臨床眼科69巻4号

2015年04月発行

連載 今月の話題

多発性硬化症と視神経脊髄炎の視神経炎—診断と治療の新たな展開

著者： 中尾雄三¹

所属機関： ¹近畿大学医学部眼科

ページ範囲：P.427 - P.434

　多発性硬化症と視神経脊髄炎の視神経炎はその免疫システムが全く異なるため病理・病態に差があり，正しい診断と効果的な治療を行うにはその事実に沿った配慮が必要である。最新の情報として，診断と検査ではOCT検査による多発性硬化症（MS）と視神経脊髄炎（NMO）の病態の把握，抗MOG抗体とSema4Aの臨床の意義について，治療では急性発症期の免疫グロブリン大量静注療法（IVIG），慢性寛解期のフィンゴリモド・ナタリズマブ・トシリズマブ治療について解説する。

参考文献

1）糸山泰人：内科100年のあゆみ（神経）・多発性硬化症．日本内科学会雑誌　91：2339-2343，2002

2）Lennon VA, Wingerchuk DM, Kryzer TJ：A serum autoantibody marker of neuromyelitis optica：distinction from multiple sclerosis. Lancet　364：2106-2112, 2004

3）Lennon VA, Kryzer TJ, Pittock SJ et al：IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med　202：473-477, 2005

4）Wingerchuk DM, Lennon VA, Pittock SJ et al：Revised diagnostic criteria for neuromyelitis optica. Neurology　66：1485-1489, 2006

5）中尾雄三・山本　肇・有村英子・他：抗アクアポリン4抗体陽性視神経炎の臨床的特徴．神経眼科　25：327-342，2008

6）Kanamori A, Nakamura M, Yamada Y et al：Longotudinal study of retinal nerve fiber layer thickness and ganglion cell complex in traumatic optic neuropathy. Arch Ophthalmol　130：1067-1069, 2012

7）三須建郎，藤原一男，糸山泰人：NMOとアクアポリン4の病理的意義．Clinical Neuroscience　26：770-773，2008

8）Costello F, Coupland S, Hodge W et al：Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol　59：963-969, 2006

9）Merle H, Olindo S, Donnino A et al：Retinal peripapillary nerve fiber layer thickness in optic neuropathies. Inv Ophthalmol Vis Sci　49：4412-4444, 2008

10）Fisher JB, Jacobs DA, Markowitz CE et al：Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology　113：324-332, 2006

11）Naismith RT, Tulman NT, Xu J et al：Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology　72：1077-1082, 2009

12）Monterio ML, Femandes DB, Apostolos-Pereira SL et al：Quantification of retinal neural loss in patients neuromyelitis optica and multiple sclerosis with or without optic neuritis using Fourier-damain optical coherence tomography. Invest Ophthalmol Vis Sci　26：3959-3966, 2012

13）Pueyo V, Martin J, Fernandez J et al：Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis. Mult Scler　14：609-614, 2008

14）Talman LS, Bisker ER, Sackel DJ et al：Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Ann Neurol　67：749-760, 2010

evaluation of retinal neurodegeneration in patients with multiple sclerosis. Plos One　7：e30922, 2012

16）Gabilondo I, Martinez-Lapiscina EH, Martinez-Heras E et al：Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann Neurol　75：98-107, 2014

17）Di Maggio G, Santangelo R, Guerrieri S et al：Optical coherence tomography and visual evoked potentials：Which is more sensitive in multiple sclerosis. Mult Scler　20：1342-1347, 2014

18）Garcin-Martin E, Polo V, Larrosa JM et al：Retinal layer segmentation in patients with multiple sclelosis using spectral domain optical coherence tomography. Ophthalmology　121：573-579, 2014

19）Balk L, Tewarie P, Killestein J et al：Disease course heterogeneiety and OCT in multiple sclerosis. Mult Scler　20：1198-1206, 2014

20）Young KL, Brandt AU, Petzold A et al：Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis. Eur J Neurol　20：803-811, 2013

identification of morphologic retinal abnormalities in neuromyelitis optica. Neurology　80：1406-1414, 2013

22）Gelfand JM, Nolan R, Schwartz DM et al：Microcystic macular oedema in multiple sclerosis is associated with disease severity. Brain　135：1786-1793, 2012

23）Saidha S, SotirchosES, Ibrahim MA et al：Microcystic macular oedema, thickness inner nuclear layer of the retina, and disease characteristics in multiple sclerosis：a retrospective study. Lancet Neurol　11：963-972, 2012

24）Srivastava R, Aslam M, Kalluri SR et al：Potassium channel KIR4.1as an immune target in multiple sclerosis. N Engl J Med　367：115-123, 2012

identification of morphologic retinal abnormalities in neuromyelitis optica. Neurology　80：1406-1414, 2013

26）Abegg M, Dysli M, Wolf S：Microcystic macular oedema：retrograde maculopathy caused by optic neuropathy. Ophthalmology　121：142-149, 2014

27）Kezuka T, Usui Y, Yamakawa N, et al：Relationship between NMO-antibody and anti-MOG antibody in optic neuritis. J Neuroophthalmol　32：107-110, 2012

28）Sato DK, Callegaro D, Lana-Peixoto MA et al：Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology　82：474-481, 2014

29）Kitley J, Waters P, Woodhall M et al：Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies. JAMA Neurol　71：276-283, 2014

30）Nakatsuji Y, Okuno T, Moriya M et al：Elevation of sema4A implicates Th cell skewing and the efficacy of IFN-Jβtherapy in multiple sclerosis. Immunol　188：4858-4865, 2012

31）Ruprecht K, Klinker E, Dintelmann T et al：Plasma exchange for severe optic neuritis, treatment of 10 patients. Neurology　63：1081-1083, 2004

32）Feasby T, Banwell B, Benstead T et al：Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev　21（suppl1）：S57-S107, 2007

33）Buttmann M, Kaveri S, Hartung HP：Polyclonal immunoglobulin G for autoimmune demyelinating nervous system disorders. Trend in Pharm Sci　34：445-456, 2013

34）Lucchnetti CF, Mandler RN, McGavern D et al：A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica. Brain　125：1450-1461, 2002

35）Sorensen PS：The role of intravenous immunoglobulin in the treatment of multiple sclerosis. J Neurol Sci　206：123-130, 2003

36）Wingerchuk DM：Neuromyelitis optica：potential roles for intravenous immunoglobulin. J Clin Immunol　33：S33-S37, 2013

37）Curró Dossi B, Amadori A, Cirafisi C et al：New therapeutic perspective for demyelinating retrobulbar optic neuritis. Ital J Neurol Sci　19：45-48, 1998

38）Tselis A, J. Peruma J, Caon C et al：Treatment of corticosteroid refractory optic neuritis in multiple sclerosis patients with intravenous immunoglobulin. Eur J Neurol　15：1163-1167, 2008

39）Spalice A, Properzi E, Lo Faro V et al：Intravenous immunoglobulin and interferon：successful treatment of optic neuritis in pediatric multiple sclerosis. J Child Neurol　19：623-626, 2004

40）Roed HG, Langkilde A, Sellebjerg F et al：A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis. Neurology　64：804-810, 2005

41）中尾雄三・中村雄作・青松圭一・他：ステロイド治療が無効な抗Aquaporin4抗体陽性視神経炎に対する免疫グロブリン大量静注療法．神経眼科　29：424-433，2012

42）Achiron A：Winning combination：the additive/synergic benefits of IVIG in corticosteroid refractory optic neuritis. Eur J Neurol　15：1145, 2008

43）Nakamura M, Nakazawa T, Doi H et al：Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica. Graefes Arch Clin Exp Ophthalmol　248：1777-1785, 2010

44）NoseworthyJH, Obrien PC, Petterson TM et al：A randomized trial of intravenous immunoglobulin inflammatory demyelinating optic neuritis. Neurology　56：1514-1522, 2001

45）Guy J, Mancuso A, Quisling RG et al：Gadolinium-DTPA-enhanced magnetic resonance imaging in optic neuropathies. Ophthalmology　97：592-599, 1990

46）中尾雄三：MS/NMOと視神経炎の新しい展開．神経免疫　17：177-184，2009

47）坪井昌彦・川上　純・江口勝美・他：免疫グロブリン大量点滴療法．最新医学　53：771-779，1998

48）Farcas P, Avnun L, Frisher S et al：Efficacy of repeated IVIg in severe unresponsive GBS. Lancet　350：1747, 1997

49）Taniguchi M, Tsurukisawa N, Higashi N et al：Treatment for Churg-Strauss syndrome：Induction of remission and efficacy of intravenous immunoglobulin therapy. Allergol Int　56：97-103, 2007

50）Kappos L, Radue EW, O'Connor P et al：A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med　362：387-401, 2010

51）Cohen JA, Barkhof F, Comi G et al：Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med　362：402-415, 2010

52）Saida T, Kikuchi S, Itoyama Y：A randomized, controlled trial of fingolimod（FTY720）in Japanese patients with multiple sclerosis. Mult Scler　18：1269-1277, 2012

53）Miller DH, Khan OA, Sheremata WA et al：A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med　348：15-23, 2003

54）Havrdova E, Galetta S, Hutchinson M et al：Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis：a retrospective analysis of the natalizumab safety and efficacy in relapsing-remitting Multiple Sclerosis（AFFIRM）study. Lancet Neurol　8：254-260, 2009

55）Langer-Gould A, Atlas SW, Green AJ et al：Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med　353：375-381, 2005

56）Bloomgren G, Richman S, Hotermans C et al：Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med　366：1870-1880, 2012

57）Chihara N, Aranami T, Sato W et al：Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proc Natl Acad Sci USA　108：3701-3706, 2011

58）Araki M, Aranami T, Matsuoka T et al：Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab. Mod Rheumatol　23：827-831, 2013

59）抗アクアポリン4抗体陽性視神経炎診療ガイドライン作成委員会：抗アクアポリン4抗体陽性視神経炎診療ガイドライン．日眼会誌　118：446-460，2014

60）中尾雄三：眼科診療指針のパラダイムシフト．多発性硬化症と抗アクアポリン4抗体陽性視神経炎．眼科　56：298-304，2014