelitis optica spectrum disorder: a case-control study[J]. Acta Neurol Belg, 2018, 118(2): 277-287. DOI: 10.1007/s13760-018-0900-5.

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Current research situation of the characteristics of recurrent optic neuritis and the pathogenesis of optic neuritis

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