A Study on the Pathogenesis and Therapy of Optic-Spinal Multiple Sclerosis

视神经脊髓多发性硬化症的发病机制及治疗研究

• 批准号: 17390250
• 负责人: ITOYAMA Yasuto
• 金额: $ 9.09万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390250/
• 关键词: Multiple Sclerosis; Demyelinating disease; Optic-spinal MS; Conventional MS; Neuromyelitis optica; Anti-aquaporin-4 antibody

In Japan, multiple sclerosis (MS) has been classified into two subtypes, 1) conventional MS (CMS) in which demyelinating lesions are disseminated in the central nervous system and 2) optic-spinal MS (OSMS) characterized by the selective involvement of the optic nerves and spinal cord. OSMS and Neuromyelitis optica (NMO) have many features in common. We investigated the pathogeneses and therapy of OSMS :1. Features of NMO-IgG-positive casesIn 2004, we reported an NMO-OSMS-specific autoantibody, NMO-IgG. Longitudinally extensive. spinal cord lesions and blindness are commonly seen in NMO-IgG-positive patients. Also, some of them have unique brain lesions, such as longitudinally extensive lesions and periaqueductal lesions.2. Establishment of a sensitive assay of anti-aquaporin-4 (AQP4) antibodyThe target antigen of NMO-IgG was identified as AQP4 in 2005. We established a sensitive assay of anti-AQP4 antibody and found that about 90% of patients with NMO and the high-risk syndrome were seropositive, but none of the patients with MS and other diseases were positive for this autoantibody, suggesting that NMO is associated with anti-AQP4 antibody.3. Loss of AQP4 in NMO lesionsWe did a comparative neuropathological study of the spinal cord lesions of NMO and CMS. As a result, we found that in NMO AQP4 was completely lost in the perivascular regions where immunoglobulins and activated complements were deposited. The immunoreactivity of myelin basic protein was rather preserved. In contrast, AQP4 was upregulated in the demyelinating lesions of MS. These findings suggest that AQP4 densely expressed on the foot processes of astrocytes are targeted in NMO and that NMO is a distinct clinical entity from MS.4. Therapy of NMOWe found that half of NMO patients who were refractory to high-dose IV methylprednisolone did respond to plasma exchange. We also found that long-term low-dose corticosteroid was effective to reduce relapses in NMO

在日本，多发性硬化症（MS）被分为两种亚型：1)常规多发性硬化症（CMS），脱髓鞘病变弥散在中枢神经系统；2)视神经-脊髓多发性硬化症（OSMS），以选择性累及视神经和脊髓为特征。OSMS和视神经脊髓炎（NMO）有许多共同的特征。我们探讨了OSMS的发病机制和治疗方法：1。2004年，我们报道了一种nmo - osm特异性自身抗体NMO-IgG。纵向广泛。脊髓损伤和失明常见于nmo - igg阳性患者。此外，其中一些有独特的脑病变，如纵向广泛病变和导水管周围病变。抗水通道蛋白-4 （AQP4）抗体灵敏检测方法的建立2005年确定NMO-IgG的靶抗原为AQP4。我们建立了抗aqp4抗体的灵敏检测方法，发现NMO及高危综合征患者中约90%血清抗体阳性，而MS及其他疾病患者均无此自身抗体阳性，提示NMO与抗aqp4抗体相关。我们对NMO和CMS脊髓病变进行了神经病理学对比研究。结果，我们发现在NMO中，AQP4在免疫球蛋白和活化补体沉积的血管周围区域完全丢失。髓鞘碱性蛋白的免疫反应性较好。相反，AQP4在ms脱髓鞘病变中表达上调。这些发现表明，在星形胶质细胞足突上密集表达的AQP4是NMO的靶点，NMO与ms - 4是一个不同的临床实体。NMO的治疗我们发现，半数对大剂量静脉注射甲基强的松龙难治性NMO患者对血浆置换有反应。我们还发现，长期低剂量皮质类固醇可有效减少NMO的复发

项目成果

Painful tonic seizure

痛苦的强直性癫痫发作

• 发表时间: 2007
• 期刊: 脊椎脊髄ジャーナル (印刷中)
• 作者: 岩本 禎彦;宇津見 七海;近江 俊徳;後藤 孝也;坂本 敦司;中山 一大;中山 一大;中山 一大;岩本 禎彦;後藤 孝也;坂本 敦司;北村 歌奈子;近江 俊徳;近江 俊徳;ルバグワスレン・ムンフトルガ;Watanabe S;Miyazawa I;Watanabe S;Nakamura M;Nakashima I;Nakashima I;Nakamura M;Watanabe S;Misu T;Takahashi T;中島一郎;渡部承平
• 通讯作者: 渡部承平

視神経脊髄型多発性硬化症

视神经脊髓多发性硬化症

• 发表时间: 2006
• 期刊: 神経研究の進歩 50
• 作者: Huqun.;et al.;西山修平;Banno H et al.;Ogura Y. et al.;中村正史;Katsuno M et al.;Fujiwara T. et al.;佐藤 滋;Jiang Y et al.;Nukiwa M. et al.;藤原一男
• 通讯作者: 藤原一男

A comparative neuropathological analysis of Japanese cases of neuromyelitis optical and multiple sclerosis

日本视神经脊髓炎和多发性硬化症病例的神经病理学比较分析

• 发表时间: 2005
• 期刊: Neurology 64(suppl 1)
• 作者: Fujihara K;Misu T;Narikawa K;Nakashima I;Sato S;Itoyama Y.;Nakashima I;Narikawa K;Misu T
• 通讯作者: Misu T

Medimond

梅迪蒙德

• 期刊: Current Topics in Neuroimmunology (In press)
• 作者: Fujihara K;Misu T;Narikawa K;Nakashima I;Sato S;Itoyama Y.;Nakashima I;Narikawa K;Misu T;Narikawa K;Narikawa K;Nakashima I;Watanabe S;Osoegawa N;Nakamura M;Nakashima I;Watanabe S;Watanabe S;Nakamura M;Nakashima I;Nakashima I;Nakamura M;Watanabe S;Misu T;Takahashi T;Fujihara K
• 通讯作者: Fujihara K

神経救急・集中治療ハンドブック

神经急诊/重症监护手册

• 发表时间: 2006
• 作者: Fujihara K.Multiple Sclerosis.Ed by Moriya H;Homan M;Uchida A;Hagino T;Kurosaka M;Toyama Fujihara K.Multiple Sclerosis.Ed by Moriya H;Homan M;Uchida A;Hagino T;Kurosaka M;Toyama Y;高橋利幸
• 通讯作者: 高橋利幸