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Yoshiki Takai

Section

Tohoku University Hospital

Job title

Assistant Professor

Degree

博士（医学）（東北大学）

researchmap

https://researchmap.jp/y-takai_research

J-GLOBAL ID

201901008223402530

Research Areas 1

Life sciences / Neurology /

Papers 128

Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders. International-journal

Yoshiki Takai, Tatsuro Misu, Hiroyoshi Suzuki, Toshiyuki Takahashi, Hiromi Okada, Shinya Tanaka, Kenji Okita, Shunichi Sasou, Mika Watanabe, Chihiro Namatame, Yuki Matsumoto, Hirohiko Ono, Kimihiko Kaneko, Shuhei Nishiyama, Hiroshi Kuroda, Ichiro Nakashima, Hans Lassmann, Kazuo Fujihara, Yasuto Itoyama, Masashi Aoki

Brain : a journal of neurology　144　(8)　2401-2415　2021/03/12

DOI： 10.1093/brain/awab102 　

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Aquaporin 4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) is an autoimmune astrocytopathic disease pathologically characterized by the massive destruction and regeneration of astrocytes with diverse types of tissue injury with or without complement deposition. However, it is unknown whether this diversity is derived from differences in pathological processes or temporal changes. Furthermore, unlike for the demyelinating lesions in multiple sclerosis, there has been no staging of astrocytopathy in AQP4-IgG+NMOSD based on astrocyte morphology. Therefore, we classified astrocytopathy of the disease by comparing the characteristic features, such as AQP4 loss, inflammatory cell infiltration, complement deposition and demyelination activity, with the clinical phase. We performed histopathological analyses in eight autopsied cases of AQP4-IgG+NMOSD. There were six women and two men, with a median age of 56.5 years (range, 46-71 years) and a median disease duration of 62.5 months (range, 0.6-252 months). Astrocytopathy in AQP4-IgG+NMOSD was classified into the following four stages defined by the astrocyte morphology and immunoreactivity for glial fibrillary acidic protein (GFAP): (a) astrocyte lysis: Extensive loss of astrocytes with fragmented and/or dust-like particles; (b) progenitor recruitment: Loss of astrocytes except small nucleated cells with GFAP-positive fibre-forming foot processes; (c) protoplasmic gliosis: Presence of star-shaped astrocytes with abundant GFAP-reactive cytoplasm; and (d) fibrous gliosis: Lesions composed of densely packed mature astrocytes. The astrocyte lysis and progenitor recruitment stages dominated in clinically acute cases (within 2 months after the last recurrence). Findings common to both stages were the loss of AQP4, a decreased number of oligodendrocytes, the selective loss of myelin-associated glycoprotein and active demyelination with phagocytic macrophages. The infiltration of polymorphonuclear cells and T cells (CD4-dominant) and the deposition of activated complement (C9neo), which reflects the membrane attack complex, a hallmark of acute NMOSD lesions, were selectively observed in the astrocyte lysis stage (98.4% in astrocyte lysis, 1.6% in progenitor recruitment, and 0% in protoplasmic gliosis and fibrous gliosis). Although most of the protoplasmic gliosis and fibrous gliosis lesions were accompanied by inactive demyelinated lesions with a low amount of inflammatory cell infiltration, the deposition of complement degradation product (C3d) was observed in all four stages, even in fibrous gliosis lesions, suggesting the past or chronic occurrence of complement activation, which is a useful finding to distinguish chronic lesions in NMOSD from those in multiple sclerosis. Our staging of astrocytopathy is expected to be useful for understanding the unique temporal pathology of AQP4-IgG+NMOSD.
Myelin oligodendrocyte glycoprotein antibody-associated disease: an immunopathological study International-journal Peer-reviewed

Yoshiki Takai, Tatsuro Misu, Kimihiko Kaneko, Norio Chihara, Koichi Narikawa, Satoko Tsuchida, Hiroya Nishida, Takashi Komori, Morinobu Seki, Teppei Komatsu, Kiyotaka Nakamagoe, Toshimasa Ikeda, Mari Yoshida, Toshiyuki Takahashi, Hirohiko Ono, Shuhei Nishiyama, Hiroshi Kuroda, Ichiro Nakashima, Hiroyoshi Suzuki, Monika Bradl, Hans Lassmann, Kazuo Fujihara, Masashi Aoki

BRAIN　143　(5)　1431-1446　2020/05

DOI： 10.1093/brain/awaa102 　

ISSN： 0006-8950

eISSN： 1460-2156
The real-world impact of biologics for NMOSD: A retrospective single-center study compared with natural course and conventional treatments in Japanese

Naoya Yamazaki, Tatsuro Misu, Yuki Matsumoto, Yoshiki Takai, Chihiro Namatame, Hirohiko Ono, Kimihiko Kaneko, Shuhei Nishiyama, Hiroshi Kuroda, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

Multiple Sclerosis and Related Disorders　92　106176-106176　2024/12
Publisher: Elsevier BV
DOI： 10.1016/j.msard.2024.106176 　

ISSN： 2211-0348
Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD. International-journal

Kimihiko Kaneko, Hiroshi Kuroda, Yuki Matsumoto, Naohiro Sakamoto, Naoya Yamazaki, Naoki Yamamoto, Shu Umezawa, Chihiro Namatame, Hirohiko Ono, Yoshiki Takai, Toshiyuki Takahashi, Juichi Fujimori, Ichiro Nakashima, Yasuo Harigaya, Hans Lassmann, Kazuo Fujihara, Tatsuro Misu, Masashi Aoki

Neurology(R) neuroimmunology & neuroinflammation　11　(5)　e200293　2024/09

DOI： 10.1212/NXI.0000000000200293 　

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OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.
Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder. International-journal

Chihiro Namatame, Yoichiro Abe, Yoshiki Miyasaka, Yoshiki Takai, Yuki Matsumoto, Toshiyuki Takahashi, Tomoji Mashimo, Tatsuro Misu, Kazuo Fujihara, Masato Yasui, Masashi Aoki

International journal of molecular sciences　25　(15)　2024/07/26

DOI： 10.3390/ijms25158169 　

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Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between the human and rodent aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that the humanization of AQP4 ECDs would make the rodent model lesions closer to human NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated using genome-editing technology, and the human AQP4-specific monoclonal antibody (mAb) or six patient-derived IgGs were introduced intraperitoneally into hAQP4 rats and wild-type Lewis (WT) rats after immunization with myelin basic protein and complete Freund's adjuvant. Human AQP4-specific mAb induced astrocyte loss lesions specifically in hAQP4 rats. The patient-derived IgGs also induced NMOSD-like tissue-destructive lesions with AQP4 loss, demyelination, axonal swelling, complement deposition, and marked neutrophil and macrophage/microglia infiltration in hAQP4 rats; however, the difference in AQP4 loss lesion size and infiltrating cells was not significant between hAQP4 and WT rats. The patient-derived IgGs bound to both human and rat AQP4 M23, suggesting their binding to the shared region of human and rat AQP4 ECDs. Anti-AQP4 titers positively correlated with AQP4 loss lesion size and neutrophil and macrophage/microglia infiltration. Considering that patient-derived IgGs vary in binding sites and affinities and some of them may not bind to rodent AQP4, our hAQP4 rat is expected to reproduce NMOSD-like pathology more accurately than WT rats.
Dynamic changes in patient admission and their disabilities in multiple sclerosis and neuromyelitis optica: A Japanese nationwide administrative data study

Yuki Matsumoto, Kunio Tarasawa, Tatsuro Misu, Chihiro Namatame, Yoshiki Takai, Hiroshi Kuroda, Kazuo Fujihara, Kiyohide Fushimi, Kenji Fujimori, Masashi Aoki

Multiple Sclerosis and Related Disorders　81　105349-105349　2024/01
Publisher: Elsevier BV
DOI： 10.1016/j.msard.2023.105349 　

ISSN： 2211-0348
Myelin oligodendrocyte glycoprotein antibody‐associated disorders: An overview

Tatsuro Misu, Yuki Matsumoto, Kimihiko Kaneko, Toshiyuki Takahashi, Yoshiki Takai, Hirohiko Ono, Chihiro Namatame, Shuhei Nishiyama, Juichi Fujimori, Hiroshi Kuroda, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

Clinical and Experimental Neuroimmunology　2023/12/19
Publisher: Wiley
DOI： 10.1111/cen3.12771 　

ISSN： 1759-1961

eISSN： 1759-1961

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Abstract In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders.
MOGAD急性期髄液における活性化補体の解析

金子仁彦, 黒田宙, 小野紘彦, 松本勇貴, 阪本直広, 山崎直也, 山本尚輝, 梅澤周, 生田目知尋, 高井良樹, 高橋利幸, 藤盛寿一, 中島一郎, 藤原一男, 三須建郎, 青木正志

神経免疫学　28　(1)　200-200　2023/09
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
MOGAD急性期髄液における活性化補体の解析

金子仁彦, 黒田宙, 小野紘彦, 松本勇貴, 阪本直広, 山崎直也, 山本尚輝, 梅澤周, 生田目知尋, 高井良樹, 高橋利幸, 藤盛寿一, 中島一郎, 藤原一男, 三須建郎, 青木正志

神経免疫学　28　(1)　200-200　2023/09
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
White blood cell count profiles in anti-aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder and anti-myelin oligodendrocyte glycoprotein antibody-associated disease. International-journal

Tetsuya Akaishi, Tatsuro Misu, Kazuo Fujihara, Kumi Nakaya, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Fumi Itabashi, Ikumi Kanno, Kimihiko Kaneko, Toshiyuki Takahashi, Juichi Fujimori, Yoshiki Takai, Shuhei Nishiyama, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima, Atsushi Hozawa

Scientific reports　13　(1)　6481-6481　2023/04/20

DOI： 10.1038/s41598-023-33827-3 　

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White blood cell (WBC) count profiles in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are still unknown. This study evaluated the total WBC count, differential WBC counts, monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) in patients with these diseases within three months from an attack before acute treatment or relapse prevention and compared the profiles with those in matched volunteers or in multiple sclerosis (MS) patients. AQP4-NMOSD patients (n = 13) had a higher neutrophil count (p = 0.0247), monocyte count (p = 0.0359), MLR (p = 0.0004), and NLR (p = 0.0037) and lower eosinophil (p = 0.0111) and basophil (p = 0.0283) counts than those of AQP4-NMOSD-matched volunteers (n = 65). Moreover, patients with MOGAD (n = 26) had a higher overall WBC count (p = 0.0001), neutrophil count (p < 0.0001), monocyte count (p = 0.0191), MLR (p = 0.0320), and NLR (p = 0.0002) than those of MOGAD-matched volunteers (n = 130). The three demyelinating diseases showed similar levels of the total and differential WBC counts; however, MOGAD and MS showed different structures in the hierarchical clustering and distributions on a two-dimensional canonical plot using differential WBC counts from the other three groups. WBC count profiles were similar in patients with MOGAD and MS but differed from profiles in matched volunteers or patients with AQP4-NMOSD.
Diagnostic implications of MOG-IgG detection in sera and cerebrospinal fluids. International-journal

Yuki Matsumoto, Kimihiko Kaneko, Toshiyuki Takahashi, Yoshiki Takai, Chihiro Namatame, Hiroshi Kuroda, Tatsuro Misu, Kazuo Fujihara, Masashi Aoki

Brain : a journal of neurology　146　(9)　3938-3948　2023/04/15

DOI： 10.1093/brain/awad122 　

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The spectrum of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE), and aquaporin-4-IgG (AQP4-IgG)-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF) and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial two-fold dilutions to determine endpoint titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relations between MOG-IgGSERUM, MOG-IgGCSF, and the phenotypes with multivariable regression. A total of 671 patients were tested (405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD, and 119 with other neurological diseases [OND]) before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15, and Others 11), 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5, and Others 4), and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0, and Others 7) cases. None of AQP4-IgG-positive NMOSD, multiple sclerosis, or OND cases tested positive for MOG-IgGSERUM but two with multiple sclerosis were MOG-IgGCSF-positive; the specificity of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% (95%CI 99%-100%) and 99% (97%-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM were associated with ON and ADEM, whereas MOG-IgGCSF were associated with ADEM and CE. The number needed to test (NNT) of MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY, and 6.1 for Others). In the status of MOG-IgGSERUM/CSF, most cases were double-positive, while including either serum-restricted (13%) or CSF-restricted (17%). These statuses were independently associated with clinical phenotypes, especially with ON in serum and CE in CSF, suggesting these pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted for the clinical and pathological significance of compartmentalized MOG-IgG.
Paths to hippocampal damage in neuromyelitis optica spectrum disorders

Mona Zakani, Magdalini Nigritinou, Markus Ponleitner, Yoshiki Takai, Daniel Hofmann, Sophie Hillebrand, Romana Höftberger, Jan Bauer, Balint Lasztoczi, Tatsuro Misu, Gregor Kasprian, Paulus Rommer, Monika Bradl

Neuropathology and Applied Neurobiology　49　(2)　2023/03/06
Publisher: Wiley
DOI： 10.1111/nan.12893 　

ISSN： 0305-1846

eISSN： 1365-2990
Pathology of myelin oligodendrocyte glycoprotein antibody-associated disease: a comparison with multiple sclerosis and aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders. International-journal

Yoshiki Takai, Tatsuro Misu, Kazuo Fujihara, Masashi Aoki

Frontiers in neurology　14　1209749-1209749　2023

DOI： 10.3389/fneur.2023.1209749 　

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Myelin oligodendrocyte glycoprotein (MOG) is expressed on the outermost layer of the myelin sheath in the central nervous system. Recently, the clinical concept of MOG antibody-associated disease (MOGAD) was established based on the results of human MOG-transfected cell-based assays which can detect conformation-sensitive antibodies against MOG. In this review, we summarized the pathological findings of MOGAD and discussed the issues that remain unresolved. MOGAD pathology is principally inflammatory demyelination without astrocyte destruction, characterized by perivenous demyelination previously reported in acute disseminated encephalomyelitis and by its fusion pattern localized in both the white and gray matter, but not by radially expanding confluent demyelination typically seen in multiple sclerosis (MS). Some of demyelinating lesions in MOGAD show severe loss of MOG staining compared with those of other myelin proteins, suggesting a MOG-targeted pathology in the disease. Perivascular cuffings mainly consist of macrophages and T cells with CD4-dominancy, which is also different from CD8+ T-cell-dominant inflammation in MS. Compared to aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders (NMOSD), perivenous complement deposition is less common, but can be seen on myelinated fibers and on myelin degradation products within macrophages, resembling MS Pattern II pathology. Thus, the pathogenetic contribution of complements in MOGAD is still debatable. Together, these pathological features in MOGAD are clearly different from those of MS and AQP4 antibody-positive NMOSD, suggesting that MOGAD is an independent autoimmune demyelinating disease entity. Further research is needed to clarify the exact pathomechanisms of demyelination and how the pathophysiology relates to the clinical phenotype and symptoms leading to disability in MOGAD patients.
Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With False-Positive Results in SARS-CoV-2 Antigen Tests: A Case Report. International-journal

Naoki Yamamoto, Hajime Ikenouchi, Yoshiki Takai, Kaoru Endo, Masashi Aoki

Cureus　14　(11)　e31514　2022/11

DOI： 10.7759/cureus.31514 　

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A 23-year-old man presented with headache, fever, and urinary retention. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests were positive, but SARS-CoV-2 polymerase chain reaction (PCR) results were negative. MRI showed long spinal cord lesions. Due to positive serum and cerebrospinal fluid myelin oligodendrocyte glycoprotein (MOG) antibodies, we made the diagnosis of MOG-associated disease. We concluded that the antigen tests were false positives because SARS-CoV-2 IgM and IgG were not elevated. Although the mechanism behind the false-positive results is unclear, physicians should consider the possibility of a false-positive result in the SARS-CoV-2 antigen test.
SARS-CoV-2ワクチン後免疫性神経疾患の臨床的特徴と予後

金子仁彦, 松本勇貴, 藤盛寿一, 生田目千尋, 高井良樹, 中島一郎, 三須建郎, 青木正志

NEUROINFECTION　27　(2)　214-214　2022/10
Publisher: 日本神経感染症学会
ISSN： 1348-2718

eISSN： 2435-2225
SARS-CoV-2ワクチン後免疫性神経疾患の臨床的特徴と予後

金子仁彦, 松本勇貴, 藤盛寿一, 生田目千尋, 高井良樹, 中島一郎, 三須建郎, 青木正志

NEUROINFECTION　27　(2)　214-214　2022/10
Publisher: 日本神経感染症学会
ISSN： 1348-2718

eISSN： 2435-2225
再発後早期にeculizumabを導入した抗アクアポリン4抗体陽性視神経脊髄炎の2例

金子仁彦, 浪岡靖弘, 大山綾音, 高井良樹, 檜森紀子, 中澤徹, 三須建郎, 青木正志

神経治療学　39　(4)　731-735　2022/07
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Relapse activity in the chronic phase of anti-myelin-oligodendrocyte glycoprotein antibody-associated disease. International-journal

Tetsuya Akaishi, Tatsuro Misu, Kazuo Fujihara, Toshiyuki Takahashi, Yoshiki Takai, Shuhei Nishiyama, Kimihiko Kaneko, Juichi Fujimori, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima

Journal of neurology　269　(6)　3136-3146　2022/06

DOI： 10.1007/s00415-021-10914-x 　

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OBJECTIVE: The patterns of relapse and relapse-prevention strategies for anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are not completely investigated. We compared the patterns of relapse in later stages of MOGAD with those of anti-aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this observational, comparative cohort study, 66 patients with MOGAD and 90 with AQP4-Ab-positive NMOSD were enrolled. We compared the patterns of relapse and annualized relapse rates (ARRs) in the first 10 years from disease onset, stratified by relapse-prevention treatments. RESULTS: Approximately 50% of the patients with MOGAD experienced relapses in the first 10 years. Among those not undergoing relapse-prevention treatments, ARRs in the first 5 years were slightly lower in MOGAD patients than in AQP4-Ab-positive NMOSD patients (MOGAD vs. AQP4-Ab NMOSD: 0.19 vs. 0.30; p = 0.0753). After 5 years, the ARR decreased in MOGAD patients (MOGAD vs. AQP4-Ab NMOSD: 0.05 vs. 0.34; p = 0.0001), with a 72% reduction from the first 5 years (p = 0.0090). Eight (61.5%) of the 13 MOGAD patients with more than 10-year follow-up from disease onset showed relapse 10 years after onset. Clustering in the timing and phenotype of attacks was observed in both disease patients. The effectiveness of long-term low-dose oral PSL for relapse prevention in patients with MOGAD has not been determined. CONCLUSIONS: The relapse risk in patients with MOGAD is generally lower than that in patients with AQP4-Ab-positive NMOSD, especially 5 years after onset. Meanwhile, relapses later than 10 years from onset are not rare in both diseases.
Follow-up of retinal thickness and optic MRI after optic neuritis in anti-MOG antibody-associated disease and anti-AQP4 antibody-positive NMOSD

Tetsuya Akaishi, Noriko Himori, Takayuki Takeshita, Tatsuro Misu, Toshiyuki Takahashi, Yoshiki Takai, Shuhei Nishiyama, Kimihiko Kaneko, Juichi Fujimori, Tadashi Ishii, Masashi Aoki, Kazuo Fujihara, Toru Nakazawa, Ichiro Nakashima

Journal of the Neurological Sciences　437　120269-120269　2022/06
Publisher: Elsevier BV
DOI： 10.1016/j.jns.2022.120269 　

ISSN： 0022-510X
多発性硬化症・視神経脊髄炎の治療トレンド最前線 Myelin oligodendrocyte glycoprotein抗体関連疾患の治療現状と課題

高井良樹, 三須建郎, 藤原一男, 青木正志

神経治療学　39　(3)　282-288　2022/05
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
SARS-CoV-2抗原検査にて偽陽性を呈したMOG抗体関連疾患の1例

山本尚輝, 池之内初, 高瀬啓至, 高橋利幸, 高井良樹, 遠藤薫, 青木正志

臨床神経学　62　(5)　407-407　2022/05
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Decreased subcortical T2 FLAIR signal with cortical T2 FLAIR hyperintense lesions in unilateral cerebral cortical encephalitis with myelin oligodendrocyte glycoprotein antibody

Juichi Fujimori, Ryo Ogawa, Takaki Murata, Yoshiki Takai, Tatsuro Misu, Ichiro Nakashima

Neuroimmunology Reports　100096-100096　2022/05
Publisher: Elsevier BV
DOI： 10.1016/j.nerep.2022.100096 　

ISSN： 2667-257X
MOG Antibody-Associated Disorders Following SARS-CoV-2 Vaccination: A Case Report and Literature Review

Yuki Matsumoto, Ayane Ohyama, Takafumi Kubota, Kensuke Ikeda, Kimihiko Kaneko, Yoshiki Takai, Hitoshi Warita, Toshiyuki Takahashi, Tatsuro Misu, Masashi Aoki

Frontiers in Neurology　13　2022/03/01
Publisher: Frontiers Media SA
DOI： 10.3389/fneur.2022.845755 　

eISSN： 1664-2295

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Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorder (MOGAD) is a newly identified autoimmune demyelinating disorder that is often associated with acute disseminated encephalomyelitis and usually occurs postinfection or postvaccination. Here we report a case of MOGAD after mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A previously healthy 68-year-old woman presented to our department with gradually worsening numbness on the right side of her face, which began 14 days after her second dose of an mRNA-1273 vaccination. The patient's brain MRI revealed a right cerebellar peduncle lesion with gadolinium enhancement, a typical finding of MOGAD. A neurological examination revealed paresthesia on her right V2 and V3 areas. Other neurological examinations were unremarkable. Laboratory workups were positive for serum MOG-IgG as assessed by live cell-based assays and the presence of oligoclonal bands in the cerebrospinal fluid (CSF). The patient's serum test results for cytoplasmic-antineutrophil cytoplasmic antibodies, perinuclear-cytoplasmic-antineutrophil cytoplasmic antibodies, GQ1b-antibodies, and aquaporin-4 antibodies (AQP4-IgG) were all negative. Tests for soluble interleukin (IL)-2 receptors in the serum, IL-6 in the CSF and skin pricks, and angiotensin converting enzyme tests were all unremarkable. The patient was diagnosed with MOGAD after receiving an mRNA SARS-CoV-2 vaccination. After two courses of intravenous methylprednisolone treatment, the patient's symptoms improved and her cerebellar peduncle lesion shrunk slightly without gadolinium enhancement. To date, there have only been two cases of monophasic MOGAD following SARS-CoV-2 vaccination, including both the ChAdOx1 nCOV-19 and mRNA-1273 vaccines, and the prognosis is generally similar to other typical MOGAD cases. Although the appearance of MOG antibodies is relatively rare in post-COVID-19–vaccine demyelinating diseases, MOGAD should be considered in patients with central nervous system (CNS) demyelinating diseases after receiving a SARS-CoV-2 vaccine.
RGMa signal in Macrophages Induces Neutrophil-related Astrocytopathy in NMO. International-journal

Shosuke Iwamoto, Takahide Itokazu, Atsushi Sasaki, Hirotoshi Kataoka, Shinji Tanaka, Takeshi Hirata, Keiko Miwa, Toshihiko Suenaga, Yoshiki Takai, Tatsuro Misu, Kazuo Fujihara, Toshihide Yamashita

Annals of neurology　2022/02/15

DOI： 10.1002/ana.26327 　

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OBJECTIVE: Repulsive guidance molecule-a (RGMa) is a glycosylphosphatidylinositol-linked glycoprotein which has multiple functions including axon growth inhibition and immune regulation. However, its role in the pathophysiology of neuromyelitis optica (NMO) is poorly understood. Perivascular astrocytopathy, which is induced by the leakage of aquaporin-4 (AQP4)-specific IgG into the central nervous system parenchyma, is a key feature of NMO pathology. We investigated the RGMa involvement in the pathology of NMO astrocytopathy, and tested a therapeutic potential of humanized anti-RGMa monoclonal antibody (RGMa-mAb). METHODS: Using a clinically relevant NMO rat model, we evaluated the therapeutic effect of a RGMa-mAb by behavioral testing, immunohistochemistry, and gene expression assay. We further performed in vitro experiments to address the RGMa-signaling in macrophages. RESULTS: In both NMO rats and an NMO-autopsied sample, RGMa was expressed by the spared neurons and astrocytes, whereas its receptor neogenin was expressed by infiltrating macrophages. AQP4-IgG-induced astrocytopathy and clinical exacerbation in NMO rats were ameliorated by RGMa-mAb treatment. RGMa-mAb treatment significantly suppressed neutrophil infiltration, and decreased the expression of neutrophil chemoattractants. Interestingly, neogenin-expressing macrophages accumulated in the lesion expressed CXCL2, a strong neutrophil chemoattractant, and further analysis revealed that RGMa directly regulated CXCL2 expression in macrophages. Finally, we found that our NMO rats developed neuropathic pain, and RGMa-mAb treatment effectively ameliorated the severity of neuropathic pain. INTERPRETATION: RGMa signaling in infiltrated macrophages is a critical driver of neutrophil-related astrocytopathy in NMO lesions, and RGMa-mAb may provide an efficient therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO. This article is protected by copyright. All rights reserved.
White blood cell count profiles in multiple sclerosis during attacks before the initiation of acute and chronic treatments. International-journal

Tetsuya Akaishi, Tatsuro Misu, Kazuo Fujihara, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Fumi Itabashi, Ikumi Kanno, Toshiyuki Takahashi, Hiroshi Kuroda, Juichi Fujimori, Yoshiki Takai, Shuhei Nishiyama, Kimihiko Kaneko, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima, Atsushi Hozawa

Scientific reports　11　(1)　22357-22357　2021/11/16

DOI： 10.1038/s41598-021-01942-8 　

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Multiple sclerosis (MS) is a major demyelinating disease of the central nervous system; however, its exact mechanism is unknown. This study aimed to elucidate the profile of white blood cells (WBCs) in the acute phase of an MS attack. Sixty-four patients with MS at the time of diagnosis and 2492 age- and sex-adjusted healthy controls (HCs) were enrolled. Data regarding the blood cell counts were compared between the groups. The total WBC (p < 0.0001), monocyte (p < 0.0001), basophil (p = 0.0027), and neutrophil (p < 0.0001) counts were higher in the MS group than in the HC group, whereas the lymphocyte and eosinophil counts did not differ. Adjustments for the smoking status and body mass index yielded the same results. The total and differential WBC counts of the patients with MS did not correlate with the counts of T2 hyperintense brain lesions or the levels of neurological disturbance. In summary, patients with MS showed elevated counts of total WBCs, monocytes, basophils, and neutrophils at the time of diagnosis. However, the clinical relevance of these biomarkers in the context of the development and progression of MS remains unclear.
リツキシマブが奏効した妊娠初期抗NMDA受容体脳炎の1例

保坂龍彦, 安藤大祐, 松本勇貴, 小野紘彦, 金子仁彦, 高井良樹, 菅野直人, 三須建郎, 青木正志

神経治療学　38　(6)　S277-S277　2021/10
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
視神経脊髄炎におけるアストロサイトパチーに基づいた新たな病期分類の確立と経時変化の解析

高井良樹, 三須建郎, 鈴木博義, 高橋利幸, 藤原一男, 青木正志

神経免疫学　26　(1)　80-80　2021/10
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体関連疾患における髄液中の抗MOG抗体測定の意義

松本勇貴, 金子仁彦, 三須建郎, 生田目知尋, 高井良樹, 黒田宙, 高橋利幸, 中島一郎, 藤原一男, 青木正志

神経免疫学　26　(1)　132-132　2021/10
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
視神経脊髄炎急性期における抗補体療法の有用性

金子仁彦, 浪岡靖弘, 大山綾音, 高井良樹, 三須建郎, 青木正志

神経免疫学　26　(1)　149-149　2021/10
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
Five-year visual outcomes after optic neuritis in anti-MOG antibody-associated disease. International-journal

Tetsuya Akaishi, Noriko Himori, Takayuki Takeshita, Tatsuro Misu, Toshiyuki Takahashi, Yoshiki Takai, Shuhei Nishiyama, Juichi Fujimori, Tadashi Ishii, Masashi Aoki, Kazuo Fujihara, Toru Nakazawa, Ichiro Nakashima

Multiple sclerosis and related disorders　56　103222-103222　2021/08/24

DOI： 10.1016/j.msard.2021.103222 　

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INTRODUCTION: Optic neuritis (ON) is a major phenotype of clinical attack related to demyelinating neurological diseases of the central nervous system, including multiple sclerosis (MS), anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). As the concept of MOGAD is relatively new, the long-term visual outcomes after ON in MOGAD remains unclear. METHODS: To elucidate the long-term visual prognosis after ON in MOGAD, patients with MOGAD whose visual acuity were regularly followed for more than 5 years from the onset of ON were enrolled. Best-corrected visual acuity (BCVA) at nadir in the acute phase and at 1 and 5 years from onset was evaluated. The data from patients with MOGAD were compared with those from patients with MS or anti-AQP4-positive NMOSD. RESULTS: Twenty-three patients (31 ON-involved eyes) with MOGAD, 20 patients (24 ON-involved eyes) with MS, and 22 patients (24 ON-involved eyes) with anti-AQP4-positive NMOSD were evaluated. All BCVA at nadir, 1 year, and 5 years from the onset of ON were much worse in anti-AQP4-positive NMOSD than in MS (p = 0.0024) and MOGAD (p = 0.0014) patients. In MOGAD and anti-AQP4-positive NMOSD, the serum disease-specific antibody titer was not associated with the subsequent visual prognosis. Visual acuity had almost fully recovered spontaneously or shortly after initiating acute treatment in 22 of the 23 patients with MOGAD-ON. The administration of high-dose intravenous steroid therapy further facilitated early recovery of visual acuity. Meanwhile, a small fraction of patients with extensive optic nerve lesions involving the chiasma irreversibly experienced severe visual impairment despite appropriate acute treatment. CONCLUSION: Although a small fraction of patients with MOGAD who presented with extensive optic nerve lesions experienced irreversible severe visual impairment, the long-term visual outcomes after 5 years from ON in patients with MOGAD were generally as good as that in patients with MS and much better than that in patients with anti-AQP4-positive NMOSD.
Asian and African/Caribbean AQP4-NMOSD patient outcomes according to self-identified race and place of residence. International-journal

Ricardo Soares-Dos-Reis, Jessica Li Tsz-Ching, Su-Hyun Kim, Anu Jacob, Daniel Whittam, Emeline Berthelot, Friedemann Paul, Ichiro Nakashima, Janis Siew Noi Tye, Jerôme De Seze, Jiraporn Jitprapaikulsan, Kevin Tan, Li Yang, Liene Elsone, Maria Isabel Leite, Maureen A Mealy, Michael Levy, Moli Fan, Nadja Siebert, Nasrin Asgari, Philippe Cabre, Sasitorn Siritho, Sean J Pittock, Stephen Cheng Wing-Ho, Thomas Senger, Tianrong Yeo, Yoshiki Takai, Lekha Pandit, Ho Jin Kim, Jacqueline Palace

Multiple sclerosis and related disorders　53　103080-103080　2021/08

DOI： 10.1016/j.msard.2021.103080 　

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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence. METHODS: This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three. RESULTS: Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups. CONCLUSION: This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors.
A rare case of sporadic inclusion body myositis and rheumatoid arthritis exhibiting ectopic lymphoid follicle-like structures: a case report and literature review. International-journal

Kazutoshi Konomatsu, Rumiko Izumi, Naoki Suzuki, Yoshiki Takai, Yuko Shirota, Ryoko Saito, Hiroshi Kuroda, Masashi Aoki

Neuromuscular disorders : NMD　31　(9)　870-876　2021/07/08

DOI： 10.1016/j.nmd.2021.07.002 　

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Sporadic inclusion body myositis (sIBM) is a degenerative, intractable, inflammatory myopathy with an immune pathomechanism. We report on a case of a 44-year-old Japanese man who began developing progressive muscle weakness at age 40. Rheumatoid arthritis symptoms manifested at 43 with strongly positive anti-cyclic citrullinated peptide antibodies. Along with typical sIBM pathology, a muscle biopsy revealed dramatic inflammation with prominent perivascular B-cell infiltration forming ectopic lymphoid follicle-like structures (ELFLSs). Exome sequencing identified no causative variants of hereditary myopathy or immune disorders. A combination of immunotherapy slowed the progression of the muscular symptoms. This unusual form of sIBM, including earlier age at onset, a partial response to immunotherapy, and a histopathology presenting B-cell infiltrate with ectopic lymphoid follicle-like structures, indicates a possible association of rheumatoid arthritis and heterogeneity with the autoimmune involvement of sIBM. We review the clinical and pathological features of patients with rheumatoid arthritis associated sIBM in the literature.
Difference in the Source of Anti-AQP4-IgG and Anti-MOG-IgG Antibodies in CSF in Patients With Neuromyelitis Optica Spectrum Disorder. International-journal

Tetsuya Akaishi, Toshiyuki Takahashi, Tatsuro Misu, Kimihiko Kaneko, Yoshiki Takai, Shuhei Nishiyama, Ryo Ogawa, Juichi Fujimori, Tadashi Ishii, Masashi Aoki, Kazuo Fujihara, Ichiro Nakashima

Neurology　97　(1)　e1-e12　2021/07/06

DOI： 10.1212/WNL.0000000000012175 　

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OBJECTIVE: To elucidate the differences in the source and in the level of intrathecal synthesis between anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). METHODS: Thirty-eight patients with MOG-IgG-associated disease and 36 with AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) were studied for the antibody titers in the sera and CSF simultaneously collected in the acute attacks. The quotients between CSF and serum levels of albumin, total immunoglobulin G, and each disease-specific antibody were calculated. Intrathecal production level in each disease-specific antibody was evaluated by calculating the antibody index from these quotients. RESULTS: Eleven of the 38 patients with MOG-IgG were positive for the antibody only in the CSF, while no patient with AQP4-IgG showed CSF-restricted AQP4-IgG. Blood-brain barrier compromise as shown by raised albumin quotients was seen in 75.0% of MOG-IgG-positive cases and 43.8% of AQP4-IgG-positive cases. Moreover, MOG-IgG quotients were >10 times higher than AQP4-IgG quotients (effect size r = 0.659, p < 0.0001). Elevated antibody index (>4.0) was confirmed in 12 of 21 with MOG-IgG, whereas it was seen only in 1 of 16 with AQP4-IgG (φ = 0.528, p < 0.0001). The CSF MOG-IgG titers (ρ = 0.519, p = 0.001) and antibody indexes for MOG-IgG (ρ = 0.472, p = 0.036) correlated with the CSF cell counts but not with clinical disability. CONCLUSIONS: Intrathecal production of MOG-IgG may occur more frequently than that of AQP4-IgG. This finding implies the different properties of B-cell trafficking and antibody production between MOG-IgG-associated disease and AQP4-IgG-positive NMOSD.
妊娠初期に急性精神症状で発症した自己免疫性脳炎の一例

保坂龍彦, 安藤大祐, 高橋幹弘, 松本勇貴, 小野紘彦, 高井良樹, 菅野直人, 三須建郎, 青木正志

臨床神経学　61　(7)　507-507　2021/07
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
一側上肢に限局する筋力低下を呈した抗GalNAc-GD1a IgG抗体陽性運動ニューロパチーの2例

大友瑞貴, 池田謙輔, 四條友望, 高井良樹, 菅野直人, 割田仁, 三須建郎, 青木正志

臨床神経学　61　(7)　509-509　2021/07
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Progression pattern of neurological disability with respect to clinical attacks in anti-MOG antibody-associated disorders International-journal

Tetsuya Akaishi, Tatsuro Misu, Toshiyuki Takahashi, Yoshiki Takai, Shuhei Nishiyama, Juichi Fujimori, Tadashi Ishii, Masashi Aoki, Kazuo Fujihara, Ichiro Nakashima

JOURNAL OF NEUROIMMUNOLOGY　351　577467-577467　2021/02

DOI： 10.1016/j.jneuroim.2020.577467 　

ISSN： 0165-5728

eISSN： 1872-8421
Early Treatment Initiation With Oral Prednisolone for Relapse Prevention Alleviates Depression and Fatigue in Aquaporin-4-Positive Neuromyelitis optica Spectrum Disorder International-journal

Tetsuya Akaishi, Toshiyuki Takahashi, Kazuo Fujihara, Tatsuro Misu, Juichi Fujimori, Yoshiki Takai, Shuhei Nishiyama, Michiaki Abe, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima

FRONTIERS IN NEUROLOGY　12　608149-608149　2021/02

DOI： 10.3389/fneur.2021.608149 　

ISSN： 1664-2295
Optimal management of neuromyelitis optica spectrum disorder with aquaporin-4 antibody by oral prednisolone maintenance therapy. International-journal

Yoshiki Takai, Hiroshi Kuroda, Tatsuro Misu, Tetsuya Akaishi, Ichiro Nakashima, Toshiyuki Takahashi, Shuhei Nishiyama, Kazuo Fujihara, Masashi Aoki

Multiple sclerosis and related disorders　49　102750-102750　2021/01/22

DOI： 10.1016/j.msard.2021.102750 　

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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing neuroinflammatory disease associated with aquaporin-4 antibody. Since disabilities in patients with NMOSD accumulate with attacks, relapse prevention is crucially important for improving long-term outcomes. Corticosteroids are inexpensive and promising drugs for relapse prevention in NMOSD, but few studies have analysed the efficacy of corticosteroids in NMOSD, especially regarding the appropriate dosing and tapering regimens. METHODS: A single-center, retrospective analysis of corticosteroid therapy in aquaporin-4 antibody-positive NMOSD patients fulfilling the 2015 international consensus diagnostic criteria was conducted. RESULTS: Medical records of a total of 89 Japanese patients with aquaporin-4 antibody-positive NMOSD seen at Department of Neurology, Tohoku University Hospital (2000~2016) were reviewed. At the last follow-up, 66% of the patients were treated with prednisolone (PSL) monotherapy, and the percentage of those receiving PSL monotherapy or a combination of PSL and other immunosuppressants increased from 17.5% in 2000 to 94.1% in 2016. On the other hand, annualised relapse rate (ARR) decreased from 0.78 (13 attacks in 200 person-months) in 2000 to 0.07 (5 attacks in 819 person-months) in 2016. Under PSL treatment, the mean ARR significantly decreased, and disabilities stabilized (PSL treatment vs no-medication; ARR: 0.21 vs 0.98, P < 0.01, Expanded Disability Status Scale score change: +0.02 vs +0.89, P < 0.01, observation periods: 60.1 vs 68.2 months, P=0.26). Using Kaplan-Meier curves, the 10-year relapse-free rate was 46.5% with PSL monotherapy and 7.1% with no medication (hazard ratio: 0.069, 95% confidence interval [CI] 0.024-0.199, P < 0.01). Rapid tapering of PSL (10 mg or less in one year and/or 5 mg or less in two years after clinical attacks) was associated with frequent relapses compared to gradual tapering (more than 10 mg in one year and more than 5 mg in two years after clinical attacks) (rapid vs gradual, 36.7% vs 17.7%, odds ratio 2.69, 95% CI 1.12-6.44, P = 0.02). However, even with PSL of 5 mg/day or less, the relapse rate was low after two years of acute treatment (before vs after, 53.8% vs 13.6%, odds ratio 0.12, 95% CI 0.03-0.50, P < 0.01). Nine patients needed additional immunosuppressants due to insufficient relapse prevention by PSL monotherapy. PSL monotherapy was generally well tolerated, but seven patients had severe adverse events, mainly bone fractures (5 with bone fracture, 1 with femoral capital necrosis and 1 with cerebral infarction). CONCLUSION: Our study suggests that PSL monotherapy is effective to prevent relapses in about half of patients with aquaporin-4 antibody-positive NMOSD if the doses are gradually reduced. Although it is important to have a treatment strategy tailored to each patient, this study provides evidence that PSL monotherapy can be an option for relapse prevention in some patients with NMOSD.
Impact of comorbid Sjogren syndrome in anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders International-journal

Tetsuya Akaishi, Toshiyuki Takahashi, Kazuo Fujihara, Tatsuro Misu, Juichi Fujimori, Yoshiki Takai, Shuhei Nishiyama, Michiaki Abe, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima

JOURNAL OF NEUROLOGY　2021/01

DOI： 10.1007/s00415-020-10377-6 　

ISSN： 0340-5354

eISSN： 1432-1459
CH50 as a putative biomarker of eculizumab treatment in neuromyelitis optica spectrum disorder International-journal

Chihiro Namatame, Tatsuro Misu, Yoshiki Takai, Shuhei Nishiyama, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

HELIYON　7　(1)　e05899　2021/01

DOI： 10.1016/j.heliyon.2021.e05899 　

ISSN： 2405-8440
Distinctive lesions of brain MRI between MOG-antibody-associated and AQP4-antibody-associated diseases. International-journal

Yuki Matsumoto, Tatsuro Misu, Shunji Mugikura, Yoshiki Takai, Shuhei Nishiyama, Hiroshi Kuroda, Toshiyuki Takahashi, Juichi Fujimori, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

Journal of neurology, neurosurgery, and psychiatry　2020/12/30

DOI： 10.1136/jnnp-2020-324818 　
Seasonal variation of onset in patients with anti-aquaporin-4 antibodies and anti-myelin oligodendrocyte glycoprotein antibody International-journal

Tetsuya Akaishi, Juichi Fujimori, Toshiyuki Takahashi, Tatsuro Misu, Yoshiki Takai, Shuhei Nishiyama, Kimihiko Kaneko, Ryo Ogawa, Michiaki Abe, Tadashi Ishii, Masashi Aoki, Kazuo Fujihara, Ichiro Nakashima

JOURNAL OF NEUROIMMUNOLOGY　349　577431-577431　2020/12

DOI： 10.1016/j.jneuroim.2020.577431 　

ISSN： 0165-5728

eISSN： 1872-8421
臨床的に多発性硬化症と診断される抗MOG抗体陽性患者の検討

生田目知尋, 三須建郎, 高橋利幸, 小川諒, 金子仁彦, 高井良樹, 西山修平, 中島一郎, 藤原一男, 青木正志

臨床神経学　60　(Suppl.)　S436-S436　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
著明な鉄欠乏性貧血を誘因とした中枢神経内多発血管症(Susac症候群)の一例

保坂龍彦, 原田龍平, 高井良樹, 菅野直人, 割田仁, 青木正志

臨床神経学　60　(11)　799-799　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
脳脊髄液糖減少をともなう無菌性髄膜炎で再発した抗MOG抗体関連疾患の一例

大友瑞貴, 安藤大祐, 千葉菜々絵, 高井良樹, 三須建郎, 菅野直人, 割田仁, 青木正志

臨床神経学　60　(11)　800-800　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
臨床的に多発性硬化症と診断される抗MOG抗体陽性患者の検討

生田目知尋, 三須建郎, 高橋利幸, 小川諒, 金子仁彦, 高井良樹, 西山修平, 中島一郎, 藤原一男, 青木正志

臨床神経学　60　(Suppl.)　S436-S436　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
著明な鉄欠乏性貧血を誘因とした中枢神経内多発血管症(Susac症候群)の一例

保坂龍彦, 原田龍平, 高井良樹, 菅野直人, 割田仁, 青木正志

臨床神経学　60　(11)　799-799　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
脳脊髄液糖減少をともなう無菌性髄膜炎で再発した抗MOG抗体関連疾患の一例

大友瑞貴, 安藤大祐, 千葉菜々絵, 高井良樹, 三須建郎, 菅野直人, 割田仁, 青木正志

臨床神経学　60　(11)　800-800　2020/11
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
中枢病変を伴わない末梢神経障害における抗MOG抗体連続37例での検討

金子仁彦, 佐藤ダグラス, 高橋利幸, 高井良樹, 西山修平, 三須建郎, 中島一郎, 藤原一男, 青木正志

神経免疫学　25　(1)　151-151　2020/10
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
臨床的に多発性硬化症と診断される抗MOG抗体陽性患者の検討

生田目知尋, 三須建郎, 高橋利幸, 小川諒, 金子仁彦, 高井良樹, 西山修平, 中島一郎, 藤原一男, 青木正志

神経免疫学　25　(1)　152-152　2020/10
Publisher: (一社)日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体及び抗AQP4抗体陽性疾患の頭部MRI画像における病変分布の比較検討

松本勇貴, 三須建郎, 麦倉俊司, 高井良樹, 西山修平, 黒田宙, 高橋利幸, 藤盛寿一, 中島一郎, 藤原一男, 青木正志

神経免疫学　25　(1)　104-104　2020/10
Publisher: 日本神経免疫学会
ISSN： 0918-936X
Impact of intrathecal IgG synthesis on neurological disability in patients with multiple sclerosis International-journal Peer-reviewed

Tetsuya Akaishi, Toshiyuki Takahashi, Kazuo Fujihara, Tatsuro Misu, Shuhei Nishiyama, Yoshiki Takai, Juichi Fujimori, Michiaki Abe, Tadashi Ishii, Masashi Aoki, Ichiro Nakashima

MULTIPLE SCLEROSIS AND RELATED DISORDERS　45　102382-102382　2020/10

DOI： 10.1016/j.msard.2020.102382 　

ISSN： 2211-0348

eISSN： 2211-0356
Endothelial damage in patients with neuromyelitis optica spectrum disorder with aquaporin-4 IgG

Hiroshi Kuroda, Yoshiki Takai, Shuhei Nishiyama, Toshiyuki Takahashi, Tatsuro Misu, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　26　(9)　NP77-NP78　2020/08

ISSN： 1352-4585

eISSN： 1477-0970
Elevated cerebrospinal fluid-CRMP5 levels in acute phase of NMOSD with AQP4-IgG and the prognostic implication

Shuhei Nishiyama, Tatsuro Misu, Yoshiki Takai, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　26　(9)　NP77-NP77　2020/08

ISSN： 1352-4585

eISSN： 1477-0970
Perivenous demyelination: Association with anti-myelin oligodendrocyte glycoprotein antibody

Tatsuro Misu, Yoshiki Takai, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

Clinical and Experimental Neuroimmunology　11　(S1)　22-27　2020/03/01

DOI： 10.1111/cen3.12569 　

eISSN： 1759-1961
T-cell Lymphoma Presenting Neutrophilic Inflammation in the Cerebrospinal Fluid Peer-reviewed

Takaaki Nakamura, Yoshiki Takai, Kimihiko Kaneko, Hiroshi Kuroda, Tatsuro Misu, Kiyotaka Asanuma, Ryoko Saito, Masashi Aoki

INTERNAL MEDICINE　59　(4)　573-576　2020

DOI： 10.2169/internalmedicine.3093-19 　

ISSN： 0918-2918

eISSN： 1349-7235
治療抵抗性の重症抗MOG抗体関連疾患に対するリツキシマブの使用経験

松本勇貴, 三須建郎, 高井良樹, 西山修平, 小野紘彦, 黒田宙, 割田仁, 青木正志, 黒澤和大, 清水洋, 藤原一男

神経治療学　36　(6)　S288-S288　2019/10
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
FDG-PET detects extensive calcinosis cutis in anti-NXP2 antibody-positive dermatomyositis International-journal Peer-reviewed

Naoko Nakamura, Rumiko Izumi, Yosuke Hoshi, Yoshiki Takai, Risako Ono, Naoki Suzuki, Taichi Nagai, Yusho Ishii, Tomonori Ishii, Hideo Harigae, Shuko Okada, Setsuya Aiba, Naoko Okiyama, Manabu Fujimoto, Hiroshi Kuroda, Maki Tateyama, Masashi Aoki

RHEUMATOLOGY　58　(10)　1888-1888　2019/10

DOI： 10.1093/rheumatology/kez083 　

ISSN： 1462-0324

eISSN： 1462-0332
Long-term outcome of a group of Japanese children with myelin-oligodendrocyte glycoprotein encephalomyelitis without preventive immunosuppressive therapy International-journal Peer-reviewed

Naomi Hino-Fukuyo, Kazuhiro Haginoya, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara, Yoshiki Takai, Manami Akasaka, Shigeo Kure

BRAIN & DEVELOPMENT　41　(9)　790-795　2019/10

DOI： 10.1016/j.braindev.2019.06.004 　

ISSN： 0387-7604

eISSN： 1872-7131
自己免疫性脳炎抗MOG抗体陽性患者におけるT細胞反応性に関する検討

小野紘彦, 三須建郎, 高井良樹, 西山修平, 黒田宙, 高橋利幸, 中島一郎, 藤原一男, 青木正志

神経免疫学　24　(1)　96-96　2019/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
MS/NMO 2 視神経脊髄炎中枢組織障害に対するIL-6の影響に関する病理学的検討

高井良樹, 三須建郎, 松本勇貴, 生田目知尋, 小野紘彦, 西山修平, 黒田宙, 藤原一男, 青木正志

神経免疫学　24　(1)　118-118　2019/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体関連疾患急性期治療後の経時的障害度と予後の検討

生田目知尋, 三須建郎, 西山修平, 高井良樹, 小野紘彦, 松本勇貴, 高橋利幸, 中島一郎, 藤原一男, 青木正志

神経免疫学　24　(1)　153-153　2019/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
Two Japanese cases of anti-MOG antibody-associated encephalitis that mimicked neuro-Behcet's disease International-journal Peer-reviewed

Juichi Fujimori, Toshiyuki Takahashi, Yuki Matsumoto, Kazuo Fujihara, Yoshiki Takai, Tatsuro Misu, Ichiro Nakashima

JOURNAL OF NEUROIMMUNOLOGY　334　577002-577002　2019/09

DOI： 10.1016/j.jneuroim.2019.577002 　

ISSN： 0165-5728

eISSN： 1872-8421
再発予防投与を行わなかった抗MOG抗体陽性小児患者における長期予後

福與なおみ, 萩野谷和裕, 高橋利幸, 中島一郎, 藤原一男, 高井良樹, 赤坂真奈美, 呉繁夫

脳と発達　51　(Suppl.)　S270-S270　2019/05
Publisher: (一社)日本小児神経学会
ISSN： 0029-0831

eISSN： 1884-7668
Outcome prediction models in AQP4-IgG positive neuromyelitis optica spectrum disorders International-journal Peer-reviewed

Jacqueline Palace, Dan-Yu Lin, Donglin Zeng, Masoud Majed, Liene Elsone, Shand Hamid, Silvia Messina, Tatsuro Misu, Jessica Sagen, Daniel Whittam, Yoshiki Takai, Maria Isabel Leite, Brian Weinshenker, Philippe Cabre, Anu Jacob, Ichiro Nakashima, Kazuo Fujihara, Sean J. Pittock

BRAIN　142　(5)　1310-1323　2019/05

DOI： 10.1093/brain/awz054 　

ISSN： 0006-8950

eISSN： 1460-2156
Interstitial pneumonia and other adverse events in riluzole-administered amyotrophic lateral sclerosis patients: a retrospective observational study International-journal Peer-reviewed

Aya Inoue-Shibui, Masaaki Kato, Naoki Suzuki, Junpei Kobayashi, Yoshiki Takai, Rumiko Izumi, Yuuko Kawauchi, Hiroshi Kuroda, Hitoshi Warita, Masashi Aoki

BMC NEUROLOGY　19　(1)　72-72　2019/04

DOI： 10.1186/s12883-019-1299-1 　

ISSN： 1471-2377
The relevance of cerebrospinal fluid polymorphonuclear leukocytes in diagnosis of inflammatory CNS diseases

Hiroshi Kuroda, Kimihiko Kaneko, Ryo Ogawa, Yoshiki Takai, Shuhei Nishiyama, Toshiyuki Takahashi, Tatsuro Misu, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　25　(3)　479-479　2019/03

ISSN： 1352-4585

eISSN： 1477-0970
Circulating AQP4-specific auto-antibodies alone can induce neuromyelitis optica spectrum disorder in the rat International-journal Peer-reviewed

Sophie Hillebrand, Kathrin Schanda, Magdalini Nigritinou, Irina Tsymala, Denise Boehm, Patrick Peschl, Yoshiki Takai, Kazuo Fujihara, Ichiro Nakashima, Tatsuro Misu, Markus Reindl, Hans Lassmann, Monika Bradl

ACTA NEUROPATHOLOGICA　137　(3)　467-485　2019/03

DOI： 10.1007/s00401-018-1950-8 　

ISSN： 0001-6322

eISSN： 1432-0533
The pathological features of MOG antibody-positive cerebral cortical encephalitis as a new spectrum associated with MOG antibodies

Toshimasa Ikeda, Kentaro Yamada, Tatsuro Misu, Ryo Ogawa, Yoshiki Takai, Maya Mimuro, Yasushi Iwasaki, Kaoru Kamimoto, Noriyuki Matsukawa, Mari Yoshida

BRAIN PATHOLOGY　29　15-15　2019/02

ISSN： 1015-6305

eISSN： 1750-3639
Perivenous inflammatory demyelination is the prominent pathology in myelin oligodendrocyte glycoprotein antibody-associated disease

Yoshiki Takai, Misu Tatsuro, Kaneko Kimihiko, Norio Chihara, Kouidhi Narikawa, Satoko Tsuchida, Hiroya Nishida, Takahashi Toshiyuki, Masashi Aoki, Fujihara Kazuo

BRAIN PATHOLOGY　29　13-13　2019/02

ISSN： 1015-6305

eISSN： 1750-3639
抗MOG抗体関連疾患に対する血漿交換療法add-onの有効性に関する検討

生田目知尋, 西山修平, 三須建郎, 高井良樹, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経治療学　35　(6)　S220-S220　2018/11
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
再発寛解型多発性硬化症に対してNatalizumabを使用した11例の検討

西山修平, 三須建郎, 高井良樹, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経治療学　35　(6)　S221-S221　2018/11
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
異なる経過をたどり抗MOG抗体陽性であった中枢神経単純ヘルペス感染症の2例

金子仁彦, 佐藤ダグラス, 高橋利幸, 小川諒, 高井良樹, 西山修平, 三須建郎, 黒田宙, 佐藤亮介, 小林修, 田中覚, 田島孝士, 中島一郎, 藤原一男, 青木正志

NEUROINFECTION　23　(2)　221-221　2018/10
Publisher: 日本神経感染症学会
ISSN： 1348-2718

eISSN： 2435-2225
Area postrema syndrome Frequency, criteria, and severity in AQP4-IgG-positive NMOSD International-journal Peer-reviewed

Eslam Shosha, Divyanshu Dubey, Jacqueline Palace, Ichiro Nakashima, Anu Jacob, Kazuo Fujihara, Toshiyuki Takahashi, Daniel Whittam, Maria Isabel Leite, Tatsuro Misu, Takai Yoshiki, Silvia Messina, Liene Elsone, Masoud Majed, Eoin Flanagan, Avi Gadoth, Carey Huebert, Jessica Sagen, Benjamin M. Greenberg, Michael Levy, Aditya Banerjee, Brian Weinshenker, Sean J. Pittock

NEUROLOGY　91　(17)　E1642-E1651　2018/10

DOI： 10.1212/WNL.0000000000006392 　

ISSN： 0028-3878

eISSN： 1526-632X
急性脳炎・脳症中枢神経系の単純ヘルペス感染の関与が疑われた抗MOG抗体陽性神経疾患の2例

金子仁彦, 佐藤ダグラス, 高橋利幸, 小川諒, 高井良樹, 西山修平, 三須建郎, 黒田宙, 佐藤亮介, 小林修

神経免疫学　23　(1)　95-95　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
MS/NMO 抗MOG抗体関連性脱髄病巣の病理学的特徴

高井良樹, 三須建郎, 金子仁彦, 高橋利幸, 成川孝一, 千原典夫, 西田裕哉, 土田聡子, 青木正志, 藤原一男

神経免疫学　23　(1)　108-108　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
再発寛解型多発性硬化症に対するNatalizumabの使用経験11例での検討

西山修平, 三須建郎, 高井良樹, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経免疫学　23　(1)　114-114　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体陽性皮質脳炎の臨床病理像

池田知雅, 山田健太郎, 小川諒, 高井良樹, 金子仁彦, 三須建郎, 紙本薫, 松川則之, 吉田眞理

神経免疫学　23　(1)　116-116　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
炎症性中枢神経疾患における髄液多形核白血球増多例の検討

黒田宙, 金子公彦, 小川諒, 高井良樹, 西山修平, 三須建郎, 中島一郎, 藤原一男, 青木正志

神経免疫学　23　(1)　126-126　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体関連疾患に対する血漿交換療法add-onの有効性に関する検討

生田目知尋, 西山修平, 三須建郎, 高井良樹, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経免疫学　23　(1)　131-131　2018/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
CSF cytokine profile in MOG-IgG plus neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications Peer-reviewed

Kimihiko Kaneko, Douglas Kazutoshi Sato, Ichiro Nakashima, Ryo Ogawa, Tetsuya Akaishi, Yoshiki Takai, Shuhei Nishiyama, Toshiyuki Takahashi, Tatsuro Misu, Hiroshi Kuroda, Satoru Tanaka, Kyoichi Nomura, Yuji Hashimoto, Dagoberto Callegaro, Lawrence Steinman, Kazuo Fujihara, Masashi Aoki

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY　89　(9)　927-936　2018/09

DOI： 10.1136/jnnp-2018-317969 　

ISSN： 0022-3050

eISSN： 1468-330X
The pathological features of MOG antibody-positive cerebral cortical encephalitis as a new spectrum associated with MOG antibodies: A case report Peer-reviewed

Toshimasa Ikeda, Kentaro Yamada, Ryo Ogawa, Yoshiki Takai, Kimihiko Kaneko, Tatsuro Misu, Kaoru Kamimoto, Noriyuki Matsukawa, Mari Yoshida

JOURNAL OF THE NEUROLOGICAL SCIENCES　392　113-115　2018/09

DOI： 10.1016/j.jns.2018.06.028 　

ISSN： 0022-510X

eISSN： 1878-5883
Discrimination of Spinal Cord Sarcoidosis from Neuromyelitis Optica Spectrum Disorer or Spondylotic Myelopathy

Hiroshi Kuroda, Toshiyuki Takahashi, Douglas Kazutoshi Sato, Ryo Ogawa, Kimihiko Kaneko, Yoshiki Takai, Shuhei Nishiyama, Tatsuro Misu, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　24　(3)　380-380　2018/03

ISSN： 1352-4585

eISSN： 1477-0970
Cerebrospilnal Fluid-Actin Related Protein 2/3 Complex Subunit 4 as an Astrocytic Foot Process Damage Marker of Aquaporin-4-Igg Positive Neuromyelitis Optica Spectrum Disorders

Shuhei Nishiyama, Tatsuro Misu, Ichiro Nakashima, Douglas Kazutoshi Sato, Kimihiko Kaneko, Ryo Ogawa, Hirohiko Ono, Kazuhiro Kurosawa, Yoshiki Takai, Toshiyuki Takahashi, Hiroshi Kuroda, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　24　(3)　380-380　2018/03

ISSN： 1352-4585

eISSN： 1477-0970
Fingolimod-Associated PML with Mild Immune Reconstitution Inflammatory Syndrome in Multiple Sclerosis

Shuhei Nishiyama, Tatsuro Misu, Yukiko Shishido-Hara, Kazuo Nakamichi, Masayuki Saijo, Yoshiki Takai, Kentarou Takei, Naoki Yamamoto, Hiroshi Kuroda, Ryuta Saito, Mika Watanabe, Teiji Tominaga, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　24　(3)　381-382　2018/03

ISSN： 1352-4585

eISSN： 1477-0970
Myelin oligodendrocyte glycoprotein immunoglobulin G-associated disease: An overview

Kazuo Fujihara, Kazuo Fujihara, Kazuo Fujihara, Douglas K. Sato, Douglas K. Sato, Ichiro Nakashima, Ichiro Nakashima, Toshiyuki Takahashi, Toshiyuki Takahashi, Kimihiko Kaneko, Ryo Ogawa, Tetsuya Akaishi, Yuki Matsumoto, Yoshiki Takai, Shuhei Nishiyama, Hiroshi Kuroda, Tatsuro Misu, Tatsuro Misu, Masashi Aoki

Clinical and Experimental Neuroimmunology　9　48-55　2018/03/01

DOI： 10.1111/cen3.12434 　

eISSN： 1759-1961
Fingolimod-associated PML with mild IRIS in MS A clinicopathologic study International-journal Peer-reviewed

Shuhei Nishiyama, Tatsuro Misu, Yukiko Shishido-Hara, Kazuo Nakamichi, Masayuki Saijo, Yoshiki Takai, Kentarou Takei, Naoki Yamamoto, Hiroshi Kuroda, Ryuta Saito, Mika Watanabe, Teiji Tominaga, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION　5　(1)　e415　2018/01

DOI： 10.1212/NXI.0000000000000415 　

ISSN： 2332-7812
視神経脊髄炎関連疾患に対する経口ステロイド維持療法の最適化

高井良樹, 中島一郎, 三須建郎, 黒田宙, 西山修平, 高橋利幸, 藤原一男, 青木正志

神経治療学　34　(6)　S221-S221　2017/11
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Bilateral frontal cortex encephalitis and paraparesis in a patient with anti-MOG antibodies Peer-reviewed

Juichi Fujimori, Yoshiki Takai, Ichiro Nakashima, Douglas Kazutoshi Sato, Toshiyuki Takahashi, Kimihiko Kaneko, Shuhei Nishiyama, Mika Watanabe, Hiroaki Tanji, Michiko Kobayashi, Tatsuro Misu, Masashi Aoki, Kazuo Fujihara

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY　88　(6)　534-536　2017/06

DOI： 10.1136/jnnp-2016-315094 　

ISSN： 0022-3050

eISSN： 1468-330X
Impact of the Great East Japan Earthquake in 2011 on MS and NMOSD: a study in Sendai, Japan Peer-reviewed

Yoko Kanamori, Ichiro Nakashima, Yoshiki Takai, Tatsuro Misu, Hiroshi Kuroda, Shuhei Nishiyama, Toshiyuki Takahashi, Shigeru Sato, Juichi Fujimori, Jun Higuchi, Yasuto Itoyama, Masashi Aoki, Kazuo Fujihara

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY　88　(4)　362-+　2017/04

DOI： 10.1136/jnnp-2016-313890 　

ISSN： 0022-3050

eISSN： 1468-330X
MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy Peer-reviewed

Ryo Ogawa, Ichiro Nakashima, Toshiyuki Takahashi, Kimihiko Kaneko, Tetsuya Akaishi, Yoshiki Takai, Douglas Kazutoshi Sato, Shuhei Nishiyama, Tatsuro Misu, Hiroshi Kuroda, Masashi Aoki, Kazuo Fujihara

NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION　4　(2)　e322　2017/03

DOI： 10.1212/NXI.0000000000000322 　

ISSN： 2332-7812
Adult MOG-Igg-Positive, Benign, Unilateral, Cerebral Cortical Encephalitis with Epileptic Seizure Peer-reviewed

Ryo Ogawa, Ichiro Nakashima, Toshiyuki Takahashi, Hirohiko Ono, Kimihiko Kaneko, Tetsuya Akaishi, Kazuhiro Kurosawa, Yoshiki Takai, Douglas Kazutoshi Sato, Shuhei Nishiyama, Tatsuro Misu, Hiroshi Kuroda, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　23　(2)　352-352　2017/02

ISSN： 1352-4585

eISSN： 1477-0970
Hypoxia-like tissue injury and glial response contribute to Balo concentric lesion development Peer-reviewed

Yoshiki Takai, Tatsuro Misu, Shuhei Nishiyama, Hirohiko Ono, Hiroshi Kuroda, Ichiro Nakashima, Ryuta Saito, Masayuki Kanamori, Yukihiko Sonoda, Toshihiro Kumabe, Shunji Mugikura, Mika Watanabe, Masashi Aoki, Kazuo Fujihara

NEUROLOGY　87　(19)　2000-2005　2016/11

DOI： 10.1212/WNL.0000000000003308 　

ISSN： 0028-3878

eISSN： 1526-632X
The binding property of a monoclonal antibody against the extracellular domains of aquaporin-4 directs aquaporin-4 toward endocytosis Peer-reviewed

Ping Huang, Yoshiki Takai, Osamu Kusano-Arai, Julia Ramadhanti, Hiroko Iwanari, Takayuki Miyauchi, Toshiko Sakihama, Jing-Yan Han, Masashi Aoki, Takao Hamakubo, Kazuo Fujihara, Masato Yasui, Yoichiro Abe

Biochemistry and Biophysics Reports　7　77-83　2016/09/01
Publisher: Elsevier B.V.
DOI： 10.1016/j.bbrep.2016.05.017 　

ISSN： 2405-5808
Astrocyte Injury and Secondary Demyelination Induced by Intracerebral Injection of AQP4-IgG and Complement in Mouse Brain Peer-reviewed

Yoshiki Takai, Yoichiro Abe, Tasturo Misu, Kazuhiro Kurosawa, Toshiyuki Takahashi, Hiroshi Kuroda, Ichiro Nakashima, Shuhei Nishiyama, Masato Yasui, Kazuo Fujihara, Masashi Aoki

MULTIPLE SCLEROSIS JOURNAL　22　(3)　403-404　2016/03

ISSN： 1352-4585

eISSN： 1477-0970
High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with the neuromyelitis optica autoantibody, NMO-IgG Peer-reviewed

Kaori Miyazaki-Komine, Yoshiki Takai, Ping Huang, Osamu Kusano-Arai, Hiroko Iwanari, Tatsuro Misu, Katsushi Koda, Katsuyuki Mitomo, Toshiko Sakihama, Yoshiaki Toyama, Kazuo Fujihara, Takao Hamakubo, Masato Yasui, Yoichiro Abe

BRITISH JOURNAL OF PHARMACOLOGY　173　(1)　103-114　2016/01

DOI： 10.1111/bph.13340 　

ISSN： 0007-1188

eISSN： 1476-5381
Pregnancy outcomes in aquaporin-4-positive neuromyelitis optica spectrum disorder Peer-reviewed

Matthew M. Nour, Ichiro Nakashima, Ester Coutinho, Mark Woodhall, Filipa Sousa, Jon Revis, Yoshiki Takai, Jithin George, Joanna Kitley, Maria Ernestina Santos, Joseph M. Nour, Fan Cheng, Hiroshi Kuroda, Tatsuro Misu, Ana Martins-da-Silva, Gabriele C. DeLuca, Angela Vincent, Jacqueline Palace, Patrick Waters, Kazuo Fujihara, Maria Isabel Leite

NEUROLOGY　86　(1)　79-87　2016/01

DOI： 10.1212/WNL.0000000000002208 　

ISSN： 0028-3878

eISSN： 1526-632X
Severely exacerbated neuromyelitis optica rat model with extensive astrocytopathy by high affinity anti-aquaporin-4 monoclonal antibody Peer-reviewed

Kazuhiro Kurosawa, Tatsuro Misu, Yoshiki Takai, Douglas Kazutoshi Sato, Toshiyuki Takahashi, Yoichiro Abe, Hiroko Iwanari, Ryo Ogawa, Ichiro Nakashima, Kazuo Fujihara, Takao Hamakubo, Masato Yasui, Masashi Aoki

ACTA NEUROPATHOLOGICA COMMUNICATIONS　3　82　2015/12

DOI： 10.1186/s40478-015-0259-2 　

ISSN： 2051-5960
High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with NMO-IgG

Kaori Miyazaki-Komine, Yoichiro Abe, Ping Huang, Yoshiki Takai, Osamu Arai, Hiroko Iwanari, Tatsuro Misu, Toshiko Sakihama, Yoshiaki Toyama, Kazuo Fujihara, Takao Hamakubo, Masato Yasui

JOURNAL OF PHARMACOLOGICAL SCIENCES　128　(3)　S247-S247　2015/07

ISSN： 1347-8613

eISSN： 1347-8648
Expression and localization of aquaporin-4 in sensory ganglia Peer-reviewed

Jungo Kato, Yoshiki Takai, Mariko Kato Hayashi, Yasuhiro Kato, Manami Tanaka, Yoshiro Sohma, Yoichiro Abe, Masato Yasui

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　451　(4)　562-567　2014/09

DOI： 10.1016/j.bbrc.2014.08.026 　

ISSN： 0006-291X

eISSN： 1090-2104
Brainstem manifestations in neuromyelitis optica: a multicenter study of 258 patients Peer-reviewed

L. Kremer, M. Mealy, A. Jacob, I. Nakashima, P. Cabre, S. Bigi, F. Paul, S. Jarius, O. Aktas, L. Elsone, K. Mutch, M. Levy, Y. Takai, N. Collongues, B. Banwell, K. Fujihara, J. de Seze

MULTIPLE SCLEROSIS JOURNAL　20　(7)　843-847　2014/06

DOI： 10.1177/1352458513507822 　

ISSN： 1352-4585

eISSN： 1477-0970
脳幹部初発のAIDS合併PMLの1例

澁井彩, 高橋志緒, 田代亮介, 笠原祥子, 岡直美, 小川諒, 小野洋也, 千葉哲矢, 渡辺源也, 赤石哲也, 高井良樹, 突田健一, 成川孝一, 鈴木靖士, 栗原紀子, 伊藤俊広

臨床神経学　54　(3)　241-241　2014/03
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
典型的ミトコンドリア遺伝子異常が同定されなかったMELASの1例

加賀谷由里子, 赤石哲也, 吉野祐貴, 小田桐裕香, 押切みすず, 高橋志緒, 高井良樹, 千葉哲矢, 渡辺源也, 突田健一, 成川孝一, 鈴木靖士

臨床神経学　54　(3)　244-244　2014/03
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
視神経脊髄炎の1剖検例

桂永行, 小泉文人, 紺野加奈子, 山形宗久, 笹生俊一, 深浦彦彰, 三須建郎, 高井良樹

神経治療学　30　(5)　693-693　2013/09
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica Peer-reviewed

Tatsuro Misu, Romana Hoeftberger, Kazuo Fujihara, Isabella Wimmer, Yoshiki Takai, Shuhei Nishiyama, Ichiro Nakashima, Hidehiko Konno, Monika Bradl, Ferenc Garzuly, Yasuto Itoyama, Masashi Aoki, Hans Lassmann

ACTA NEUROPATHOLOGICA　125　(6)　815-827　2013/06

DOI： 10.1007/s00401-013-1116-7 　

ISSN： 0001-6322

eISSN： 1432-0533
Aquaporin-4 antibody-positive cases beyond current diagnostic criteria for NMO spectrum disorders Peer-reviewed

Douglas Kazutoshi Sato, Ichiro Nakashima, Toshiyuki Takahashi, Tatsuro Misu, Patrick Waters, Hiroshi Kuroda, Shuhei Nishiyama, Chihiro Suzuki, Yoshiki Takai, Kazuo Fujihara, Yasuto Itoyama, Masashi Aoki

NEUROLOGY　80　(24)　2210-2216　2013/06

DOI： 10.1212/WNL.0b013e318296ea08 　

ISSN： 0028-3878

eISSN： 1526-632X
NMO spectrum disorders and anti AQP4 antibody Peer-reviewed

Yoshiki Takai, Tatsuro Misu, Toshiyuki Takahashi, Ichiro Nakashima, Kazuo Fujihara

Brain and Nerve　65　(4)　333-343　2013/04

ISSN： 1881-6096
asterixisと失調を伴ったRamsay-Hunt症候群の1例

千葉哲矢, 高井良樹, 突田健一, 渡辺源也, 成川孝一, 鈴木靖士

臨床神経学　53　(3)　265-265　2013/03
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
The Importance of Aquaporin-4 Antibody Assays in Patients beyond the Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders Peer-reviewed

Douglas Sato, Ichiro Nakashima, Toshiyuki Takahashi, Tatsuro Misu, Patrick Waters, Hiroshi Kuroda, Shuhei Nishiyama, Chihiro Suzuki, Yoshiki Takai, Yasuto Itoyama, Kazuo Fujihara, Masashi Aoki

NEUROLOGY　80　2013/02

DOI： 10.1177/1352458512472748 　

ISSN： 0028-3878

eISSN： 1526-632X
Brainstem Manifestations in Neuromyelitis Optica Peer-reviewed

Laurent Kremer, Maureen Mealy, Anu Jacob, Ichiro Nakashima, Philippe Cabre, Sandra Bigi, Friedemann Paul, Sven Jarius, Orhan Aktas, Liene Elsone, Kerry Mutch, Michael Levy, Yoshiki Takai, Nicolas Collongues, Brenda Banwell, Kazuo Fujihara, Jerome De Seze

NEUROLOGY　80　2013/02

ISSN： 0028-3878

eISSN： 1526-632X
Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica Peer-reviewed

Hiroshi Kuroda, Kazuo Fujihara, Rina Takano, Yoshiki Takai, Toshiyuki Takahashi, Tatsuro Misu, Ichiro Nakashima, Shigeru Sato, Yasuto Itoyama, Masashi Aoki

JOURNAL OF NEUROIMMUNOLOGY　254　(1-2)　178-182　2013/01

DOI： 10.1016/j.jneuroim.2012.09.002 　

ISSN： 0165-5728

eISSN： 1872-8421
駆梅療法で脳室周囲の血流低下の改善を認めた神経梅毒の1例

突田健一, 高井良樹, 成川孝一, 鈴木靖士, 齊藤美穂子, 栗原紀子, 渡辺源也

NEUROINFECTION　17　(2)　243-243　2012/10
Publisher: 日本神経感染症学会
ISSN： 1348-2718

eISSN： 2435-2225
TWO CASES OF LUMBOSACRAL MYELORADICULITIS WITH ANTI-AQUAPORIN-4 ANTIBODY Peer-reviewed

Yoshiki Takai, Tatsuro Misu, Ichiro Nakashima, Toshiyuki Takahashi, Yasuto Itoyama, Kazuo Fujihara, Masashi Aoki

NEUROLOGY　79　(17)　1826-1828　2012/10

DOI： 10.1212/WNL.0b013e3182703ff7 　

ISSN： 0028-3878
Two cases of elderly-onset hereditary neuropathy with liability to pressure palsy manifesting bilateral peroneal nerve palsies. International-journal Peer-reviewed

Norihiko Kawaguchi, Naoki Suzuki, Maki Tateyama, Yoshiki Takai, Tatsuro Misu, Ichiro Nakashima, Yasuto Itoyama, Masashi Aoki

Case reports in neurology　4　(3)　149-55　2012/09

DOI： 10.1159/000342132 　

More details Close

Hereditary neuropathy with liability to pressure palsy (HNPP) is characterized by recurrent focal neuropathies, which usually become symptomatic in the second or third decade of life. However, clinical phenotypic heterogeneity among patients with HNPP has recently been reported. Certain patients show polyneuropathy-type diffuse nerve injuries, whereas others remain asymptomatic at older ages. We present two cases of elderly-onset bilateral peroneal nerve palsies with diffuse muscle weakness in the lower limbs and glove-and-stocking type sensory disturbance. Both patients were diagnosed with HNPP by genetic analyses that detected deletions of chromosome 17p11.2 in peripheral myelin protein 22 genes. Their clinical courses suggested that the Japanese sitting style termed 'seiza', a way of sitting on the floor with the lower legs crossed under the thighs, was a precipitating factor for the bilateral peroneal nerve palsies.
Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan Peer-reviewed

Joanna Kitley, M. Isabel Leite, Ichiro Nakashima, Patrick Waters, Benjamin McNeillis, Rachel Brown, Yoshiki Takai, Toshiyuki Takahashi, Tatsuro Misu, Liene Elsone, Mark Woodhall, Jithin George, Mike Boggild, Angela Vincent, Anu Jacob, Kazuo Fujihara, Jacqueline Palace

BRAIN　135　(Pt 6)　1834-1849　2012/06

DOI： 10.1093/brain/aws109 　

ISSN： 0006-8950
Neuromyelitis optica should be classified as an astrocytopathic disease rather than a demyelinating disease

Kazuo Fujihara, Tatsuro Misu, Ichiro Nakashima, Toshiyuki Takahashi, Monika Bradl, Hans Lassmann, Rina Takano, Shuhei Nishiyama, Yoshiki Takai, Chihiro Suzuki, Douglas Sato, Hiroshi Kuroda, Masashi Nakamura, Juichi Fujimori, Koichi Narikawa, Shigeru Sato, Yasuto Itoyama, Masashi Aoki

Clinical and Experimental Neuroimmunology　3　(2)　58-73　2012/05

DOI： 10.1111/j.1759-1961.2012.00030.x 　

eISSN： 1759-1961
Pathological study of subacute autoimmune encephalopathy with anti-AQP4 antibodies in a pregnant woman Peer-reviewed

Hiroaki Yaguchi, Ichiro Yabe, Yoshiki Takai, Tatsuro Misu, Masaaki Matsushima, Toshiyuki Takahashi, Kanako C. Kubota, Sachiko Akimoto, Kazuo Fujihara, Hidenao Sasaki

MULTIPLE SCLEROSIS JOURNAL　18　(5)　683-687　2012/05

DOI： 10.1177/1352458511422928 　

ISSN： 1352-4585
Influence of pregnancy on neuromyelitis optica spectrum disorder Peer-reviewed

W. Kim, S. -H. Kim, I. Nakashima, Y. Takai, K. Fujihara, M. I. Leite, J. Kitley, J. Palace, E. Santos, E. Coutinho, A. M. Silva, Byoung-Joon Kim, Byung-Jo Kim, S. -W. Ahn, H. J. Kim

NEUROLOGY　78　(16)　1264-1267　2012/04

DOI： 10.1212/WNL.0b013e318250d812 　

ISSN： 0028-3878
Seasonal Variation of Relapses in Neuromyelitis Optica Peer-reviewed

Peter Chater-Lea, Joanna Kitley, Liene Elsone, Yoshiki Takai, Anu Jacob, Ichiro Nakashima, M. Isabel Leite, Kazuo Fujihara, Jackie Palace

ANNALS OF NEUROLOGY　72　S111-S112　2012

ISSN： 0364-5134
広範な大脳白質病変を呈するシェーグレン症候群合併Neuromyelitis opticaの神経放射線および病理学的検討

原一洋, 渡辺宏久, 野田智子, 千田譲, 伊藤瑞規, 熱田直樹, 小池春樹, 前澤聡, 加藤省一, 高井良樹, 三須建郎, 高橋利幸, 藤原一男, 祖父江元

臨床神経学　51　(12)　1370-1370　2011/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Pain in neuromyelitis optica and its effect on quality of life: a cross-sectional study. Peer-reviewed

Kanamori Y, Nakashima I, Takai Y, Nishiyama S, Kuroda H, Takahashi T, Kanaoka-Suzuki C, Misu T, Fujihara K, Itoyama Y

Neurology　77　(7)　652-658　2011/08/16

DOI： 10.1212/WNL.0b013e318229e694 　
Astrocyte lesion and secondary demyelination: The lesson from neuromyelitis optica Peer-reviewed

Tatsuro Misu, Hans Lassmann, Yoshiki Takai, Shuhei Nishiyama, Toshiyuki Takahashi, Ichiro Nakashima, Masashi Aoki, Yasuto Itoyama, Kazuo Fujihara

NEUROSCIENCE RESEARCH　71　E53-E54　2011

DOI： 10.1016/j.neures.2011.07.227 　

ISSN： 0168-0102
Painful Tonic Spasm in Neuromyelitis Optica Peer-reviewed

Yoshiki Takai, Ichiro Nakashima, Tatsuro Misu, Kazuo Fujihara, Yasuto Itoyama

NEUROLOGY　74　(9)　A168-A169　2010/03

ISSN： 0028-3878
Pathogenesis of Neuromyelitis Optica: Aquaporin 4 autoimmunity and astrocytopathy Peer-reviewed

Tatsuro Misu, Kazuo Fujihara, Toshiyuki Takahashi, Rina Takano, Shuhei Nishiyama, Yoshiki Takai, Ichiro Nakashima, Shigeru Sato, Hans Lassmann, Yasuto Itoyama

Clinical Neurology　50　(11)　872　2010

DOI： 10.5692/clinicalneurol.50.872 　

ISSN： 0009-918X
Short Term Efficacy of Thoracoscopic Thymectomy in Senile Onset Myasthenia Gravis Peer-reviewed

Yoshiki Takai, Naoki Suzuki, Ichiro Nakashima, Kazuo Fujihara, Yasuto Itoyama

NEUROLOGY　72　(11)　A54-A54　2009/03

ISSN： 0028-3878
Procalcitonin might help in discrimination between meningeal neuro-Behcet disease and bacterial meningitis. Peer-reviewed

Suzuki N, Mizuno H, Nezu M, Takai Y, Misu T, Kuroda H, Aoki M, Nakashima I, Itoyama Y

Neurology　72　(8)　762-763　2009/02/24

DOI： 10.1212/01.wnl.0000343046.88848.76 　
[Case of Neuro-Behçet disease resembling bacterial meningitis]. Peer-reviewed

Masahiro Nezu, Naoki Suzuki, Hideki Mizuno, Yoshiki Takai, Tatsuro Misu, Masashi Aoki, Ichiro Nakashima, Yasuto Itoyama

Rinsho shinkeigaku = Clinical neurology　48　(10)　750-3　2008/10

DOI： 10.5692/clinicalneurol.48.750 　

ISSN： 0009-918X

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A 30-year-old man with intractable headache and high fever came to the emergency room. He presented skin eruption, aphtha, drowsiness (E3, V4, M6/GCS), meningeal sign, hyperreflexia, and bilateral papilloedema. He also showed pleocytosis (1,066/microl, polymorphonuclear cells predominantly) and pressure increase in CSF. WBC count and CRP were elevated. Two years before, he had meningeal sign, cervical myelitis, skin eruption, uveitis, and aphtha, and was diagnosed as Neuro-BehCet (NBD) disease. HLA-B52 and B55 were positive. We suspected recurrent NBD, but we couldn't exclude bacterial meningitis because of his symptoms and cell-pattern in CSF. We treated him with intravenous methylpredonisolone and antibiotics (MEPM 6 g/day and VCM 2 g/day). His symptoms dramatically improved within a few days. The rapid improvement might be attributed to the steroids. Furthermore, MRI FLAIR images showed multiple small high lesions in the brainstem, hemispheres, subcortical area, putamen and left cerebellar hemisphere. Serum procalcitonin was not increased. We diagnosed the recurrence of NBD retrospectively. Procalcitonin may be a useful marker for discrimination between meningitis due to NBD and septic meningitis.
Clinical Evaluations of Subtotal Thyroidectomy for Graves' Disease

TAKAI Yoshiki

Folia Endocrinologica Japonica　71　(1)　27-38　1995
Publisher: The Japan Endocrine Society
DOI： 10.1507/endocrine1927.71.1_27 　

ISSN： 0029-0661

More details Close

An attempt was made to determine the clinical evaluation of subtotal thyroidectomy in 58 patients with Graves' disease. The weight of the remnant thyroid gland was measured during the operations. Postoperative thyroid volume was measured by ultrasonography (thyroid volume=πabc/6;a is length, b width, and c thickness). Postoperative thyroid function including serum TSH, free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), TSH receptor antibodies (TRAb), and antimicrosomal antibodies (MCHA) was examined. Fifty-eight patients were divided into the three groups, according to postoperative thyroid function;39 (67.2%) in remission, 7 (12.1%) with relapse and 12 (20.7%) in a hypothyroid state. Postoperative thyroid volume in patients with relapse was significantly (p<0.05) greater than that in patients in remission and in a hypothyroid state. Remnant thyroid weight in patients with relapse was significantly (p<0.05) heavier than that in patients in remission and in a hypothyroid state. However, there was no significant difference in an estimated total thyroid weight among the three groups. A significant correlation was noted between the remnant thyroid weight and the postoperative thyroid volume (R=0.58, p<0.001). On the other hand, there was a significant correlation between serum Tg level and the postoperative thyroid volume (R=0.45, p<0.01). Serum level of Tg in patients with relapse was significantly (p<0.05) higher than that in patients in remission and in a hypothyroid state. The prevalence of negative MCHA in patients in remission appeared relatively higher than that in patients with relapse and in a hypothyroid state. In patients with a remnant thyroid weight of less than 4.0g, there was no recurrence following subtotal thyroidectomy, but a higher prevalence of hypothyroid state (43%) was observed compared to those of larger remnant thyroid weight. In patients with a remnant thyroid weight of 4.0 to 6.0g, there was a lower prevalence of recurrence (5.9%) compared to those with a larger remnant thyroid weight, while most patients showed remission (73.5%). On the other hand, the highest prevalence of recurrence (23.5%) was obtained in patients with a remnant thyroid weight of more than 6.0g.<BR>These observations indicate that postopertive thyroid state does not depend upon an estimated total thyroid weight, but depends upon a remnant thyroid weight. In addition, a remnant thyroid weight is closely associated with thyroid volume measured by ultrasonography after subtotal thyroidectomy, which reflected the serum level of Tg.

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Misc. 93

Analysis of CSF complement profile in myelin oligodendrocyte glycoprotein associated disease.

金子仁彦, 黒田宙, 黒田宙, 小野紘彦, 松本勇貴, 松本勇貴, 松本勇貴, 山崎直也, 山本尚輝, 梅澤周, 生田目知尋, 高井良樹, 高橋利幸, 藤盛寿一, 中島一郎, 藤原一男, 藤原一男, 三須建郎, 青木正志

補体　60　(1)　2023

ISSN： 2188-8205
高度の嚥下障害と認知機能低下を認めた若年発症眼咽頭型筋ジストロフィーの1例

大野尭之, 井泉瑠美子, 鈴木直輝, 高井良樹, 小野理佐子, 黒田宙, 割田仁, 竪山真規, 川崎永美子, 鈴木靖士, 青木正志

臨床神経学　62　(5)　409-409　2022/05
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Cases of anti-aquaporin4 antibody-positive neuromyelitis optica spectrum disorder treated with eculizumab initiated immediately after acute treatment

金子仁彦, 浪岡靖弘, 大山綾音, 高井良樹, 檜森紀子, 中澤徹, 三須建郎, 青木正志

神経治療学(Web)　39　(4)　2022

ISSN： 2189-7824
SARS-CoV-2ワクチン後免疫性神経疾患の臨床的特徴と予後

金子仁彦, 松本勇貴, 藤盛寿一, 生田目千尋, 高井良樹, 中島一郎, 三須建郎, 青木正志

Neuroinfection (Web)　27　(2)　2022

ISSN： 2435-2225
神経免疫疾患のエビデンスに基づく診断基準・重症度分類・ガイドラインの妥当性と患者QOLの検証抗MOG抗体関連疾患と抗AQP4陽性視神経脊髄炎の頭部MRI画像における病変分布の比較検討

藤原一男, 松本勇貴, 三須建郎, 麦倉俊司, 高井良樹, 西山修平, 黒田宙, 高橋利幸, 藤盛寿一, 中島一郎, 青木正志

神経免疫疾患のエビデンスに基づく診断基準・重症度分類・ガイドラインの妥当性と患者QOLの検証令和2年度総括・分担研究報告書(Web)　2021
当院におけるサトラリズマブの使用経験

松本勇貴, 三須建郎, 小野紘彦, 高井良樹, 藤原一男, 藤原一男, 青木正志

神経治療学(Web)　38　(6)　2021

ISSN： 2189-7824
治療抵抗性の重症抗MOG抗体関連疾患に対するリツキシマブの使用経験

松本勇貴, 三須建郎, 高井良樹, 西山修平, 小野紘彦, 黒田宙, 割田仁, 青木正志, 黒澤和大, 清水洋, 藤原一男

神経治療学　36　(6)　S288-S288　2019/10
Publisher: (一社)日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
臨床ケース神経ベーチェット病に類似した症候を呈した抗MOG抗体陽性脳炎の2例

藤盛寿一, 高橋利幸, 松本勇貴, 藤原一男, 高井良樹, 三須建郎, 中島一郎

神経免疫学　24　(1)　114-114　2019/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
脳生検により炎症性脱髄性疾患である可能性が示唆された嗜眠性脳炎の1例

大野尭之, 高井良樹, 鈴木直輝, 菅野直人, 小野理佐子, 黒田宙, 勝木将人, 西嶌泰生, 新妻邦泰, 渡辺みか, 神林崇, 青木正志

臨床神経学　59　(7)　477-477　2019/07
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
脳生検により炎症性脱髄性疾患である可能性が示唆された嗜眠性脳炎の1例

大野尭之, 高井良樹, 鈴木直輝, 菅野直人, 小野理佐子, 黒田宙, 勝木将人, 西嶌泰生, 新妻邦泰, 渡辺みか, 神林崇, 青木正志

臨床神経学(Web)　59　(7)　2019

ISSN： 1882-0654
髄液単クローン性免疫グロブリン症を呈したリンパ形質細胞性リンパ腫によるradiculoplexopathyの一例

石山駿, 生田目知尋, 高井良樹, 黒田宙, 割田仁, 青木正志

臨床神経学　58　(1)　72-72　2018/01
Publisher: (一社)日本神経学会
ISSN： 0009-918X
視神経脊髄炎関連疾患に対する経口ステロイド維持療法の最適化

高井良樹, 中島一郎, 三須建郎, 黒田宙, 西山修平, 高橋利幸, 藤原一男, 青木正志

神経治療学　34　(6)　S221-S221　2017/11
Publisher: 日本神経治療学会
ISSN： 0916-8443
Clinical, MRI and laboratory features of myelin oligodendrocyte glycoprotein (MOG)-antibody-associated neurologic disease: a study of 259 cases

K. Kaneko, D. K. Sato, T. Takahashi, R. Ogawa, T. Akaishi, Y. Takai, S. Nishiyama, T. Misu, H. Kuroda, I. Nakashima, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　23　100-100　2017/10

ISSN： 1352-4585

eISSN： 1477-0970
Cerebrospilnal fluid-Actin related protein 2/3 complex subunit 4 as an astrocytic foot process damage marker of aquaporin-4-IgG positive neuromyelitis optica spectrum disorders

S. Nishiyama, T. Misu, I. Nakashima, D. K. Sato, K. Kaneko, R. Ogawa, Y. Takai, T. Toshiyuki, H. Kuroda, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　23　585-585　2017/10

ISSN： 1352-4585

eISSN： 1477-0970
The staging of astrocytopathy in neuromyelitis optica spectrum disorders with aquaporin4-IgG

Y. Takai, T. Misu, H. Suzuki, R. Ogawa, K. Kaneko, S. Nishiyama, H. Kuroda, T. Takahashi, I. Nakashima, K. Fujihara, A. Masashi

MULTIPLE SCLEROSIS JOURNAL　23　27-28　2017/10

ISSN： 1352-4585

eISSN： 1477-0970
Autoimmune encephalitis in patients with anti-myelin oligodendrocyte glycoprotein-antibody

R. Ogawa, I. Nakashima, T. Takahashi, K. Kaneko, T. Akaishi, Y. Takai, D. K. Sato, S. Nishiyama, J. Fujimori, T. Misu, H. Kuroda, T. Ikeda, A. Uchibori, T. Ohashi, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　23　439-440　2017/10

ISSN： 1352-4585

eISSN： 1477-0970
抗MOG抗体陽性脱髄疾患の調査報告国内259例の抗MOG抗体陽性例の臨床的特徴

金子仁彦, 佐藤ダグラス, 高橋利幸, 赤石哲也, 小川諒, 高井良樹, 西山修平, 三須建郎, 中島一郎, 藤原一男, 青木正志

神経免疫学　22　(1)　87-87　2017/10
Publisher: 日本神経免疫学会
ISSN： 0918-936X
肥厚性硬膜炎・自己免疫疾患・膠原病神経サルコイドーシスおよび神経悪性リンパ腫の髄液サイトカインプロファイル

黒田宙, 金子公彦, 中村貴彬, 高井良樹, 藤原一男, 青木正志

神経免疫学　22　(1)　91-91　2017/10
Publisher: 日本神経免疫学会
ISSN： 0918-936X
MS・NMO1 視神経脊髄炎関連疾患病変におけるアストロサイトパチーによる病期分類

高井良樹, 三須建郎, 鈴木博義, 高橋利幸, 西山修平, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経免疫学　22　(1)　97-97　2017/10
Publisher: 日本神経免疫学会
ISSN： 0918-936X
急性脳炎・脳症抗MOG抗体陽性自己免疫性脳炎の検討

小川諒, 中島一郎, 高橋利幸, 金子仁彦, 高井良樹, 藤盛寿一, 三須建郎, 黒田宙, 藤原一男, 青木正志

神経免疫学　22　(1)　104-104　2017/10
Publisher: 日本神経免疫学会
ISSN： 0918-936X
炎症性中枢神経疾患における髄液多形核白血球増多例の検討

黒田宙, 金子公彦, 高井良樹, 藤原一男, 青木正志

NEUROINFECTION　22　(2)　238-238　2017/09
Publisher: 日本神経感染症学会
ISSN： 1348-2718
Discrimination of spinal cord sarcoidosis from neuromyelitis optica spectrum disorder or spondylotic myelopathy

H. Kuroda, T. Takahashi, D. Sato, Y. Takai, S. Nishiyama, T. Misu, I. Nakashima, K. Fujihara, M. Aoki

EUROPEAN JOURNAL OF NEUROLOGY　24　113-113　2017/07

ISSN： 1351-5101

eISSN： 1468-1331
多核球優位の細胞増多を呈し、神経ベーチェット病との鑑別を要した悪性リンパ腫の一例

中村貴彬, 高井良樹, 黒田宙, 三須建郎, 青木正志

臨床神経学　57　(6)　353-353　2017/06
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
抗MOG抗体陽性脱髄疾患におけるIFNβの有効性

金子仁彦, 佐藤ダグラス, 小川諒, 赤石哲也, 高井良樹, 西山修平, 高橋利幸, 三須建郎, 黒田宙, 中島一郎, 藤原一男, 青木正志

脳と発達　49　(Suppl.)　S306-S306　2017/05
Publisher: (一社)日本小児神経学会
ISSN： 0029-0831
抗MOG抗体陽性脱髄疾患におけるIFNβの有効性

金子仁彦, 佐藤ダグラス, 小川諒, 赤石哲也, 高井良樹, 西山修平, 高橋利幸, 三須建郎, 黒田宙, 中島一郎, 藤原一男, 青木正志

脳と発達　49　(Suppl.)　S306-S306　2017/05
Publisher: (一社)日本小児神経学会
ISSN： 0029-0831

eISSN： 1884-7668
Cytokine/Chemokine Profile in MOG-Ab plus Disorder

K. Kaneko, D. K. Sato, R. Ogawa, T. Akaishi, Y. Takai, S. Nishiyama, T. Takahashi, T. Misu, H. Kuroda, S. Tanaka, Nakashima, I, K. Nomura, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　23　(2)　318-318　2017/02

ISSN： 1352-4585

eISSN： 1477-0970
Hypoxia-like Tissue Injury and Glial Response Contribute to the Development of Balo's Concentric Demyelination

Y. Takai, T. Misu, S. Nishiyama, H. Ono, H. Kuroda, I. Nakashima, R. Saito, M. Kanamori, S. Mugikura, M. Watanabe, M. Aoki, K. Fujihara

MULTIPLE SCLEROSIS JOURNAL　23　(2)　349-350　2017/02

ISSN： 1352-4585

eISSN： 1477-0970
多核球優位の細胞増多を呈し,神経ベーチェット病との鑑別を要した悪性リンパ腫の一例

中村貴彬, 高井良樹, 黒田宙, 三須建郎, 青木正志

臨床神経学(Web)　57　(6)　2017

ISSN： 1882-0654
エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立に関する研究抗MOG抗体陽性例における免疫病態解析

藤原一男, 藤原一男, 金子仁彦, 佐藤ダグラス, 佐藤ダグラス, 小川諒, 赤石哲也, 西山修平, 高井良樹, 三須建郎, 高橋利幸, 高橋利幸, 黒田宙, 中島一郎, 青木正志

エビデンスに基づいた神経免疫疾患の早期診断基準・重症度分類・治療アルゴリズムの確立平成28年度総括・分担研究報告書(Web)　41‐42 (WEB ONLY)　2017
抗MOG抗体陽性例の髄液サイトカインの解析

金子仁彦, 佐藤ダグラス, 小川諒, 田中覚, 高井良樹, 西山修平, 三須建郎, 高橋利幸, 黒田宙, 中島一郎, 野村恭一, 藤原一男, 青木正志

神経治療学　33　(5)　S252-S252　2016/10
Publisher: 日本神経治療学会
ISSN： 0916-8443

eISSN： 2189-7824
Temporal changes of pathological features in NMO spectrum disorders with aquaporin4 antibody

Y. Takai, T. Misu, I. Nakashima, H. Kuroda, T. Takahashi, S. Nishiyama, K. Kaneko, T. Akaishi, R. Ogawa, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　22　156-157　2016/09

ISSN： 1352-4585

eISSN： 1477-0970
Pro-inflammatory cytokine elevation in MOG-Ab+, AQP4-Ab+ disorder and MS

K. Kaneko, D. K. Sato, R. Ogawa, T. Akaishi, Y. Takai, S. Nishiyama, T. Takahashi, T. Misu, H. Kuroda, S. Tanaka, I. Nakashima, K. Nomura, D. Callegaro, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　22　155-156　2016/09

ISSN： 1352-4585

eISSN： 1477-0970
Adult MOG-IgG-positive, benign, unilateral, cerebral cortical encephalitis with epileptic seizure

R. Ogawa, I. Nakashima, T. Takahashi, H. Ono, K. Kaneko, T. Akaishi, K. Kurosawa, Y. Takai, D. K. Sato, S. Nishiyama, T. Misu, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　22　711-711　2016/09

ISSN： 1352-4585

eISSN： 1477-0970
Severely exacerbated neuromyelitis optica rat model with extensive tissue damage including astrocytopathy and axonal damage by high affinity anti-aquaporin-4 monoclonal antibody

K. Kurosawa, T. Misu, Y. Takai, D. K. Sato, T. Takahashi, Y. Abe, H. Iwanari, R. Ogawa, I. Nakashima, K. Fujihara, T. Hamakubo, M. Yasui, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　22　160-161　2016/09

ISSN： 1352-4585

eISSN： 1477-0970
けいれんを伴う成人の抗MOG抗体陽性、良性、片側性、大脳皮質性脳炎

小川諒, 中島一郎, 高橋利幸, 金子仁彦, 高井良樹, 佐藤ダグラス, 三須建郎, 黒田宙, 藤原一男, 青木正志

神経免疫学　21　(1)　106-106　2016/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
Balo病における同心円状脱髄病巣形成に対する虚血性組織障害とグリア細胞の関与

高井良樹, 三須建郎, 西山修平, 黒田宙, 中島一郎, 斎藤竜太, 金森政之, 渡辺みか, 青木正志, 藤原一男

神経免疫学　21　(1)　121-121　2016/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
抗MOG抗体陽性脱髄疾患の多数の急性期髄液におけるサイトカインの解析

金子仁彦, 佐藤ダグラス, 小川諒, 高井良樹, 西山修平, 三須建郎, 高橋利幸, 黒田宙, 中島一郎, 藤原一男, 青木正志

神経免疫学　21　(1)　122-122　2016/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
葉酸欠乏症の関与が疑われた脊髄長大病変の1例

原田龍平, 渡辺源也, 高井良樹, 鈴木直輝, 黒田宙, 割田仁, 青木正志

臨床神経学　56　(8)　585-585　2016/08
Publisher: (一社)日本神経学会
ISSN： 0009-918X
片側性の筋萎縮、筋力低下から糖尿病性筋萎縮症の診断に至った1例

菅原裕人, 鴇田藍, 小松恒太郎, 川田健太, 高井良樹, 黒田宙, 澤田正二郎, 今井淳太, 山田哲也, 片桐秀樹

糖尿病　59　(2)　144-144　2016/02
Publisher: (一社)日本糖尿病学会
ISSN： 0021-437X
階段状の症状増悪をきたした頸肋による胸郭出口症候群の1例

戸恒智子, 澁井彩, 高井良樹, 三須建郎, 黒田宙, 青木正志

臨床神経学　55　(12)　951-951　2015/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
リルゾールによる薬剤性間質性肺炎をきたした筋萎縮性側索硬化症

澁井彩, 高井良樹, 小林潤平, 黒田宙, 鈴木直輝, 割田仁, 青木正志

神経治療学　32　(5)　822　2015/09/25

ISSN： 0916-8443
Cerebrospinal fluid lactic dehydrogenation enzyme levels in acute attacks of inflammatory demyelinating diseases

S. Nishiyama, T. Misu, Y. Takai, R. Takano, T. Takahashi, I. Nakashima, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　21　352-352　2015/09

ISSN： 1352-4585

eISSN： 1477-0970
Astrocyte injury and secondary demyelination induced by intracerebral injection of AQP4-IgG and complement in mouse brain

Y. Takai, T. Misu, Y. Abe, K. Kurosawa, T. Takahashi, H. Kuroda, I. Nakashima, S. Nishiyama, D. Sato, M. Yasui, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　21　426-426　2015/09

ISSN： 1352-4585

eISSN： 1477-0970
抗AQP4モノクローナル抗体を用量段階的に投与したpassive IgG transfer NMO rat modelの病理組織学的検討

黒澤和大, 三須建郎, 阿部陽一郎, 高井良樹, 高橋利幸, 佐藤ダグラス, 中島一郎, 藤原一男, 安井正人, 青木正志

神経免疫学　20　(1)　123-123　2015/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
MS基礎 NMOモデルマウスにおけるアストロサイト障害に伴う二次性脱髄機序の解明

高井良樹, 三須建郎, 黒沢和大, 高橋利幸, 中島一郎, 黒田宙, 西山修平, 藤原一男, 青木正志

神経免疫学　20　(1)　96-96　2015/09
Publisher: 日本神経免疫学会
ISSN： 0918-936X
Binding Properties of Anti-AQP4 Antibodies Influencing Endocytosis of AQP4 and Complement-Dependent Cytotoxicity

Yoshiki Takai

MULTIPLE SCLEROSIS JOURNAL　21　(6)　830-830　2015/05

ISSN： 1352-4585

eISSN： 1477-0970
炎症性脱髄性疾患の診断予後における髄液中GFAP濃度有用性の多施設検討サブ解析結果

西山修平, 三須建郎, 清水優子, 横山和正, 景山卓, 高井良樹, 高野里奈, 高橋利幸, 藤盛寿一, 佐藤滋, 中島一郎, 糸山泰人, 藤原一男, 青木正志

臨床神経学　54　(Suppl.)　S151-S151　2014/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Subanalysis of a multicentric cross-sectional study of CSF-GFAP in the diagnosis of inflammatory demyelinating diseases

S. Nishiyama, T. Misu, Y. Shimizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　20　187-188　2014/09

ISSN： 1352-4585

eISSN： 1477-0970
自己抗体研究の新たな展開(第10回) 視神経脊髄炎抗アクアポリン4抗体

高井良樹, 三須建郎, 高橋利幸, 中島一郎, 藤原一男

分子リウマチ治療　7　(3)　112-115　2014/07
Publisher: (株)先端医学社
ISSN： 1882-9163
A Multicenter, Cross-Sectional Study of the Usefulness of CSF-GFAP in the Diagnosis and the Prognosis of Inflammatory CNS Diseases

S. Nishiyama, T. Misu, Y. Simizu, K. Yokoyama, T. Kageyama, Y. Takai, R. Takano, T. Takahashi, J. Fujimori, S. Sato, I. Nakashima, Y. Itoyama, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　20　(7)　911-911　2014/06

ISSN： 1352-4585

eISSN： 1477-0970
Impact Of The Great East Japan Earthquake In 2011 On MS And NMO: A Study In Sendai, Japan

K. Fujihara, Y. Kanamori, Nakashima, I, Y. Takai, D. K. Sato, T. Misu, S. Sato, J. Fujimori, J. Higuchi, H. Kuroda, Y. Itoyama, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　20　(7)　914-914　2014/06

ISSN： 1352-4585

eISSN： 1477-0970
視神経炎にて再発した自己免疫性脳炎の1例

佐藤広隆, 藤盛寿一, 小林理子, 石垣あや, 丹治宏明, 高井良樹, 鈴木直輝, 中島一郎

臨床神経学　54　(3)　242　2014/03/01

ISSN： 0009-918X
Binding properties of monoclonal antibodies against the extracellular domains of mouse aquaporin-4 that influence endocytosis of aquaporin-4 and complement-dependent cytotoxicity

Ping Huang, Yoshiki Takai, Yoichiro Abe, Osamu Arai, Hiroko Iwanari, Julia Ramadhanti, Takayuki Miyauchi, Wakami Goda, Manae Imamura, Mizuki Okada, Kaori Miyazaki, Toshiko Sakihama, Takao Hamakubo, Kazuo Fujihara, Masato Yasui

JOURNAL OF PHARMACOLOGICAL SCIENCES　124　237P-237P　2014

ISSN： 1347-8613

eISSN： 1347-8648
炎症性脱髄性疾患の診断・予後における脳脊髄液中GFAP濃度有用性の多施設横断的検討

西山修平, 三須建郎, 清水優子, 横山和正, 景山卓, 高井良樹, 高野里菜, 高橋利幸, 藤盛寿一, 佐藤滋, 中島一郎, 糸山泰人, 藤原一男, 青木正志

臨床神経学　53　(12)　1461-1461　2013/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
視神経脊髄炎におけるアストロサイトパチー病変とアクアポリン1の関係

三須建郎, 藤原一男, 高井良樹, 西山修平, 中島一郎, 今野秀彦, 糸山泰人, 青木正志

臨床神経学　53　(12)　1530-1530　2013/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
東日本大震災における多発性硬化症および視神経脊髄炎への影響に関するアンケート調査

中島一郎, 金森洋子, 高井良樹, 佐藤滋, 藤盛寿一, 樋口じゅん, 三須建郎, 黒田宙, 藤原一男, 青木正志

臨床神経学　53　(12)　1589-1589　2013/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Diverse mechanisms of tissue injury in neuromyelitis optica

T. Misu, R. Hoeftberger, K. Fujihara, I. Wimmer, Y. Takai, S. Nishiyama, I. Nakashima, H. Konno, M. Bradl, F. Garzuly, Y. Itoyama, M. Aoki, H. Lassmann

MULTIPLE SCLEROSIS JOURNAL　19　(11)　128-128　2013/10

ISSN： 1352-4585

eISSN： 1477-0970
【Antibody Update】 NMO関連疾患と抗AQP4抗体

高井良樹, 三須建郎, 高橋利幸, 中島一郎, 藤原一男

BRAIN and NERVE: 神経研究の進歩　65　(4)　333-343　2013/04
Publisher: (株)医学書院
ISSN： 1881-6096

eISSN： 1344-8129
Clinical Features of Japanese Patients with Myasthenia Gravis Associated with Autoimmune Thyroid Diseases

Genya Watanabe, Yasushi Suzuki, Yoshiki Takai, Kenichi Tsukita, Koichi Narikawa, Kazuo Fujihara

NEUROLOGY　80　2013/02

ISSN： 0028-3878

eISSN： 1526-632X
【内科疾患と関連する認知症〜treatable dementiaを見逃さないために】《内科で見逃せないtreatable dementia》悪性腫瘍に関連する認知機能障害

高井良樹, 青木正志

Modern Physician　33　(1)　38-42　2013/01
Publisher: (株)新興医学出版社
ISSN： 0913-7963
免疫性神経疾患に関する調査研究多発性硬化症/視神経脊髄炎調査東日本大震災における多発性硬化症および視神経脊髄炎への影響についてのアンケート調査

藤原一男, 中島一郎, 金森洋子, 高井良樹, サトウダグラス, 三須建郎, 佐藤滋, 藤盛寿一, 樋口じゅん, 黒田宙

免疫性神経疾患に関する調査研究平成24年度総括・分担研究報告書　2013
免疫性神経疾患に関する調査研究多発性硬化症/視神経脊髄炎臨床(2)炎症性脱髄性疾患の診断における髄液中GFAP濃度有用性の多施設横断的検討

藤原一男, 藤原一男, 三須建郎, 三須建郎, 西山修平, 清水優子, 横山和正, 景山卓, 高井良樹, 高野里菜, 高橋利幸, 藤盛寿一, 佐藤滋, 中島一郎, 糸山泰人, 青木正志

免疫性神経疾患に関する調査研究平成24年度総括・分担研究報告書　2013
NMOにおける非中枢神経系病変

三須建郎, 高井良樹, 高橋利幸, 中島一郎, 糸山泰人, 藤原一男, 青木正志

臨床神経学　52　(12)　1454-1454　2012/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
腫瘍様炎症性脱髄性疾患におけるアストロサイト破壊性病巣

高井良樹, 三須建郎, 小林正樹, 渡邉みか, 中島一郎, 清水優子, 糸山泰人, 藤原一男, 青木正志

臨床神経学　52　(12)　1552-1552　2012/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Brainstem manifestations in neuromyelitis optica

L. Kremer, M. Mealy, A. Jacob, I. Nakashima, P. Cabre, S. Bigi, P. Friedemann, S. Jarius, O. Aktas, M. Levy, Y. Takai, N. Collongues, B. Banwell, K. Fujihara, J. de Seze

MULTIPLE SCLEROSIS JOURNAL　18　292-293　2012/10

ISSN： 1352-4585

eISSN： 1477-0970
PATHOLOGICAL FEATURES OF AQUAPORIN-4 AUTOIMMUNITY WITH CYTOTOXIC EDEMA: THE LESSON FROM NEUROMYELITIS OPTICA AND RELATED DISORDERS

T. Misu, Y. Takai, H. Lassmann, I. Nakashima, Y. Itoyama, M. Aoki, K. Fujihara

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH　36　46A-46A　2012/09

ISSN： 0145-6008
脊髄円錐・馬尾に病変を認めた抗アクアポリン4抗体陽性視神経脊髄炎の2症例

高井良樹, 三須建郎, 中島一郎, 高橋利幸, 鈴木靖士, 糸山泰人, 藤原一男, 青木正志

日本神経免疫学会学術集会抄録集　24回　127-127　2012/09
Publisher: 日本神経免疫学会
【脊髄疾患の新しい話題】視神経脊髄炎における脊髄病変

高井良樹, 三須建郎, 高橋利幸, 中島一郎, 藤原一男

神経内科　77　(1)　49-57　2012/07
Publisher: (有)科学評論社
ISSN： 0386-9709
【NMO spectrumとAQP4の病態意義】 NMOにおけるAQP4の病態意義

高井良樹, 三須建郎, 高崎利幸, 中島一郎, 藤原一男

神経内科　76　(6)　543-548　2012/06
Publisher: (有)科学評論社
ISSN： 0386-9709
Evaluation of the Health-related Quality of Life in NMO

Y. Kanamori, Nakashima, I, Y. Takai, S. Nishiyama, H. Kuroda, T. Takahashi, C. Kanaoka-Suzuki, T. Misu, K. Fujihara, Y. Itoyama

MULTIPLE SCLEROSIS JOURNAL　18　(4)　539-539　2012/04

ISSN： 1352-4585
Aquaporin-4 antibody-positive Male Patients: A Study of 151 Cases from Japan

D. K. Sato, T. Takahashi, Nakashima, I, T. Misu, C. Kanaoka-Suzuki, Y. Kanamori, Y. Takai, S. Nishiyama, H. Kuroda, Y. Itoyama, K. Fujihara, M. Aoki

MULTIPLE SCLEROSIS JOURNAL　18　(4)　527-527　2012/04

ISSN： 1352-4585
DIFFERENCES IN OUTCOMES IN NEUROMYELITIS OPTICA BETWEEN A JAPANESE COHORT AND A PREDOMINANTLY CAUCASIAN COHORT FROM THE UK

J. Kitley, M. I. Leite, P. Waters, B. McNeillis, R. Brown, Y. Takai, A. Jacob, M. Boggild, I. Nakashima, A. Vincent, J. Palace

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY　83　(3)　2012/03

DOI： 10.1136/jnnp-2011-301993.180 　

ISSN： 0022-3050
アストロサイトパチーと二次性脱髄に関する実験的・病理学的検証

三須建郎, Lassmann Hans, 高井良樹, 西山修平, 高橋利幸, 中島一郎, 藤原一男, 糸山泰人

臨床神経学　51　(12)　1207-1207　2011/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
視神経脊髄炎における痛みの評価とQOLに対する影響

中島一郎, 金森洋子, 高井良樹, 西山修平, 鈴木千尋, 三須建郎, 藤原一男, 糸山泰人

臨床神経学　51　(12)　1314-1314　2011/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
脊髄円錐・馬尾に病変を認めた抗アクアポリン4抗体陽性視神経脊髄炎の2症例

高井良樹, 三須建郎, 中島一郎, 高橋利幸, 小林篤史, 北本哲之, 藤原一男, 糸山泰人

臨床神経学　51　(12)　1449-1449　2011/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Two cases of lumbosacral myeloradiculitis with anti aquaporin-4 antibody

Y. Takai, T. Misu, I. Nakashima, M. Aoki, K. Fujihara

MULTIPLE SCLEROSIS JOURNAL　17　S237-S238　2011/10

ISSN： 1352-4585

eISSN： 1477-0970
Histopathological examination of astrocytopathy in tumefactive inflammatory diseases

T. Misu, Y. Takai, M. Watanabe, I. Nakashima, Y. Itoyama, M. Aoki, K. Fujihara

MULTIPLE SCLEROSIS JOURNAL　17　S289-S290　2011/10

ISSN： 1352-4585

eISSN： 1477-0970
Prognostic factors in aquaporin-4 antibody-mediated disease: UK and Japanese cohorts

J. Kitley, M. -I. Leite, P. Waters, B. McNeillis, R. Brown, Y. Takai, M. Boggild, A. Jacob, I. Nakashima, A. Vincent, J. Palace

MULTIPLE SCLEROSIS JOURNAL　17　S291-S291　2011/10

ISSN： 1352-4585

eISSN： 1477-0970
NMO-2 腫瘍様炎症性脱髄性疾患におけるアストロサイト障害の検討

高井良樹, 三須建郎, 中島一郎, 渡邉みか, 青木正志, 藤原一男

日本神経免疫学会学術集会抄録集　23回　91-91　2011/09
Publisher: 日本神経免疫学会
視神経脊髄炎における経口ステロイド剤の再発予防効果

高井良樹, 中島一郎, 高橋利幸, 三須建郎, 藤原一男, 糸山泰人

臨床神経学　50　(12)　1139-1139　2010/12
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Evaluation of characteristic features of pain in neuromyelitis optica and its impact on quality of life

Y. Kanamori, I. Nakashima, Y. Takai, S. Nishiyama, H. Kuroda, T. Takahashi, C. Suzuki, T. Misu, K. Fujihara, Y. Itoyama

MULTIPLE SCLEROSIS　16　(10)　1292-1292　2010/10

ISSN： 1352-4585
Effective protocol for NMO attack prevention by oral prednisolone

I. Nakashima, Y. Takai, T. Misu, T. Takahashi, Y. Fujihara, Itoyama

MULTIPLE SCLEROSIS　16　(10)　1294-1294　2010/10

ISSN： 1352-4585
視床失語を呈したtumefactive demyelinating diseaseの1例

加藤量広, 菅野直人, 井泉瑠美子, 馬場徹, 高井良樹, 三須建郎, 鈴木直輝, 長谷川隆文, 中島一郎, 糸山泰人, 園田順彦, 隈部俊宏, 渡辺みか

臨床神経学　50　(8)　597-597　2010/08/01
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Pathogenicity of anti-aquaporin 4 antibody in NMO

65　(6)　1221-1226　2010/06
Publisher: 最新医学社
ISSN： 0370-8241
視神経脊髄炎(Neuromyelitis optica:NMO)に対する再発予防治療

高井良樹, 中島一郎, 藤原一男

神経治療学　27　(3)　382-382　2010/05
Publisher: 日本神経治療学会
ISSN： 0916-8443
【免疫性神経疾患新たな治療戦略に向けて】代表的な中枢神経の自己免疫疾患 Neuromyelitis optica(NMO)の病態と病理 (内科)

高井良樹, 三須建郎, 藤原一男, 糸山泰人

内科　105　(5)　773-777　2010/05
Publisher: 南江堂
ISSN： 0022-1961
MS/NMO 視神経脊髄炎における経口ステロイド剤の再発予防効果

高井良樹, 中島一郎, 高橋利幸, 三須建郎, 藤原一男, 糸山泰人

日本神経免疫学会学術集会抄録集　22回　56-56　2010/03
Publisher: 日本神経免疫学会
Neuromyelitis Optica(NMO) (Current Insights in Neurological Science)

高井良樹, 三須建郎, 藤原一男

Current Insights in Neurological Science　18　(1)　8-9　2010/03
両側外眼筋麻痺で発症した下垂体卒中の1例

高井良樹, 小林理子, 三須建郎, 中島一郎, 糸山泰人, 小川欣一

臨床神経学　49　(8)　502-502　2009/08
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
高齢で発症した遺伝性圧脆弱性ニューロパチーの2例

川口典彦, 鈴木直輝, 竪山真規, 高井良樹, 水野秀紀, 松田基弘, 三須建郎, 中島一郎, 糸山泰人

臨床神経学　49　(8)　504　2009/08/01

ISSN： 0009-918X
高齢発症重症筋無力症における胸腺摘出術の予後の検討

高井良樹, 中島一郎, 鈴木直輝, 藤原一男, 糸山泰人

Neuroimmunol　17　(1)　129　2009/03/01

ISSN： 0918-936X
腎移植後に発症した頭蓋内悪性リンパ腫の1例

高井良樹, 菊池昭夫, 黒田宙, 金森政之, 渡辺みか, 中島一郎, 糸山泰人

臨床神経学　48　(10)　763-763　2008/10
Publisher: (一社)日本神経学会
ISSN： 0009-918X

eISSN： 1882-0654
Sjoegren症候群を合併したCADASILの2例

川口典彦, 高井良樹, 鈴木直輝, 菊池昭夫, 竪山真規, 青木正志, 中島一郎, 糸山泰人

臨床神経学　48　(10)　458　2008/10/01

ISSN： 0009-918X

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Research Projects 4

MOG抗体関連疾患の臨床表現型と重症化に関する分子免疫病理学的解析

高井良樹

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2021/04/01 - 2024/03/31

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MOG (Myelin oligodendrocyte glycoprotein) 抗体関連疾患は、髄鞘最外層に発現するMOGの立体構造を認識するMOG抗体の発見により、近年確立された疾患体系である。しかし、MOG抗体関連疾患の臨床表現型は非常に多様であり、その差異を生む詳細な免疫病態については未解明である。本研究課題は、中枢神経組織を含む臨床検体を用い、MOG抗体関連疾患の病態に重要な関与が示唆されている補体の活性化と、Th17関連の炎症病態を明らかにすることで、臨床表現型および重症化に関わる主要な因子を特定し、適切な治療法を見出すことを目的としている。申請者らは、本研究課題提出時点で、11例のMOG抗体陽性症例から得られた脳生検組織を用い、脱髄の特徴が単一血管周囲性脱髄 (Perivenous demyelination) であること、MOG優位の髄鞘脱落が生じていることなどを見出し、一方で、活性補体沈着は、類似の臨床表現型を持つ抗AQP4抗体陽性視神経脊髄炎（AQP4+NMOSD）症例に比して乏しいことを報告している。この比較研究は、本研究課題においても重要であるが、神経病理組織所見は、その病期によって見え方が大きく異なることから、より適切な病期分類の元に比較が必要と考えられた。そのため、我々はAQP4+NMOSD症例における活性補体の沈着について、アストロサイトパチーの観点から新たな病期分類を行い、活性補体とその分解産物の組織沈着について検討を行った。その結果、補体の活性化が病期毎に明確に異なることを見出しBrain誌に報告した。
Involvement of ischemic tissue injury in inflammatory demyelinating disease and its therapeutic application

Takai Yoshiki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2017/04/01 - 2020/03/31

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The purpose of this study is to elucidate the pathophysiology of inflammatory demyelinating diseases in the central nervous system.We immunohistochemically analysed biopsied brain tissues from 23 patients with inflammatory demyelinating diseases.The brain biopsies were performed between April 1998 and March 2018. Among them, four of which showed extensive necrosis in the center of the demyelinating lesions. Interestingly, in the vessels located at the boundary between the necrotic site and the demyelinating lesion,expression of Toll-like receptor 4 on the vascular endothelium was enhanced, and prominant deposition of Tenascin-C was seen at enlarged perivascular space.These characteristic findings were not found in any other inflammatory demyelinating diseases such as multiple sclerosis, neuromyelitis optica and acute disseminated encephalomyelitis.
Development of new therapy for neuromyelitis optica using its animal models and anti-AQP4 antibodies.

Abe Yoichiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Keio University

2016/04/01 - 2019/03/31

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We planed to establish new animal models for developing new therapy for neuromyelitis optica. In addition, we tried to elucidate a molecular mechanism for endocytosis of aquaporin-4 induced by binding of autoantibody called NMO-IgG. In this process, we found at least three amino-acid sequences responsible for endocytosis, intracellular trafficking, or degradation of aquaporin-4.
Elucidation of demyelination mechanism caused by astrocyte injury

Takai Yoshiki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2015/04/01 - 2017/03/31

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In this study, we focused on two types of different pathology related to astrocytes injury. One is the effect on the myelin sheath caused by destruction and disappearance of astrocytes which typified by neuromyelitis optica spectrum disorders (NMOSD), and the other is a tissue dammage caused by reactive astrocytes seen in multiple sclerosis and other inflammatory demyelinating disease. As a result, the influence of astrocyte destruction itself is limited. On the other hand, we found inflammatory cytokines produced by reactive astrocytes exhibit a special pattern of myelin sheath damage.